INSUMAN 30 - 100 IU/mL Injectable suspension

Зміст інструкції

1. Insuman Rapid 100 IU/ml injectable solution in a vial
   1. What is Insuman Rapid and what is it used for
   2. What you need to know before using Insuman Rapid
   3. How to use Insuman Rapid
   4. Possible side effects
   5. How to store Insuman Rapid
   6. Content of the pack and other information
2. Insuman Rapid 40 UI/ml injectable solution in a vial
   1. What is Insuman Rapid and what is it used for
   2. What you need to know before using Insuman Rapid
   3. How to use Insuman Rapid
   4. Possible side effects
   5. How to store Insuman Rapid
   6. Contents of the pack and other information
3. Insuman Rapid 100 IU/ml injectable solution in a cartridge
   1. What is Insuman Rapid and what is it used for
   2. What you need to know before using Insuman Rapid
   3. How to use Insuman Rapid
   4. Possible side effects
   5. How to store Insuman Rapid
   6. Contents of the pack and other information
4. Insuman Rapid SoloStar 100 UI/ml solution for injection in a pre-filled pen
   1. What is Insuman Rapid and what is it used for
   2. What you need to know before using Insuman Rapid
   3. How to use Insuman Rapid
   4. Possible side effects
   5. How to store Insuman Rapid
   6. Content of the pack and other information
5. Insuman Basal 100 IU/ml injectable suspension in a vial
   1. What is Insuman Basal and what is it used for
   2. What you need to know before using Insuman Basal
   3. How to use Insuman Basal
   4. Possible side effects
   5. How to store Insuman Basal
   6. Content of the pack and other information
6. Insuman Basal 40 UI/ml injectable suspension in a vial
   1. What is Insuman Basal and what is it used for
   2. What you need to know before using Insuman Basal
   3. How to use Insuman Basal
   4. Possible side effects
   5. How to store Insuman Basal
   6. Contents of the pack and other information
7. Insuman Basal 100 IU/ml injectable suspension in a cartridge
   1. What is Insuman Basal and what is it used for
   2. What you need to know before using Insuman Basal
   3. How to use Insuman Basal
   4. Possible side effects
   5. How to store Insuman Basal
   6. Contents of the pack and other information
8. Insuman Basal SoloStar 100 IU/ml injectable suspension in a pre-filled pen
   1. What is Insuman Basal and what is it used for
   2. What you need to know before using Insuman Basal
   3. How to use Insuman Basal
   4. Possible side effects
   5. How to store Insuman Basal
   6. Contents of the pack and other information
9. Insuman Comb 15 100 IU/ml injectable suspension in a vial
   1. What is Insuman Comb 15 and what is it used for
   2. What you need to know before using Insuman Comb 15
   3. How to use Insuman Comb 15
   4. Possible side effects
   5. How to store Insuman Comb 15
   6. Content of the pack and other information
10. Insuman Comb 15 100 IU/ml injectable suspension in a cartridge
    1. What is Insuman Comb 15 and what is it used for
    2. What you need to know before using Insuman Comb 15
    3. How to use Insuman Comb 15
    4. Possible side effects
    5. How to store Insuman Comb 15
    6. Contents of the pack and other information
11. Insuman Comb 15 SoloStar 100 UI/ml injectable suspension in a pre-filled pen
    1. What is Insuman Comb 15 and what it is used for
    2. What you need to know before using Insuman Comb 15
    3. How to use Insuman Comb 15
    4. Possible side effects
    5. How to store Insuman Comb 15
    6. Content of the pack and other information
12. Insuman Comb 25 100 IU/ml injectable suspension in a vial
    1. What is Insuman Comb 25 and what is it used for
    2. What you need to know before using Insuman Comb 25
    3. How to use Insuman Comb 25
    4. Possible side effects
    5. How to store Insuman Comb 25
    6. Content of the pack and other information
13. Insuman Comb 25 40 UI/ml injectable suspension in a vial
    1. What is Insuman Comb 25 and what is it used for
    2. What you need to know before using Insuman Comb 25
    3. How to use Insuman Comb 25
    4. Possible side effects
    5. How to store Insuman Comb 25
    6. Content of the pack and other information
14. Insuman Comb 25 100 UI/ml injectable suspension in a cartridge
    1. What is Insuman Comb 25 and what is it used for
    2. What you need to know before using Insuman Comb 25
    3. How to use Insuman Comb 25
    4. Possible side effects
    5. How to store Insuman Comb 25
    6. Contents of the pack and other information
15. Insuman Comb 25 SoloStar 100 IU/ml injectable suspension in a pre-filled pen
    1. What is Insuman Comb 25 and what is it used for
    2. What you need to know before using Insuman Comb 25
    3. How to use Insuman Comb 25
    4. Possible side effects
    5. How to store Insuman Comb 25
    6. Contents of the pack and other information
16. Insuman Comb 30 100 IU/ml injectable suspension in a vial
    1. What is Insuman Comb 30 and what is it used for
    2. What you need to know before using Insuman Comb 30
    3. How to use Insuman Comb 30
    4. Possible side effects
    5. How to store Insuman Comb 30
    6. Content of the pack and other information
17. Insuman Comb 30 100 IU/ml injectable suspension in a cartridge
    1. What is Insuman Comb 30 and what is it used for
    2. What you need to know before using Insuman Comb 30
    3. How to use Insuman Comb 30
    4. Possible side effects
    5. How to store Insuman Comb 30
    6. Contents of the pack and other information
18. Insuman Comb 30 SoloStar 100 IU/ml injectable suspension in a pre-filled pen
    1. What is Insuman Comb 30 and what it is used for
    2. What you need to know before using Insuman Comb 30
    3. How to use Insuman Comb 30
    4. Possible side effects
    5. How to store Insuman Comb 30
    6. Package contents and other information
19. Insuman Comb 50 100 IU/ml injectable suspension in a vial
    1. What is Insuman Comb 50 and what is it used for
    2. What you need to know before using Insuman Comb 50
    3. How to use Insuman Comb 50
    4. Possible side effects
    5. How to store Insuman Comb 50
    6. Content of the pack and other information
20. Insuman Comb 50 40 UI/ml injectable suspension in a vial
    1. What is Insuman Comb 50 and what is it used for
    2. What you need to know before using Insuman Comb 50
    3. How to use Insuman Comb 50
    4. Possible side effects
    5. How to store Insuman Comb 50
    6. Content of the pack and other information
21. Insuman Comb 50 100 IU/ml injectable suspension in a cartridge
    1. What is Insuman Comb 50 and what is it used for
    2. What you need to know before using Insuman Comb 50
    3. How to use Insuman Comb 50
    4. Possible side effects
    5. How to store Insuman Comb 50
    6. Contents of the pack and other information
22. Insuman Comb 50 SoloStar 100 UI/ml injectable suspension in a pre-filled pen
    1. What is Insuman Comb 50 and what is it used for
    2. What you need to know before using Insuman Comb 50
    3. How to use Insuman Comb 50
    4. Possible side effects
    5. How to store Insuman Comb 50
    6. Contents of the pack and other information
23. Insuman Infusat 100 IU/ml injectable solution in a vial
    1. What is Insuman Infusat and what is it used for
    2. What you need to know before using Insuman Infusat
    3. How to use Insuman Infusat
    4. Possible side effects
    5. How to store Insuman Infusat
    6. Content of the pack and other information
24. Insuman implantable 400 IU/ml infusion solution
    1. What is Insuman Impiantabile and what is it used for
    2. Cosa deve sapere prima di usare Insuman Impiantabile
    3. How to use Insuman Implantable
    4. Possible side effects
    5. How to store Insuman Impiantabile
    6. Contents of the pack and other information

221

Insuman Rapid 100 IU/ml injectable solution in a vial

Human insulin
Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Rapid is and what it is used for
• 2. What you need to know before you use Insuman Rapid
• 3. How to use Insuman Rapid
• 4. Possible side effects
• 5. How to store Insuman Rapid
• 6. Contents of the pack and other information

1. What is Insuman Rapid and what is it used for

Insuman Rapid contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Rapid is a short-acting insulin solution with a short duration of action.
Insuman Rapid is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels. Insuman Rapid can also be
used for the treatment of hyperglycemic coma (coma caused by excessively high blood sugar levels) and ketoacidosis (build-up of acids in the blood because the body is using fats instead of sugar) as well as for blood sugar control before, during and after
surgery.

2. What you need to know before using Insuman Rapid

Do not use Insuman Rapid
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Rapid.
Follow strictly the instructions given to you by your doctor regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
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Special patient groups
If you have problems with your liver or kidneys, or if you are elderly, consult your doctor because you may need a lower
dose.
Changes in the skin at the injection site:
The injection site must be rotated to prevent changes in the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Rapid). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
ask you to check your blood sugar more carefully and adjust the dose of insulin or other medicines
for diabetes.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, diabetes control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will rise (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will drop (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or carbohydrate intake. It is necessary to inform people close to you of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a history of stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Rapid
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, an optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions), 223
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• beta-blockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Beta-blockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Rapid with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, ask your doctor or pharmacist for advice before using this medicine.
Inform your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Rapid in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.

Driving and using machines
The ability to concentrate or react may be reduced in case of:
224

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take into account the possibility that this may occur in all situations where it could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Rapid
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor or pharmacist.
Based on your lifestyle and the results of blood sugar tests (glycaemia), your doctor will:

• establish the daily amount of Insuman Rapid you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Rapid is needed.

Many factors can influence your blood sugar levels. It is advisable that you are aware of these factors so that you can act appropriately in case of changes in blood sugar levels and thus avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Frequency of administration
Insuman Rapid is injected subcutaneously 15 - 20 minutes before a meal.

Method of administration
Insuman Rapid is a solution for subcutaneous injection or, in exceptional cases, intravenously (into a blood vessel).
Your doctor will tell you which area of the skin you should inject the insulin into. For each injection, change the injection site within the chosen area of skin.
The administration of insulin intravenously, for example for the treatment of severe hyperglycaemia or ketoacidosis, requires experience and special safety precautions. For these reasons, this must be done in a hospital or a similar facility.
Do not use Insuman Rapid in insulin pumps - special insulin preparations are available for use with such devices. Also, do not use it in peristaltic pumps with silicone tubing.

How to handle the vials
Insuman Rapid contains 100 IU of insulin per ml. Only syringes suitable for this concentration (100 IU per ml) must be used. Injection syringes must not contain any other medicines or their residues (such as traces of heparin).
Before drawing up the insulin for the first time, you must remove the tear-off safety cap from the vial.
225
Insuman Rapid must only be used if the solution is clear, colourless, without visible solid particles and has a watery consistency.
Do not shake the vial vigorously as this may cause foaming. Foam may interfere with the correct measurement of the dose.

Special precautions before the injection
Air bubbles must be removed before the injection. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix the insulin with other medicines, except for the human insulin formulations listed below.
Insuman Rapid can be mixed with all human insulin formulations, EXCEPT those specifically intended for use in insulin pumps. Also, do not mix with animal insulins or insulin analogues.
Your doctor will tell you if it is necessary to mix human insulins. If a mixture is necessary, draw up Insuman Rapid into the injection syringe before the other insulin. Proceed with the injection immediately after mixing. Do not mix insulins of different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Rapid than you should

• If you have injected too high a dose of Insuman Rapid, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the section at the end of this leaflet.

If you forget to use Insuman Rapid

• If you have forgotten a dose of Insuman Rapidor have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the section at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Rapid
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman Rapid without consulting a doctor who will tell you what you need to do.
If you have any questions about using this medicine, ask your doctor, pharmacist or nurse.

Swapping insulins
You should always check the insulin label before each injection to avoid swapping between Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

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Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulinmay occur, which could be life-threatening. Such reactions to insulin or excipients can cause widespread skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies necessitate an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.
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Do not use this medicine after the expiry date which is stated on the pack and on the vial label after “Scad”/“Exp”. The expiry date refers to the last day of that month.
Unused vials
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Rapid in direct contact with the
freezer compartment or with refrigerant packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials
Once opened, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C, protected from a direct source of heat (e.g. radiator) or from direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to eliminate the
medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Rapid contains

• The active substance is human insulin. 1 ml of Insuman Rapid contains 100 IU (International Units) of the active substance human insulin.
• The other ingredients are: metacresol, dihydrate sodium dihydrogen phosphate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Rapid”), hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Insuman Rapid and contents of the pack
Insuman Rapid is a clear, colourless, injectable solution, similar in appearance to water and free from visible
solid particles.
Insuman Rapid is supplied in vials containing 5 ml of injectable solution (equivalent to 500 IU) or 10
ml of injectable solution (equivalent to 1000 IU). Packs of 1 and 5 vials of 5 ml or
10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany
For further information on this medicine, contact the local representative of the Marketing Authorisation
Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050
228

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Asland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: + +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525
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Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, facial flushing, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do in case of hyperglycemia?
Check your blood sugar and the possible presence of ketones in your
urine as soon as possible if you experience any of the symptoms listed above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, generally in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognize when your blood sugar levels are dropping too low, so you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals, 230
• you are not eating enough or the food consumed contains less carbohydrates than usual (carbohydrates are sugar and sugar-like substances; however artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognizing it in time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more frequent blood sugar checks may help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid all situations (such as driving a car) that could be
risky for you and others due to hypoglycemia.

What should you do in case of hypoglycemia?
231

• 1. Do not inject insulin. Take immediately 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should have discussed these measures with you beforehand.
• 3. If another hypoglycemia occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you realize you are unable to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or if you lose consciousness, an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood glucose immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
232

Insuman Rapid 40 UI/ml injectable solution in a vial

Human insulin
Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Rapid is and what it is used for
• 2. What you need to know before you use Insuman Rapid
• 3. How to use Insuman Rapid
• 4. Possible side effects
• 5. How to store Insuman Rapid
• 6. Contents of the pack and other information

1. What is Insuman Rapid and what is it used for

Insuman Rapid contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Rapid is a rapid-acting, short-duration insulin solution.
Insuman Rapid is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels. Insuman Rapid can also be
used for the treatment of hyperglycemic coma (coma caused by excessively high blood sugar levels) and ketoacidosis (build-up of acids in the blood because the body is using fats instead of sugar) as well as for blood sugar control before, during and after
surgery.

2. What you need to know before using Insuman Rapid

Do not use Insuman Rapid
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Rapid.
Follow the instructions given to you by your doctor strictly regarding the dose, checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special patient groups
If you have problems with your liver or kidneys, or if you are elderly, consult your doctor because you may need a lower
dose.
233
Changes in the skin at the injection site:
The injection site must be rotated to prevent changes in the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Rapid). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic medicines
Travel
Consult your doctor before starting a trip. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, diabetes control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Furthermore, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or carbohydrate intake. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or localized swelling (edema).

Other medicines and Insuman Rapid
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),
• disopyramide (used to treat certain heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),

234

• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely eliminate the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Rapid with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
Inform your doctor if you are planning a pregnancy or are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Rapid in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.

Driving and using machines
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. 235

Take into account the possibility that this may occur in all situations where you could pose a
risk to yourself and others (such as driving a car or using machinery). Ask your
doctor for advice on whether it is appropriate for you to drive if:

• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Rapid
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of blood sugar level tests (glycaemia), your doctor will:

• establish the daily amount of Insuman Rapid you need,
• inform you of when you need to check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Rapid is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these factors so that you can act appropriately in case of changes in blood sugar levels and thus avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Frequency of administration
Insuman Rapid is injected subcutaneously 15 - 20 minutes before a meal.

Method of administration
Insuman Rapid is a solution for subcutaneous injection or, in exceptional cases, intravenously (blood vessel).
Your doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site within the chosen area of skin.
The administration of insulin intravenously, for example for the treatment of severe hyperglycaemia or
ketoacidosis, requires experience and special safety precautions. For these reasons, this must be done
in a hospital or similar facility.
Do not use Insuman Rapid in insulin pumps - special insulin preparations are available for use with such devices.
Also, do not use it in peristaltic pumps with silicone tubing.

How to handle the vials
Insuman Rapid contains 40 IU of insulin per ml. Only syringes suitable for this concentration (40 IU per ml) must be used. Injection syringes must not contain other medicines or their residues (such as traces of heparin).
Before drawing up the insulin for the first time, remove the tear-off safety cap from the vial.
236
Insuman Rapid must only be used if the solution is clear, colourless, without visible solid particles and has a watery consistency.
Do not shake the vial vigorously as this may cause foaming. Foam may interfere with accurate dose measurement.

Special precautions before injection
Air bubbles must be removed before injection. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix the insulin with other medicines, except for the human insulin formulations listed below.
Insuman Rapid can be mixed with all human insulin formulations, EXCEPT those specifically intended for use in insulin pumps. Also, do not mix with animal insulins or insulin analogues.
Your doctor will tell you if it is necessary to mix human insulins. If a mixture is necessary, draw up Insuman Rapid into the injection syringe before the other insulin. Proceed with the injection immediately after mixing. Do not mix insulins of different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Rapid than you should

• If you have injected too high a dose of Insuman Rapid, blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the section at the end of this leaflet.

If you forget to use Insuman Rapid

• If you have forgotten a dose of Insuman Rapidor have not injected enough insulin, blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the section at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Rapid
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman Rapid without consulting a doctor who will tell you what you need to do.
If you have any questions about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicines between Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)
237

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin may also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well if you inject it into an area with lumps. Change the injection site with each injection to prevent these skin changes
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances may spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the vial label
after “Scad”/“Exp”. The expiry date refers to the last day of that month.
238
Vials not in use
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Rapid in direct contact with the
freezer compartment or with cooling packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials
Once in use, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C away from a direct heat source (e.g. radiator) or direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Rapid contains

• The active substance is human insulin. 1 ml of Insuman Rapid contains 40 IU (International Units) of the active substance human insulin.
• The other ingredients are: meta-cresol, disodium hydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Rapid”), hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Insuman Rapid and contents of the pack
Insuman Rapid is a clear, colourless, injectable solution, similar in appearance to water and without visible solid
particles.
Insuman Rapid is supplied in vials containing 10 ml of solution (400 IU). Packs of 1 and 5 vials of 10 ml are
available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the Marketing Authorisation
Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275
239

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
240
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Rapid”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do in case of hyperglycemia?
Check your blood sugar and the possible presence of ketones in your
urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, generally in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognize when your blood sugar levels are dropping too low, so
you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains less carbohydrates than usual (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity, 241
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, speech difficulties (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), sensations of tingling and numbness in the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin like Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognizing it in time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more frequent blood sugar checks can help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do in case of hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. Then consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should discuss these measures with you in advance.
• 3. If another hypoglycemia occurs, take another 10 to 20 g of sugar.

242

• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, intervention with an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are also justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
243

Insuman Rapid 100 IU/ml injectable solution in a cartridge

Human insulin
Read this leaflet carefully before using this medicine as it contains important
information for you. Instructions for using the insulin pen are provided with your insulin pen.
Refer to these before using your medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Rapid is and what it is used for
• 2. What you need to know before you use Insuman Rapid
• 3. How to use Insuman Rapid
• 4. Possible side effects
• 5. How to store Insuman Rapid
• 6. Contents of the pack and other information

1. What is Insuman Rapid and what is it used for

Insuman Rapid contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Rapid is a rapid-onset and short-acting insulin solution.
Insuman Rapid is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Rapid

Do not use Insuman Rapid
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Rapid in cartridges is only suitable for subcutaneous injections with a reusable pen (see
also section 3). Talk to your doctor if you need to inject the insulin in a different way.
Consult your doctor, pharmacist or nurse before using Insuman Rapid.
Follow the instructions given to you by your doctor strictly regarding the dose, checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
244
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Changes in the skin at the injection site:
The injection site must be rotated to prevent changes in the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Rapid). If you are currently injecting into an area with
nodules, consult your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, diabetes control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Furthermore, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Rapid
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping the use of another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure), 245
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progesterone (such as in the birth control pill used for birth control),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking any of these medicines, ask your doctor or pharmacist.

Insuman Rapid with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before using this medicine.
Inform your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Rapid in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.
246

Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take this into account in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether it is appropriate for you to drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Rapid
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of blood sugar level tests (glycaemia), your doctor will:

• establish the daily amount of Insuman Rapid you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Rapid is needed.

Many factors can influence your blood sugar levels. It is advisable that you are aware of these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Rapid is injected subcutaneously 15 - 20 minutes before a meal.

Method of administration
Insuman Rapid is a solution for subcutaneous injection.
Your doctor will tell you which area of the skin you should inject the insulin into. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Rapid in insulin pumps - special insulin preparations are available for use with such devices.
Also do not use it in peristaltic pumps with silicone tubing.

How to handle the cartridges
Insuman Rapid in cartridges is only suitable for subcutaneous injections with a reusable pen (see
also section 3). Talk to your doctor if you need to inject insulin in another way.
To ensure the administration of the correct dose, Insuman Rapid cartridges must be used
only with the following pens:

• JuniorStar for the administration of Insuman Rapid in dose increments of 0.5 units
• ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO for the administration of Insuman Rapid in dose increments of 1 unit. 247

It is possible that not all pens are marketed in your country.
The pens must be used as recommended in the information provided by the device manufacturer. For loading the cartridge, inserting the injection needle and administering
the insulin injection, carefully follow the manufacturer's instructions for using the pen.
It is recommended to store the cartridge at room temperature for 1 or 2 hours before inserting it into the pen.
Check the cartridge carefully before use. Use it only if the solution is clear, colourless,
without visible solid particles and has a watery consistency.

Particular precautions before injection
Air bubbles must be removed before injection (see the instructions for using the pen).
Make sure that neither alcohol nor other disinfectants nor other contaminating substances come into contact with the insulin.

• Do not refill or reuse empty cartridges.
• Do not add other insulins to the cartridges.
• Do not mix Insuman Rapid with other medicines.

Problems with the pen?
Refer to the manufacturer's instructions for using the pen.
If the insulin pen is damaged or does not function properly (due to mechanical defects) it must be discarded and a new insulin pen must be used.
If you use more Insuman Rapid than you should

• If you have injected too high a dose of Insuman Rapid, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the box
  at the end of this leaflet.

If you forget to use Insuman Rapid

• If you have forgotten a dose of Insuman Rapidor have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Rapid
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up
of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman
Rapid without consulting a doctor who will tell you what is necessary to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicines between
Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
248
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most common side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For more information about the side effects of low or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Changes in the skin at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site, or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.
249

5. How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the cartridge label
after “Scad”/“Exp”. The expiry date refers to the last day of that month.
Unused cartridges
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Rapid in direct contact with the
freezer compartment or with refrigerant packs. Store the cartridge in the outer packaging to
protect the medicine from light.
Cartridges in use
Cartridges in use (in the insulin pen) or kept as “spare”, can be stored for a maximum
of 4 weeks at a temperature not exceeding 25°C, protected from a source of direct heat (e.g.
radiator) or direct light (direct sunlight or lamp). The cartridge in use must not be stored in
the refrigerator. Do not use the cartridge after this period.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Rapid contains

• The active ingredient is human insulin. 1 ml of Insuman Rapid contains 100 IU (International Units) of the active ingredient human insulin.
• The other ingredients are: metacresol, dihydrate sodium dihydrogen phosphate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Rapid”), hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Insuman Rapid and contents of the pack
Insuman Rapid is a clear, colourless injectable solution, similar in appearance to water and without visible
solid particles.
Insuman Rapid is supplied in cartridges containing 3 ml of solution (300 IU). Packs containing
3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany
For further information on this medicinal product, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)
250

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Asland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525
251

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCAEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycaemia),you may not have injected enough
insulin.

Why does hyperglycaemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• the insulin pen is not working correctly,
• you are doing less physical exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

Warning signs of hyperglycaemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine. Abdominal
pain, deep and rapid breathing, drowsiness or even loss of consciousness may indicate a
serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do in case of hyperglycaemia?
Check your blood sugar and the presence of ketones in your urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycaemia or ketoacidosis must
always be treated by a doctor, generally in a hospital setting.

HYPOGLYCAEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycaemic episodes
can cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognise when your blood sugar levels are dropping too low, so that you can
take appropriate precautions.

Why does hypoglycaemia occur?
Examples include:

• you injected too much insulin, 252
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhoea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more physical exercise than usual, or a different type of activity,
• you are recovering from injuries, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

Hypoglycaemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycaemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, speech difficulties (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycaemia ("warning symptoms") may vary, be less
evident or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycaemic episode (e.g. the day before) or if hypoglycaemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Rapid”).

In these cases, a severe hypoglycaemia (even with loss of consciousness) may develop without being
recognised in time. Therefore, learn to recognise the warning signs of hypoglycaemia. If necessary, more
frequent blood sugar checks may be helpful in identifying mild hypoglycaemic episodes that might
otherwise go unnoticed. If you are unable to recognise the warning signs of hypoglycaemia, avoid all
situations (such as driving a car) that may be risky for you and others due to
hypoglycaemia.

What should you do in case of hypoglycaemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help to treat hypoglycaemia.

253

• 2. Then consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should have discussed these measures with you beforehand.
• 3. If another hypoglycaemia occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice that you are unable to control hypoglycaemia or if it occurs again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are also justified if
you are not sure whether a hypoglycaemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm that
a hypoglycaemic episode was occurring.
254

Insuman Rapid SoloStar 100 UI/ml solution for injection in a pre-filled pen

Human insulin

Read this leaflet carefully, including the instructions for use of the Insuman Rapid SoloStar pre-filled pen, before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Rapid is and what it is used for
• 2. What you need to know before you use Insuman Rapid
• 3. How to use Insuman Rapid
• 4. Possible side effects
• 5. How to store Insuman Rapid
• 6. Contents of the pack and other information

1. What is Insuman Rapid and what is it used for

Insuman Rapid contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Rapid is a rapid-acting, short-duration insulin solution. It is presented in
cartridges contained in a disposable SoloStar pen injector.
Insuman Rapid is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Rapid

Do not use Insuman Rapid
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Rapid in pre-filled pen is only suitable for subcutaneous injections (see also section 3).
Talk to your doctor if you need to inject the insulin in a different way.
Contact your doctor, pharmacist or nurse before using Insuman Rapid.
Follow the instructions given to you by your doctor strictly regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise), injection technique.
Tell your doctor if you are allergic to this medicine or to animal insulins.
255
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Skin changes at the injection site:
The injection site must be rotated to prevent skin changes, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject it into an area with
nodules (see section How to use Insuman Rapid). If you are currently injecting into an area with
nodules, contact your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of changing time zones,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, blood sugar control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or carbohydrate intake. It is necessary to inform people close to you of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Rapid
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping the use of another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin-converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure), 256
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase (MAO) inhibitors (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progesterone (as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• beta-blockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Beta-blockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Rapid with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, ask your doctor or
pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Rapid in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the dose of insulin and
diet may be necessary.

Driving and using machines
257
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take this into account in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Rapid
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, ask your doctor or pharmacist.
Based on your lifestyle and the results of blood sugar level tests (glycaemia), your doctor will:

• establish the daily amount of Insuman Rapid you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Rapid is needed.

Many factors can influence your blood sugar levels. It is advisable that you are aware of these factors so that you can act appropriately in case of changes in blood sugar levels and thus avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Frequency of administration
Insuman Rapid is injected subcutaneously 15 - 20 minutes before a meal.

Method of administration
Insuman Rapid is a solution for subcutaneous injection.
SoloStar releases insulin in doses from 1 to 80 units in 1-unit increments. Each pen contains multiple doses.
Your doctor will tell you which area of the skin you should inject the insulin into. For each injection, change the injection site within the chosen area of skin.

How to handle SoloStar
SoloStar is a disposable pre-filled pen containing human insulin. Insuman Rapid in a pre-filled pen is only suitable for subcutaneous injections. Talk to your doctor if you need to inject insulin in another way.

you must use the pen as described in these Instructions for Use.
A new injection needle must be inserted before each use. Use only needles approved for use with SoloStar.
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A safety test must be performed before each injection.
Check the cartridge before using the pen. Do not use Insuman Rapid if you observe particles inside. Use Insuman Rapid only if the solution is clear, colourless and similar to water.
Always use a new pen if you notice that your blood sugar control has unexpectedly worsened. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.
To prevent possible transmission of disease, each pen must be used by only one patient.

Special precautions before injection
Make sure that neither alcohol nor other disinfectants nor other contaminating substances contaminate the insulin.
Do not mix insulin with other medicines. Insuman Rapid Solostar pre-filled pen has not been studied for adding other insulins to the cartridge.
Empty pens should never be reused and must be disposed of properly.
Do not use SoloStar if it is damaged or does not function properly. It must be disposed of and a new SoloStar must be used.

If you use more Insuman Rapid than you should

• If you have injected too high a dose of Insuman Rapid, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the section at the end of this leaflet.

If you forget to use Insuman Rapid

• If you have forgotten a dose of Insuman Rapidor have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the section at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop using Insuman Rapid
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman Rapid without consulting a doctor who will tell you what you need to do.
If you have any questions about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicines between Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock) 259

Side effects reported with unknown frequency(cannot be estimated from available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Changes in the skin at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only in rare cases does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.
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Do not use this medicine after the expiry date that is stated on the pack and on the pen label after “Scad”/“Exp”. The expiry date refers to the last day of that month.
Pens not in use
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place the prefilled pen in direct contact with the freezer compartment or with refrigerant packs. Store the prefilled pen in the outer packaging to protect the medicine from light.
Pens in use
Prefilled pens in use or kept “in reserve” can be stored for a maximum of 4 weeks at a temperature not exceeding 25°C, protected from a source of direct heat (e.g. radiator) or direct light (direct sunlight or lamp). The pen in use must not be stored in a refrigerator. Do not use the pen after this period.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Rapid contains

• The active substance is human insulin. 1 ml of Insuman Rapid contains 100 IU (International Units) of the active substance human insulin.
• The other ingredients are: metacresol, disodium hydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Rapid”), hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Insuman Rapid and content of the pack
Insuman Rapid is a clear, colourless injectable solution, similar in appearance to water and without visible solid
particles.
Insuman Rapid is supplied in pre-filled SoloStar pens, containing 3 ml of solution (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are
available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany
For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050
261

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
262
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• the insulin pen is not working properly,
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Rapid”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, redness of the face, loss of appetite,
low blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do in case of hyperglycemia?
Check your blood sugar and the possible presence of ketones in your
urine as soon as possible if you experience any of the symptoms listed above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognise when your blood sugar levels are dropping too low, so
you can take appropriate precautions.
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Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhoea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Rapid”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin like Insuman,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Rapid”).

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In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognising it in time. Therefore, learn to recognise the warning signs of hypoglycemia. If necessary, more
frequent blood sugar checks may help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognise the warning signs of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do in case of hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. Then consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should discuss these measures with you beforehand.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice that you cannot control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, action must be taken with an injection of glucose or
glucagon (a medicine that increases blood sugar levels). These injections are also justified
even if you are not sure that a hypoglycemic event has occurred.
Blood sugar should be checked immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
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Insuman Rapid SoloStar injectable solution in a pre-filled pen. Instructions for Use.
SoloStar is a pre-filled pen for injecting insulin. Your doctor has decided that SoloStar is suitable for you
based on your ability to use SoloStar. Talk to your doctor, pharmacist or nurse about the correct
injection technique before using SoloStar.
Read these instructions carefully and completely before using your SoloStar. If you are unable to
use SoloStar or follow all the instructions completely on your own, you must only use SoloStar if you can
get help from someone who can follow all the instructions completely. Hold the pen horizontally, with the needle to the left and the dose selector on the right, as shown in the figures
below.

Follow these instructions completely each time you use SoloStar to ensure you take an accurate
dose. If you do not follow these instructions completely, you may take too much or too little insulin, which
can change your blood glucose levels.
Doses from 1 to 80 units can be selected in 1-unit increments. Each pen contains multiple doses.
Keep this leaflet for future reference.
If you have any questions about SoloStar or diabetes, ask your doctor or pharmacist or contact the local representative
of the Marketing Authorisation Holder shown on the front of this leaflet.

Schematic illustration of the pen
Important information for using SoloStar:

• Always insert a new needle before each use. Use only needles approved for use with SoloStar.
• Do not select a dose and/or press the injection button without a needle inserted
• Always perform the safety test before each injection (see point 3).
• This pen is for personal use only. Do not lend it to anyone else.
• If the injection is given by another person, that person must pay particular attention to avoiding accidental needle injuries and the transmission of infections.
• Do not use SoloStar if it is damaged or if you are unsure of its correct operation.
• Always have a spare SoloStar on hand in case your SoloStar is damaged or lost.

Point 1. Insulin Check

• A.Check the label on the SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a coloured injection button. The colour of the injection button varies depending on the Insuman insulin formulation used. The figures below are for illustrative purposes only.

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• B.Remove the pen cap.
• C.Check the appearance of the insulin.
• If you are using clear insulin (Insuman Rapid), do not use the pen if the insulin is cloudy, coloured, or contains particles.

Point 2. Needle Insertion
Always use a new sterile needle for each injection. This will help prevent contamination and potential
needle blockages.
Before using the needle, carefully read the “Instructions for Use” for the needles.
Note: the needles shown are for illustrative purposes only.

• A.Remove the protective tab from the packaging of a new needle.
• B.Align the needle with the pen and keep it straight while inserting it onto the pen (screw on or push on, depending on the type of needle).

.

• If the needle is not held straight while inserting it, you may damage the rubber seal and cause leaks, or you may break the needle.

Point 3. Perform the safety test
Always perform the safety test before each injection. This ensures the delivery of a correct
dose because:

• it ensures that the pen and needle are working correctly
• it removes air bubbles
• A.Select a dosage of 2 units by rotating the dosage selector.

• B.Remove the outer cap of the needle and keep it to remove the used needle after the injection. Remove the inner cap of the needle and discard it.

267

• C.Hold the pen upright with the needle pointing upwards.
• D.Tap the insulin reservoir with your finger so that any air bubbles rise to the needle.
• E.Press the injection button all the way down. Check that insulin comes out of the needle tip. HoldDiscard

You may need to repeat the safety test several times before insulin comes out.

• If the insulin does not come out, check for air bubbles and repeat the safety test two or more times to remove them.
• If the insulin still does not come out, the needle may be blocked. Change the needle and try again.
• If the insulin still does not come out after changing the needle, the SoloStar may be damaged. Do not use this SoloStar.

Point 4. Dose Selection
The dose can be selected in 1-unit increments, from a minimum of 1 unit to a maximum of 80
units. If a dose greater than 80 units is needed, it must be administered by two or more
injections.

• A.Check that the dosage window shows “0” at the end of the safety test.
• B.Select the required dose (in the example below, the selected dose is 30 units). If a higher dose has been selected, you can rotate the dosage selector in the opposite direction.

• Do not push the injection button while rotating it as insulin will come out.
• You cannot rotate the dosage selector beyond the number of units remaining in the pen. Do not force the dosage selector further. In this case, you can inject what is left in the pen and complete the dose with a new SoloStar or use a new SoloStar for the entire dose.

268

Point 5. Injecting the dose

• A.Use the injection technique as instructed by your doctor, pharmacist or nurse.
• B.Insert the needle into the skin.

• C.Administer the dosage by pressing the injection button all the way down. The number appearing in the dosage window will return to “0” during the injection.

• D.Keep the injection button pressed all the way down. Count slowly to 10 before removing the needle from the
  skin. This ensures that the entire dose of insulin has been injected.

The pen plunger moves with each dose. The plunger reaches the end of the cartridge when
300 total units of insulin have been used.

Point 6. Needle Removal and Disposal
Always remove the needle after each injection and store SoloStar without the needle inserted.
This helps to prevent:

• contamination and/or infection,
• air entering the insulin reservoir and insulin leakage, which can cause inaccurate dosing.
• A.Put the outer cap back on the needle and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never reposition the inner cap of the needle.
• If the injection is given by another person, or if you are giving the injection to another person, you must take particular care when removing and disposing of the needle. Follow the recommended safety measures for needle removal and disposal (ask your doctor, pharmacist or nurse) to reduce the risk of accidental needle injury and the transmission of infectious diseases.
• B.Dispose of the needle safely.
• C.Reposition the cap on the pen, then store the pen until the next injection.

269

Storage Instructions
Refer to the back of this leaflet (insulin) for instructions on how to store SoloStar.
If your SoloStar is stored in the refrigerator, remove it 1-2 hours before injection so that it can
warm up to room temperature. Injecting cold insulin is more painful.
Dispose of your used SoloStar in accordance with local legal requirements.

Maintenance
SoloStar must be protected from dust and dirt.
The exterior of SoloStar can be cleaned with a damp cloth.
Do not wet, wash or lubricate the pen as this could damage it.
Your SoloStar is designed to operate safely and accurately. It must be handled with care.
Situations in which SoloStar could be damaged must be avoided. If you are concerned that SoloStar is
damaged, use a new one.
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F ull prescribing information: information for the user

Insuman Basal 100 IU/ml injectable suspension in a vial

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Basal is and what it is used for
• 2. What you need to know before you use Insuman Basal
• 3. How to use Insuman Basal
• 4. Possible side effects
• 5. How to store Insuman Basal
• 6. Contents of the pack and other information

1. What is Insuman Basal and what is it used for

Insuman Basal contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Basal is an insulin preparation with a gradual onset of action and a long duration of action.
The insulin is present as fine protamine insulin crystals.
Insuman Basal is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Basal

Do not use Insuman Basal
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Basal.
Follow the instructions your doctor has given you strictly regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
271
Skin changes at the injection site:
The injection site must be rotated to prevent skin changes, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Basal). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
ask you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic medicines.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, diabetes control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or carbohydrate intake. It is necessary to inform people close to you about your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Tell your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or localized swelling (edema).

Other medicines and Insuman Basal
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),

272

• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely eliminate the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Basal with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Basal in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.

Driving and using machines
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. 273

Take this into account in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your
doctor for advice on whether it is appropriate for you to drive if:

• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Basal
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of blood sugar level tests (glycemia), the doctor will:

• establish the daily amount of Insuman Basal you need,
• inform you of when you must check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Basal is needed.

Many factors can influence your blood sugar levels. It is advisable that you know these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Basal is injected subcutaneously 45 - 60 minutes before a meal.

Method of administration
Insuman Basal is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Basal into a vein (blood vessel).
The doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Basal in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the vials
Insuman Basal contains 100 IU of insulin per ml. Only syringes for injection suitable for this
concentration (100 IU per ml) must be used. Injection syringes must not contain other
medicines or their residues (such as traces of heparin).
Before drawing up the insulin for the first time, remove the tear-off safety cap
from the vial.
Immediately before each injection, mix the insulin well. To do this, rotate the vial diagonally
between the palms of your hands. Do not shake the vial vigorously because this may damage the insulin and cause foaming. Foam may
interfere with accurate dose measurement.
After mixing, the liquid should appear uniformly milky. It should not be used if the
suspension remains clear or, for example, if small lumps, particles or flakes or similar form
inside or on the wall or bottom of the vial. In these cases, another vial should be used, the contents of which have a uniform appearance.
Always use a new vial if you notice that your blood sugar control has
unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you think
you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Special precautions before injection
Air bubbles must be removed before injection. Make sure that neither alcohol nor other disinfectants
nor other contaminating substances contaminate the insulin. Do not mix the insulin with other medicines, except for the
human insulin formulations listed below.
Insuman Basal can be mixed with all human insulin formulations, EXCEPT those specifically designed
for use in insulin pumps. Also, DO NOT mix with animal insulins or
insulin analogues.
The doctor will tell you if it is necessary to mix human insulins. If it is necessary to inject a mixture, draw the other
insulin into the injection syringe before Insuman Basal. Proceed with the injection immediately after
mixing. Do not mix insulins with different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Basal than you should

• If you have injected too high a dose of Insuman Basal, your blood sugar levels may become too low (hypoglycemia). Check your blood sugar frequently. In general, to prevent hypoglycemia, you should consume more substantial meals and check your blood sugar. For information on treating hypoglycemia, see the box at the end of this leaflet.

If you forget to use Insuman Basal

• If you have forgotten a dose of Insuman Basalor have not injected enough insulin, your blood sugar levels may become too high (hyperglycemia). Check your blood sugar frequently. For information on treating hyperglycemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Basal
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (build-up
of acid in the blood because the body is metabolizing fat instead of sugar). Do not stop Insuman
Basal without consulting a doctor who will tell you what you need to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicine between
Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
275
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)
)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause myocardial infarction or brain damage and can be life-threatening. For further information on the side effects of low or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Changes in the skin at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.
276

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package and on the vial label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Unused vials:
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Basal in direct contact with the
freezer compartment or with cooling packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials:
Once in use, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C, protected from a direct source of heat (e.g. radiator) or from direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Basal contains

• The active substance is human insulin. 1 ml of Insuman Basal contains 100 IU (International Units) of the active substance human insulin.
• The other ingredients are: protamine sulfate, meta-cresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Basal and content of the pack
After mixing, Insuman Basal is a uniformly milky liquid (injectable suspension), without
clumps, flakes or visible particles.
Insuman Basal is supplied in vials containing 5 ml of injectable suspension (equivalent to 500 IU) or
10 ml of injectable suspension (equivalent to 1000 IU). Packs of 1 and 5 vials of 5
ml or 10 ml are available. Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the marketing authorisation
holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40
277

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V .
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop
Industrie Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300
278

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Basal”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, facial redness, loss of appetite,
low blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
Check your blood sugar and the presence of ketones in your urine as soon as possible if you experience any of the symptoms listed above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
279
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognise when your blood sugar levels are dropping too low, so
you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhoea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from illness or fever,
• you are taking or have taken other medicines (see section 2, “Other medicines and Insuman Basal”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show fluctuations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a decrease in brain sugar levels.
• In the brain Examples of symptoms indicating a decrease in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Basal”).

280
In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognising it in time. Therefore, learn to recognise the warning symptoms of hypoglycemia. If necessary, more frequent blood sugar checks may help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognise the warning symptoms of hypoglycemia, avoid all situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. Then consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should have previously discussed these measures with you.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar.
• 4. Talk to your doctor as soon as you notice that you are unable to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues close to you that:
If you are unable to swallow or lose consciousness, action must be taken with an injection of glucose or
glucagon (a medicine that increases blood sugar levels). These injections are also justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
281

Insuman Basal 40 UI/ml injectable suspension in a vial

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Basal is and what it is used for
• 2. What you need to know before you use Insuman Basal
• 3. How to use Insuman Basal
• 4. Possible side effects
• 5. How to store Insuman Basal
• 6. Contents of the pack and other information

1. What is Insuman Basal and what is it used for

Insuman Basal contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Basal is an insulin preparation with a gradual onset of action and a long duration of action.
The insulin is present as fine protamine insulin crystals.
Insuman Basal is used to lower elevated blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Basal

Do not use Insuman Basal
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Basal.
Follow strictly the instructions given to you by your doctor regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
282
Changes in the skin at the injection site:
The injection site must be rotated to prevent changes in the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Basal). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic medicines.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illness and injuries
In the following situations, diabetes control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or carbohydrate intake. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Basal
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression), 283
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progesterone (such as in the birth control pill used for birth control),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• beta-blockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Beta-blockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Basal with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Basal in pregnancy.
If you are breastfeeding, consult your doctor, as changes in the dose of insulin and
diet may be necessary.

Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. 284

Take into account the possibility that this may occur in all situations where you could pose a
risk to yourself and others (such as driving a car or using machinery). Ask your
doctor for advice on whether you should drive if:

• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Basal
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose
Use this medicine following exactly the instructions of your doctor. If you have doubts, consult your doctor or pharmacist.
Based on your lifestyle and the results of blood sugar level tests (glycemia), your doctor will:

• establish the daily amount of Insuman Basal you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Basal is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these factors so that you can act appropriately in case of changes in blood sugar levels and thus avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Frequency of administration
Insuman Basal is injected subcutaneously 45 - 60 minutes before a meal.

Method of administration
Insuman Basal is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Basal into a vein (blood vessel).
Your doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site within the chosen skin area.
Do not use Insuman Basal in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the vials
Insuman Basal contains 40 IU of insulin per ml. Only syringes suitable for injection for this concentration (40 IU per ml) must be used. Injection syringes must not contain other medicines or their residues (such as traces of heparin).
Before drawing up the insulin for the first time, you must remove the tear-off safety cap from the vial.
Immediately before each injection, mix the insulin well. To do this, rotate the vial diagonally between the palms of your hands. Do not shake the vial vigorously as this may damage the insulin and cause foaming. Foam may interfere with the correct measurement of the dose.
After mixing, the liquid should appear uniformly milky. It should not be used if the suspension remains clear or, for example, if small lumps, particles or flakes or similar form inside or on the wall or bottom of the vial. In these cases, another vial should be used whose contents have a uniform appearance.
Always use a new vial if you notice that blood sugar control has unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Particular precautions before injection
Air bubbles must be removed before injection. Make sure that neither alcohol nor other disinfectants or other contaminating substances contaminate the insulin. Do not mix the insulin with other medicines, except for the human insulin formulations listed below.
Insuman Basal can be mixed with all human insulin formulations, EXCEPT those specifically intended for use in insulin pumps. Also, DO NOT mix with animal insulins or insulin analogues.
Your doctor will tell you if it is necessary to mix insulins. If it is necessary to inject a mixture, draw the other insulin into the injection syringe before Insuman Basal. Proceed with the injection immediately after mixing. Do not mix insulins of different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Basal than you should

• If you have injected too high a dose of Insuman Basal, blood sugar levels may become too low (hypoglycemia). Check your blood sugar frequently. In general, to prevent hypoglycemia, you should eat more substantial meals and check your blood sugar. For information on the treatment of hypoglycemia, see the section at the end of this leaflet.

If you forget to use Insuman Basal

• If you have forgotten a dose of Insuman Basalor have not injected enough insulin, blood sugar levels may become too high (hyperglycemia). Check your blood sugar frequently. For information on the treatment of hyperglycemia, see the section at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Basal
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar). Do not stop Insuman Basal without consulting a doctor who will tell you what you need to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicine between Insuman Basal and other insulins.

4. Possible side effects

286
Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulinmay occur, which could be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with a rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Changes in the skin at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances may spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies necessitate an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through
the national reporting system listed in Annex V.
287
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package and on the vial label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Unused vials:
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Basal in direct contact with the
freezer compartment or with cooling packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials:
Once in use, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C, protected from a direct heat source (e.g. radiator) or direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

• The active ingredient is human insulin. 1 ml of Insuman Basal contains 40 IU (International Units) of the active ingredient human insulin.
• The other ingredients are: protamine sulfate, meta-cresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Basal and contents of the pack
After mixing, Insuman Basal is a uniformly milky liquid (injectable suspension), without
clumps, flakes or visible particles.
Insuman Basal is supplied in vials containing 10 ml of suspension (400 IU). Packs of 1 and 5 vials of 10 ml are available.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the Marketing Authorisation
Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40
288

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi România S.R.L.
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical inquiries)
800 536389 (other inquiries)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00
289

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (for example, because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Basal”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, facial flushing, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
Check your blood sugar and the possible presence of ketones in your
urine as soon as possible if any of the symptoms mentioned above occur.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognize when your blood sugar levels are dropping too low, so that you can take appropriate precautions.
290

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains less carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Basal”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of the skin where you inject the insulin (for example from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggressiveness, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (for example the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Basal”).

In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognizing it in time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more
frequent blood sugar checks may be helpful in identifying mild hypoglycemic episodes that might otherwise
go unnoticed. If you are unable to recognize the warning symptoms of hypoglycemia, avoid all those
situations (such as driving a car) that may be risky for you and others due to hypoglycemia. 291

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should have previously discussed these measures with you.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar.
• 4. Talk to your doctor as soon as you realize that you are unable to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues close to you that:
If you are unable to swallow or lose consciousness, intervention with an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are also justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm that a hypoglycemic episode was occurring. 292

Insuman Basal 100 IU/ml injectable suspension in a cartridge

Human insulin

Read this leaflet carefully before you start to use this medicine as it contains important
information for you. Instructions for using the insulin pen are provided with your insulin pen.
Refer to these before using your medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Basal is and what it is used for
• 2. What you need to know before you use Insuman Basal
• 3. How to use Insuman Basal
• 4. Possible side effects
• 5. How to store Insuman Basal
• 6. Contents of the pack and other information

1. What is Insuman Basal and what is it used for

Insuman Basal contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Basal is an insulin preparation with a gradual onset of action and a long duration of action.
The insulin is present as fine protamine insulin crystals.
Insuman Basal is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Basal

Do not use Insuman Basal
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Basal in cartridges is only suitable for subcutaneous injections with a reusable pen (see
also section 3). Talk to your doctor if you need to inject the insulin using a different method.
Consult your doctor, pharmacist or nurse before using Insuman Basal.
Follow the instructions given to you by your doctor strictly regarding the dose, checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
293
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Changes to the skin at the injection site:
The injection site must be rotated to prevent changes to the skin, such as the appearance of nodules
under the skin. The insulin may not work as well as it should if you inject it into an area with
nodules (see section How to use Insuman Basal). If you are currently injecting into an area with
nodules, consult your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust your insulin or other antidiabetic medicines.
Travel
Consult your doctor before starting a trip. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, control of diabetes may require great attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Furthermore, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to inform people close to you about your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or localized swelling (edema).

Other medicines and Insuman Basal
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if this can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes, 294
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progesterone (as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Basal with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Basal in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.
295

Driving and using machines
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take this into account in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Basal
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of blood sugar level tests (glycemia), the doctor:

• will determine the daily amount of Insuman Basal you need,
• will inform you of when you need to check your blood sugar and, if necessary, when to perform urine tests,
• will inform you if a lower or higher dose of Insuman Basal is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these factors so that you can act appropriately in case of changes in blood sugar levels and thus avoid them becoming too high or too low. For further information, see the box at the end of this leaflet.

Frequency of administration
Insuman Basal is injected subcutaneously 45 - 60 minutes before a meal.

Method of administration
Insuman Basal is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Basal into a vein (blood vessel).
The doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site within the chosen skin area.
Do not use Insuman Basal in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the cartridges
Insuman Basal in cartridges is intended only for subcutaneous injections with a reusable pen. Talk to your doctor if you need to inject insulin in another way.
To ensure the administration of the correct dose, Insuman Basal cartridges must be used only with the following pens:

• JuniorStar for the administration of Insuman Basal with dose increments of 0.5 units 296
• ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO for the administration of Insuman Basal with dose increments of 1 unit. It is possible that not all pens are marketed in your country.

The pens must be used as recommended in the information provided by the device manufacturer. For loading the cartridge, inserting the injection needle and administering the insulin injection, carefully follow the manufacturer's instructions for using the pen.
It is recommended to store the cartridge at room temperature for 1 or 2 hours before inserting it into the pen.
Mix the insulin well and check it before inserting it into the pen. Afterwards, the insulin must always be mixed very well, immediately before each injection.
Mixing is best done by gently tilting the cartridge or pen (with the cartridge inserted) back and forth at least 10 times. To facilitate mixing, each cartridge contains three small metal balls.
After mixing, the liquid should appear uniformly milky. It should not be used if the suspension remains clear or, for example, if small lumps, particles or flakes or similar form inside it or on the wall or bottom of the cartridge. In these cases, another cartridge should be used, the contents of which have a uniform appearance.
Always use a new cartridge if you notice that your blood sugar control has unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Particular precautions before injection
Air bubbles must be removed before injection (see the instructions for using the pen).
Make sure that neither alcohol nor other disinfectants or other contaminating substances contaminate the insulin.

• Do not refill or reuse empty cartridges.
• Do not add other insulins to the cartridges.
• Do not mix the insulin with other medicines.

Problems with the pen?
Refer to the manufacturer's instructions for using the pen.
If the insulin pen is damaged or does not work properly (due to mechanical defects) it must be discarded and a new insulin pen must be used.
If you use more Insuman Basal than you should

• If you have injected too high a dose of Insuman Basal, blood sugar levels may become too low (hypoglycemia). Check your blood sugar frequently. In general, to prevent hypoglycemia, you should consume more substantial meals and check your blood sugar. For information on treating hypoglycemia, see the box at the end of this leaflet.

If you forget to use Insuman Basal

• If you have forgotten a dose of Insuman Basalor have not injected enough insulin, blood sugar levels may become too high (hyperglycemia). Check your blood sugar frequently. For information on treating hyperglycemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

297

If you stop treatment with Insuman Basal
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar). Do not stop Insuman Basal without consulting a doctor who will tell you what is necessary to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicine between Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes. 298
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the cartridge label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Unused cartridges
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Basal in direct contact with the
freezer compartment or with cooling packs. Store the cartridge in the outer packaging to
protect the medicine from light.
Cartridges in use
Cartridges in use (in the insulin pen) or kept as “spare”, can be stored for a maximum
of 4 weeks at a temperature not exceeding 25°C away from a direct source of heat (e.g.
radiator) or direct light (direct sunlight or lamp). The cartridge in use must not be stored in
the refrigerator. Do not use the cartridge after this period.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

• The active substance is human insulin. 1 ml of Insuman Basal contains 100 IU (International Units) of the active substance human insulin.
• The other ingredients are: protamine sulfate, meta-cresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Basal and contents of the pack
After mixing, Insuman Basal is a uniformly milky liquid (injectable suspension), without
clumps, flakes or visible particles.
Insuman Basal is supplied in cartridges containing 3 ml of suspension (300 IU). Packs containing
3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available.
Not all pack sizes may be marketed.
299

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicinal product, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00
300

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (for example, because it was not stored correctly),
• the insulin pen is not working properly,
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Basal”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, redness of the face, loss of appetite,
low blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
Check your blood sugar and the presence of ketones in your
urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognize when your blood sugar levels are dropping too low, so that you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Basal”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (for example from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremors, paralysis, sensory disturbances (paresthesia), sensations of tingling and of 302

numbness in the mouth, dizziness, loss of self-control, inability to care for oneself,
convulsions, loss of consciousness.
The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (for example the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken other medicines (see section 2 “Other medicines and Insuman Basal”).

In these cases, a severe hypoglycemia (even with loss of consciousness) can develop without
recognizing it in time. Therefore, learn to recognize the warning symptoms of hypoglycemia. If necessary, more frequent blood sugar checks may help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should discuss these measures with you beforehand.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you realize that you are unable to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, intervention with an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood glucose immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
303

Insuman Basal SoloStar 100 IU/ml injectable suspension in a pre-filled pen

Human insulin

Read this leaflet carefully, including the instructions for use of the Insuman Basal SoloStar pre-filled pen, before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Basal is and what it is used for
• 2. What you need to know before you use Insuman Basal
• 3. How to use Insuman Basal
• 4. Possible side effects
• 5. How to store Insuman Basal
• 6. Contents of the pack and other information

1. What is Insuman Basal and what is it used for

Insuman Basal contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Basal is an insulin preparation with a gradual onset of action and a long duration of action.
The insulin is present as fine crystals of protamine insulin. It is presented in cartridges contained in a disposable pen injector, SoloStar.
Insuman Basal is used to lower high blood sugar levels in patients with diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Basal

Do not use Insuman Basal
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Basal is only suitable for subcutaneous injections (see also section 3). Talk to your doctor if
you need to inject the insulin in a different way.
Consult your doctor, pharmacist or nurse before using Insuman Basal.
Follow the instructions given to you by your doctor strictly regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise), injection technique.
Tell your doctor if you are allergic to this medicine or to animal insulins.
304
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Changes in the skin at the injection site:
The injection site must be rotated to prevent changes in the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject it into an area with
nodules (see section How to use Insuman Basal). If you are currently injecting into an area with
nodules, consult your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic medicines.
Travel
Consult your doctor before starting a trip. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of changing time zones,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, blood sugar control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Basal
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes, 305
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Basal with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding
ask your doctor or pharmacist for advice before using this medicine.
Inform your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Basal in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the dose of insulin and
diet may be necessary.
306

Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take this into account in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Basal
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycaemia), your doctor will:

• establish the daily amount of Insuman Basal you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Basal is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these factors so that you can act appropriately in case of changes in blood sugar levels and therefore avoid them becoming too high or too low. For further information, see the section
at the end of this leaflet.

Frequency of administration
Insuman Basal is injected subcutaneously 45 - 60 minutes before a meal.

Method of administration
Insuman Basal is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Basal into a vein (blood vessel).
SoloStar releases insulin in doses from 1 to 80 units in increments of 1 unit. Each pen contains multiple doses.
The doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site within the chosen skin area.

How to handle SoloStar
SoloStar is a disposable pre-filled pen containing human insulin. Insuman Basal in a pre-filled pen
is only suitable for subcutaneous injections. Talk to your doctor if you need to inject insulin in a different way.
307

you must use the pen as described in these Instructions for Use.
A new injection needle must be inserted before each use. Use only needles approved for use with
SoloStar.
A safety test must be performed before each injection.
Mix the insulin well and check it before using it for the first time. Afterwards, the insulin must always be mixed very well, immediately before each injection.
Mixing is best done by gently tilting the pen back and forth at least 10 times. To facilitate mixing, each cartridge contains three small metal balls.
After mixing, the liquid should appear uniformly milky. It should not be used if the suspension remains clear or, for example, if small lumps, particles or flakes or similar form inside or on the wall or bottom of the cartridge in the pen. In these cases, another pen should be used whose contents have a uniform appearance.
Always use a new pen if you notice that your blood sugar control has unexpectedly worsened. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.
To prevent possible transmission of disease, each pen must be used by only one patient.

Special precautions before the injection
Make sure that neither alcohol nor other disinfectants nor other contaminating substances contaminate the insulin.
Do not mix the insulin with other medicines. Insuman Basal SoloStar pre-filled pen has not been studied
for the addition of other insulins into the cartridge.
Empty pens should never be reused and must be disposed of properly.
Do not use SoloStar if it is damaged or does not work properly. It must be disposed of and a new SoloStar must be used.

If you use more Insuman Basal than you should

• If you have injected too high a dose of Insuman Basal, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the section at the end of this leaflet.

If you forget to use Insuman Basal

• If you have forgotten a dose of Insuman Basalor have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the section at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Basal
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman Basal without consulting a doctor who will tell you what is necessary to do.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or nurse.
308

Swapping insulins
You should always check the insulin label before each injection to avoid swapping between Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the section at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which could be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating.

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site, or inflammation in

309
the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.

• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the pen label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Pens not in use
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place the prefilled pen in direct contact with
the freezer compartment or with cooling packs. Store the prefilled pen in the outer packaging
to protect the medicine from light.
Pens in use
Prefilled pens in use or kept “in reserve” may be stored for a maximum of 4 weeks at
a temperature not exceeding 25°C, protected from a source of direct heat (e.g. radiator) or from
direct light (direct sunlight or lamp). The pen in use must not be stored in a refrigerator. Do not use the
pen after this period.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to eliminate
medicines that you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

• The active substance is human insulin. 1 ml of Insuman Basal contains 100 IU (International Units) of the active substance human insulin.
• The other ingredients are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Basal and contents of the pack
After mixing, Insuman Basal is a uniformly milky liquid (injectable suspension), without
clumps, flakes or visible particles.
Insuman Basal SoloStar is supplied in pre-filled pens, containing 3 ml of suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are
available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
310
Germany.
For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop
Industrie Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600
311

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
SanofiOy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected enough
insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• the insulin pen is not working correctly,
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Basal”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
low blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine. Abdominal
pain, deep and rapid breathing, drowsiness or even loss of consciousness may indicate a
serious condition (ketoacidosis) resulting from insulin deficiency.
312

What should you do in case of hyperglycemia?
Check your blood sugar and the possible presence of ketones in your urine as soon as possible
if you experience any of the symptoms listed above.Severe hyperglycemia or ketoacidosis must
always be treated by a doctor, generally in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes can
cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognize when your blood sugar levels are dropping too low, so you can take
appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injuries, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Basal”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), sensations of tingling and numbness in the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be less
noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Basal”). 313

In these cases, a severe hypoglycemia (even with loss of consciousness) can develop without being
recognized for a long time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more
frequent blood sugar checks may help identify mild hypoglycemic episodes that might otherwise
go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid all those
situations (such as driving a car) that may be risky for you and others due to hypoglycemia.

What should you do in case of hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. Then consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should have discussed these measures with you previously.
• 3. If another hypoglycemia occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it occurs again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, intervention with a glucose or glucagon injection is necessary
(a medicine that increases blood sugar levels). These injections are also justified if you are not
sure whether a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm that a hypoglycemic episode was
occurring.
314

Insuman Basal SoloStarinjectable suspension in a pre-filled pen. Instructions for Use.
SoloStar is a pre-filled pen for injecting insulin. Your doctor has decided that SoloStar is suitable for you
based on your ability to use SoloStar. Talk to your doctor, pharmacist or nurse about the correct
injection technique before using SoloStar.
Read these instructions carefully and completely before using your SoloStar. If you are unable to
use SoloStar or follow all the instructions completely on your own, you must only use SoloStar if you can
get help from a person who can follow all the instructions completely. Hold the pen horizontally, with the needle to the left and the dose selector to the right, as shown in the figures below.

Follow these instructions completely each time you use SoloStar to ensure you take an accurate
dose. If you do not follow these instructions completely, you may take too much or too little insulin, which
can change your blood glucose levels.
Doses from 1 to 80 units can be selected in 1-unit increments. Each pen contains multiple doses.
Keep this instruction leaflet for future reference.
If you have any questions about SoloStar or diabetes, ask your doctor or pharmacist or contact the
local representative of the Marketing Authorisation Holder shown on the front of
this leaflet.

Schematic illustration of the pen
Important information for using SoloStar:

• Always insert a new needle before each use. Use only needles approved for use with SoloStar.
• Do not select a dose and/or press the injection button without a needle inserted
• Always perform the safety test before each injection (see point 3).
• This pen is for personal use only. Do not lend it to anyone else.
• If the injection is given by another person, this person must pay particular attention to avoiding accidental needle injuries and the transmission of infections.
• Never use SoloStar if it is damaged or if you are unsure of its correct operation.
• Always have a spare SoloStar on hand in case your SoloStar is damaged or lost.

Point 1. Insulin Check

• A.Check the label on the SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colored injection button. The color of the injection button varies depending on the Insuman insulin formulation used. The figures below are for illustrative purposes only.

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• B.Remove the pen cap.
• C.Check the appearance of the insulin.
• If you are using an insulin suspension (Insuman Basal or Insuman mixtures), tilt the pen back and forth at least 10 times to resuspend the insulin. The pen should be tilted gently to avoid foam formation in the cartridge.

After mixing, check the appearance of your insulin. Insulin suspensions should
appear uniformly cloudy.

Point 2. Needle Insertion
Always use a new sterile needle for each injection. This will help prevent contamination and potential
needle blockage.
Before using the needle, carefully read the “Instructions for Use” for the needles.
Note: the needles shown are for illustrative purposes only.

• A.Remove the protective tab from the packaging of a new needle.
• B.Align the needle with the pen and keep it straight while inserting it onto the pen (screw on or push on, depending on the type of needle).

.

• If the needle is not held straight while being inserted, it may damage the rubber seal and cause leaks, or it may break the needle.

Point 3. Perform the Safety Test
Always perform the safety test before each injection. This ensures the delivery of a correct
dose because:

• ensures that the pen and needle are functioning correctly
• removes air bubbles

316

• A.Select a dosage of 2 units by rotating the dosage selector.

• B.Remove the outer cap from the needle and keep it to remove the used needle after the injection. Remove the inner cap of the needle and discard it.

• C.Hold the pen in a vertical position with the needle pointing upwards.
• D.Tap the insulin reservoir with your finger so that any air bubbles rise to the needle.
• E.Press the injection button all the way down. Check that insulin comes out of the needle tip. Keep Discard

You may need to repeat the safety test several times before insulin comes out.

• If the insulin does not come out, check for air bubbles and repeat the safety test two or more times to remove them.
• If the insulin still does not come out, the needle may be blocked. Change the needle and try again.
• If the insulin does not come out after changing the needle, the SoloStar may be damaged. Do not use this SoloStar.

Point 4. Dose Selection
The dose can be selected in 1-unit increments, from a minimum of 1 unit to a maximum of 80
units. If a dose greater than 80 units is needed, it must be administered by two or more
injections.

• A.Check that the dosage window indicates “0” at the end of the safety test.
• B.Select the required dose (in the example below, the selected dose is 30 units). If a higher dose has been selected, you can rotate the dosage selector in the opposite direction.

317

• Do not push the injection button while rotating as insulin will come out.
• You cannot rotate the dosage selector beyond the number of units remaining in the pen. Do not force the dosage selector further. In this case, you can inject what remains in the pen and complete the dose with a new SoloStar or use a new SoloStar for the entire dose.

Point 5. Dose Injection

• A.Use the injection technique as instructed by your doctor, pharmacist or nurse.
• B.Insert the needle into the skin.

• C.Administer the dosage by pressing the injection button all the way down. The number appearing in the dosage window will return to “0” during the injection.

• D.Keep the injection button pressed all the way down. Count slowly to 10 before removing the needle from the
  skin. This ensures that the entire dose of insulin has been injected.

The pen plunger moves with each dose. The plunger reaches the end of the cartridge when
300 total units of insulin have been used.

Point 6. Needle Removal and Disposal
Always remove the needle after each injection and store SoloStar without the needle inserted.
This helps prevent:

• contamination and/or infection,
• air entering the insulin reservoir and insulin leakage, which can cause inaccurate dosing.
• A.Replace the outer cap on the needle and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never reposition the inner cap of the needle.

318

• If the injection is given by another person, or if you are giving the injection to another person, you must take particular care when removing and disposing of the needle. Follow the recommended safety measures for needle removal and disposal (ask your doctor, pharmacist or nurse) to reduce the risk of accidental needle injury and the transmission of infectious diseases.
• B.Dispose of the needle safely.
• C.Always replace the cap on the pen, then store the pen until the next injection.

Storage Instructions
Refer to the back of this leaflet (insulin) for instructions on how to store SoloStar.
If your SoloStar is stored in the refrigerator, remove it 1-2 hours before injection so that it can
warm to room temperature. Injecting cold insulin is more painful
Dispose of your used SoloStar in accordance with local legal requirements.

Maintenance
SoloStar must be protected from dust and dirt.
The exterior of SoloStar can be cleaned with a damp cloth.
Do not wet, wash or lubricate the pen as this could damage it.
Your SoloStar is designed to operate safely and accurately. It must be handled with care.
Situations in which SoloStar could be damaged must be avoided. If you are concerned that SoloStar is
damaged, use a new one.
319

Insuman Comb 15 100 IU/ml injectable suspension in a vial

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 15 is and what it is used for
• 2. What you need to know before you use Insuman Comb 15
• 3. How to use Insuman Comb 15
• 4. Possible side effects
• 5. How to store Insuman Comb 15
• 6. Contents of the pack and other information

1. What is Insuman Comb 15 and what is it used for

Insuman Comb 15 contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 15 is an insulin preparation with a gradual onset of action and a long duration of action.
Insuman Comb 15 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 15

Do not use Insuman Comb 15
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Comb 15.
Follow the instructions given to you by your doctor carefully regarding the dose, checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special groups of patients
If you have problems with your liver or kidneys, or if you are elderly, consult your doctor because you may need a lower
dose.
320
Changes in the skin at the injection site:
The injection site must be rotated to prevent changes in the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Comb 15). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Consult your doctor before starting a trip. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illness and injuries
In the following situations, blood sugar control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Comb 15
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, an optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping the use of another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin-converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),
• disopyramide (used to treat certain heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood), 321
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progesterone (as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Comb 15 with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Comb 15 in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.

Driving and using machines
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels), 322
• problems with your vision. Take into account the possibility that this may occur in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether it is appropriate for you to drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Comb 15
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 15

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycaemia), your doctor will:

• establish the daily amount of Insuman Comb 15 you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Comb 15 is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Comb 15 is injected subcutaneously 30 – 45 minutes before a meal.

Method of administration
Insuman Comb 15 is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Comb 15 into a vein (blood vessel).
Your doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Comb 15 in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the vials
Insuman Comb 15 contains 100 IU of insulin per ml. Only syringes for injection suitable for this
concentration (100 IU per ml) must be used. The injection syringes must not contain other
medicines or their residues (such as traces of heparin).
Before drawing insulin for the first time, you must remove the tear-off safety cap
from the vial.
Immediately before each injection, mix the insulin well. To do this, rotate the vial diagonally between the palms of your hands. Do not shake the
vial vigorously as this may damage the insulin and cause foaming. Foam may
interfere with correct dose measurement.
After mixing, the liquid should appear uniformly cloudy. It must not be used if the
suspension remains clear or, for example, if small clumps, particles or flakes or similar form
inside or on the wall or bottom of the vial. In these cases, another vial with
uniform content must be used.
Always use a new vial if you notice that your blood sugar control has
unexpectedly deteriorated. This is because the insulin may have lost some of its effectiveness. If you think
you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Special precautions before injection
Air bubbles must be removed before injection. Make sure that neither alcohol nor other disinfectants
nor other contaminants contaminate the insulin. Do not mix the insulin with other medicines, except for the
human insulin formulations listed below.
Insuman Comb 15 can be mixed with all human insulin formulations, EXCEPT those
specifically intended for use in insulin pumps. Also, do NOT mix with animal insulins or insulin analogues.
Your doctor will tell you if you need to mix insulins. If you need to inject a mixture, draw the other
insulin into the injection syringe before Insuman Comb 15. Proceed with the injection immediately after
mixing. Do not mix insulins of different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 15 than you should

• -If you have injected too high a dose of Insuman Comb 15, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the box at the end of this leaflet.

If you forget to use Insuman Comb 15

• -If you have forgotten a dose of Insuman Comb 15or have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Comb 15
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up
of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman
Comb 15 without consulting a doctor who will tell you what you need to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You must always check the insulin label before each injection to avoid exchanging medicines between
Insuman Comb 15 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
324
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulinmay occur, which could be life-threatening. Such reactions to insulin or excipients can cause widespread skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through
the national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.
325

5. How to store Insuman Comb 15

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the vial label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Unused vials:
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Comb 15 in direct contact with the
freezer compartment or with refrigerant packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials:
Once opened, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C, protected from a direct heat source (e.g. radiator) or direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Comb 15 contains

• The active ingredient is human insulin. 1 ml of Insuman Comb 15 contains 100 IU (International Units) of the active ingredient human insulin. 15% of the insulin is dissolved in water; the remaining 85% is present as fine crystals of protamine insulin.
• The other components are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Comb 15”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Comb 15 and contents of the pack
After mixing, Insuman Comb 15 is a uniformly milky liquid (injectable suspension),
without clumps, flakes or visible particles.
Insuman Comb 15 is supplied in vials containing 5 ml of suspension (500 IU). Packs of 1 and 5 vials of 5 ml are available.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the marketing authorisation
holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)
326

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V .
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525
327

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia), you may not have injected
enough insulin.
What causes hyperglycemia?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (for example, because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Comb 15”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do in case of hyperglycemia?
Check your blood sugar and the possible presence of ketones in the
urine as soon as possible if any of the symptoms reported above occur.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, generally in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognize when your blood sugar levels are dropping too low, so you
can take appropriate precautions.

What causes hypoglycemia?
Examples include:

• you injected too much insulin, 328
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Comb 15”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (for example from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), sensations of tingling and numbness in the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (for example the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Comb 15”).

In these cases, a severe hypoglycemia (even with loss of consciousness) can develop without
recognizing it in time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more frequent blood sugar checks can help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid any situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do in case of hypoglycemia?
329

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a long-term release of sugar into the blood (such as bread or pasta). Your doctor or nurse should have previously discussed these measures with you.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it occurs again.

Inform your relatives, friends and colleagues close to you that:
If you are unable to swallow or lose consciousness, an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure whether a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
330

Insuman Comb 15 100 IU/ml injectable suspension in a cartridge

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you. Instructions for using the insulin pen are provided with your insulin pen.
Refer to these before using your medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 15 is and what it is used for
• 2. What you need to know before you use Insuman Comb 15
• 3. How to use Insuman Comb 15
• 4. Possible side effects
• 5. How to store Insuman Comb 15
• 6. Contents of the pack and other information

1. What is Insuman Comb 15 and what is it used for

Insuman Comb 15 contains the active substance human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 15 is an insulin preparation with a gradual onset of action and a long duration of action.
Insuman Comb 15 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 15

Do not use Insuman Comb 15
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Comb 15 in cartridges is only suitable for subcutaneous injections with a reusable pen
(see also section 3). Talk to your doctor if you need to inject the insulin in a different way.
Contact your doctor, pharmacist or nurse before using Insuman Comb 15.
Follow the instructions given to you by your doctor strictly regarding the dose, checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
331
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Changes of the skin at the injection site:
The injection site must be rotated to prevent changes of the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Comb 15). If you are currently injecting into an area with
nodules, contact your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic medicines.
Travel
Before starting a trip consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, control of diabetes may require a lot of attention:

• If you are ill or have serious injuries there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus) do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines and Insuman Comb 15
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping the use of another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes, 332
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progesterone (as in the birth control pill used for birth control),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Comb 15 with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Inform your doctor if you are planning a pregnancy or are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Comb 15 in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.
333

Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take this into account in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Comb 15
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 15

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycemia), the doctor:

• will establish the daily amount of Insuman Comb 15 you need,
• will inform you of when you must check your blood sugar and, if necessary, when to perform urine tests,
• will inform you if a lower or higher dose of Insuman Comb 15 is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Comb 15 is injected subcutaneously 30 – 45 minutes before a meal.

Method of administration
Insuman Comb 15 is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Comb 15 into a vein (blood vessel).
The doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Comb 15 in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the cartridges
Insuman Comb 15 in cartridges is only suitable for subcutaneous injections with a reusable pen. Talk
to your doctor if you need to inject insulin using another method. To ensure the correct dose is administered, the cartridges of Insuman Comb 15 must be used only with the following pens:

• JuniorStar for the administration of Insuman Comb 15 with dose increments of 0.5 units 334
• ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO for the administration of Insuman Comb 15 with dose increments of 1 unit. It is possible that not all pens are marketed in your country.

The pens must be used as recommended in the information provided by the manufacturer of the
device. To load the cartridge, insert the injection needle and administer the insulin injection, carefully follow the manufacturer's instructions for using the pen.
It is recommended to store the cartridge at room temperature for 1 or 2 hours before inserting it into the pen.
Mix the insulin well and check it before inserting it into the pen. Afterwards, the insulin must always be
mixed very well immediately before each injection.
Mixing is best done by gently tilting the cartridge or pen (with the
cartridge inserted) back and forth at least 10 times. To facilitate mixing, each cartridge contains three small metal balls.
After mixing, the liquid should appear uniformly milky. It should not be used if the
suspension remains clear or, for example, if small clumps, particles or flakes or similar form
inside or on the wall or bottom of the cartridge. In these cases, another cartridge should be used whose
contents have a uniform appearance.
Always use a new cartridge if you notice that your blood sugar control is
unexpectedly worsening. This is because the insulin may have lost some of its effectiveness. If you think
you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Special precautions before injection
Air bubbles must be removed before injection (see the instructions for using the pen).
Make sure that neither alcohol nor other disinfectants or other contaminating substances contaminate the insulin.

• Do not refill or reuse empty cartridges.
• Do not add other insulins to the cartridges.
• Do not mix the insulin with other medicines.

Problems with the pen?
Refer to the manufacturer's instructions for using the pen.
If the insulin pen is damaged or does not work properly (due to mechanical
defects) it must be discarded and a new insulin pen must be used.
If you use more Insuman Comb 15 than you should

• -If you have injected too high a dose of Insuman Comb 15, your blood sugar levels may become too low (hypoglycemia). Check your blood sugar frequently. In general, to prevent hypoglycemia, you should consume more substantial meals and check your blood sugar. For information on treating hypoglycemia, see the box at the end of this leaflet.

If you forget to use Insuman Comb 15

• If you have forgotten a dose of Insuman Comb 15or have not injected enough insulin, your blood sugar levels may become too high (hyperglycemia). Check your blood sugar frequently. For information on treating hyperglycemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

335

If you stop treatment with Insuman Comb 15
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (build-up of
acid in the blood because the body is metabolizing fat instead of sugar). Do not stop Insuman
Comb 15 without consulting a doctor who will tell you what is necessary to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicines between
Insuman Comb 15 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most common side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you suffer from proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: how often this occurs is not known). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes. 336
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site, or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system indicated in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Comb 15

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the cartridge label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Unused cartridges
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Comb 15 in direct contact with the
freezer compartment or with cooling packs. Store the cartridge in the outer packaging to
protect the medicine from light.
Cartridges in use
Cartridges in use (in the insulin pen) or kept as “spare”, can be stored for a maximum
of 4 weeks at a temperature not exceeding 25°C, protected from a direct heat source (e.g.
radiator) or direct light (direct sunlight or lamp). The cartridge in use must not be stored in
the refrigerator. Do not use the cartridge after this period.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of the
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 15 contains

• The active substance is human insulin. 1 ml of Insuman Comb 15 contains 100 IU (International Units) of the active substance human insulin. 15% of the insulin is dissolved in water; the remaining 85% is present as fine crystals of protamine insulin.
• The other components are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Comb 15”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Comb 15 and contents of the pack
After mixing, Insuman Comb 15 is a uniformly milky liquid (injectable suspension),
without clumps, flakes or visible particles.
337
Insuman Comb 15 is supplied in cartridges containing 3 ml of suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400
338

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia), you may not have injected
enough insulin.
339

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (for example, because it was not stored correctly),
• the insulin pen is not working properly,
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Comb 15”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
low blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
Check your blood sugar and the presence of ketones in your urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. You should generally be able to
recognize when your blood sugar levels are dropping too low, so you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains less carbohydrates than usual (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Comb 15”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject insulin (for example from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

340

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (for example the day before) or if hypoglycemia appears slowly,
• blood sugar levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2 “Other medicines and Insuman Comb 15”).

In these cases, a severe hypoglycemia (even with loss of consciousness) can develop without
recognizing it in time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more
frequent blood sugar checks may be helpful in identifying mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should discuss these measures with you beforehand.
• 3. If you experience another hypoglycemia, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues close to you that:
If you are unable to swallow or lose consciousness, intervention with an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
341

Insuman Comb 15 SoloStar 100 UI/ml injectable suspension in a pre-filled pen

Human insulin

Read this leaflet carefully, including the instructions for use of the Insuman Comb 15 SoloStar pre-filled pen, before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 15 is and what it is used for
• 2. What you need to know before you use Insuman Comb 15
• 3. How to use Insuman Comb 15
• 4. Possible side effects
• 5. How to store Insuman Comb 15
• 6. Contents of the pack and other information

1. What is Insuman Comb 15 and what it is used for

Insuman Comb 15 contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 15 is an insulin preparation with a gradual onset of action and a long duration of action.
It is presented in cartridges contained in a disposable SoloStar pen injector.
Insuman Comb 15 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 15

Do not use Insuman Comb 15
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Comb 15 pre-filled pen is only suitable for subcutaneous injections (see also section
3). Talk to your doctor if you need to inject insulin in a different way.
Contact your doctor, pharmacist or nurse before using Insuman Comb 15.
Follow the instructions given to you by your doctor very carefully regarding the dose, checks to be performed (blood
and urine), diet and physical activity (work and exercise), injection technique.
Tell your doctor if you are allergic to this medicine or to animal insulins.
342
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Changes to the skin at the injection site:
The injection site must be rotated to prevent changes to the skin, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject it into an area with
nodules (see section How to use Insuman Comb 15). If you are currently injecting into an area with
nodules, contact your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the change in time zone,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, blood sugar control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a history of stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines andInsuman Comb 15
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, an optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when you start or
stop using another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:
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• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as in the birth control pill used for birth control),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely eliminate the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Comb 15 with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect or are planning a pregnancy, or if you are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before using this medicine .
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Comb 15 in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the dose of insulin and
diet may be necessary.
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Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take into account the possibility that this may occur in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Comb 15
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 15

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, ask your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycaemia), your doctor will:

• establish the daily amount of Insuman Comb 15 you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Comb 15 is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these factors so that you can act appropriately in case of changes in blood sugar levels and therefore avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Frequency of administration
Insuman Comb 15 is injected subcutaneously 30 – 45 minutes before a meal.

Method of administration
Insuman Comb 15 is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Comb 15 into a vein (blood vessel).
SoloStar delivers insulin in doses from 1 to 80 units in 1-unit increments. Each pen contains multiple doses.
Your doctor will tell you in which area of the skin you should inject the insulin. For each injection, change the injection site within the chosen skin area.

How to handle SoloStar
SoloStar is a disposable pre-filled pen containing human insulin. Insuman Comb 15 in a pre-filled pen is only suitable for subcutaneous injections. Talk to your doctor if you need to inject insulin in another way.
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you must use the pen as described in these Instructions for Use.
A new injection needle must be inserted before each use. Use only needles approved for use with SoloStar.
A safety test must be performed before each injection.
Mix the insulin well and check it before using it for the first time. Afterwards, the insulin must always be mixed very well, immediately before each injection.
Mixing is best done by gently tilting the pen back and forth at least 10 times. To facilitate mixing, each cartridge contains three small metal balls.
After mixing, the liquid should appear uniformly milky. It should not be used if the suspension remains clear or, for example, if small lumps, particles or flakes or similar form inside or on the wall or bottom of the cartridge in the pen. In these cases, another pen should be used whose contents have a uniform appearance.
Always use a new pen if you notice that your blood sugar control has unexpectedly worsened. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.
To prevent possible transmission of disease, each pen must be used by only one patient.

Special precautions before the injection
Make sure that neither alcohol nor other disinfectants or other contaminating substances contaminate the insulin.
Do not mix insulin with other medicines. Insuman Comb 15 pre-filled pen, SoloStar has not been studied for the addition of other insulins into the cartridge.
Empty pens should never be reused and must be disposed of properly.
Do not use SoloStar if it is damaged or does not work properly. It must be disposed of and a new SoloStar must be used.

If you use more Insuman Comb 15 than you should

• -If you have injected too high a dose of Insuman Comb 15, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the section at the end of this leaflet.

If you forget to use Insuman Comb 15

• If you have forgotten a dose of Insuman Comb 15or have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the section at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Comb 15
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman Comb 15 without consulting a doctor who will tell you what you need to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.
346

Swapping insulins
You should always check the insulin label before each injection to avoid swapping between Insuman Comb 15 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the section at the end of this leaflet.
• Severe, widespread allergic reactions to insulinmay occur, which could be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin may lead to temporary fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash) Side effects reported with unknown frequencySodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily impair vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject it into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site, or inflammation at the injection site). These disturbances may spread around the injection site. Most minor reactions to insulin resolve within a few days or weeks.
• Anti-insulin antibodies

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Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act
against insulin). Only rarely does the presence of such antibodies require an adjustment of the dose
of insulin.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Comb 15

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the pen label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Pens not in use
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place the prefilled pen in direct contact with
the freezer compartment or with cooling packs. Store the prefilled pen in the outer packaging
to protect the medicine from light.
Pens in use
Prefilled pens in use or kept as “reserve” can be stored for a maximum of 4 weeks at
a temperature not exceeding 25°C, protected from a direct heat source (e.g. radiator) or from
direct light (direct sunlight or lamp). The pen in use must not be stored in a refrigerator. Do not use the
pen after this period.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Comb 15 contains

• The active ingredient is human insulin. 1 ml of Insuman Comb 15 contains 100 IU (International Units) of the active ingredient human insulin. 15% of the insulin is dissolved in water; the remaining 85% is present as fine crystals of protamine insulin.
• The other components are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Comb 15”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Comb 15 and contents of the pack
After mixing, Insuman Comb 15 is a uniformly milky liquid (injectable suspension),
without clumps, flakes or visible particles.
Insuman Comb 15 SoloStar is supplied in pre-filled pens, containing 3 ml of suspension (300 IU).
Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be
marketed.

Marketing Authorisation Holder and Manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
348
For further information on this medicine, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600
349

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (domande di tipo tecnico)
800 536389 (altre domande)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you have not injected insulin or have administered an insufficient amount, or when the insulin becomes less effective (e.g. because it has not been stored correctly),
• the insulin pen is not working correctly,
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 15”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
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Check your blood sugar and the presence of ketones in your urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognize when your blood sugar levels are dropping too low, so you
can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you have injected too much insulin,
• you have skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from illness or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 15”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), tingling and numbness of the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly, 351
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 15”).

In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognizing it in time. Therefore, learn to recognize the warning signs of hypoglycemia. If necessary, more frequent blood sugar checks may be helpful in identifying mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning signs of hypoglycemia, avoid all situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a long-term release of sugar into the blood (such as bread or pasta). Your doctor or nurse should discuss these measures with you beforehand.
• 3. If another hypoglycemia occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it occurs again.

Inform your relatives, friends and colleagues close to you that:
If you are unable to swallow or lose consciousness, action must be taken with an injection of glucose or
glucagon (a medicine that increases blood sugar levels). These injections are justified
even if you are not sure that a hypoglycemic event has occurred.
Blood sugar should be checked immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
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Insuman Comb 15 SoloStarinjectable suspension in a pre-filled pen. Instructions for Use.
SoloStar is a pre-filled pen for injecting insulin. Your doctor has decided that SoloStar is suitable for you
based on your ability to use SoloStar. Talk to your doctor, pharmacist or nurse about the correct
injection technique before using SoloStar. Read these instructions carefully and completely before using your SoloStar. If you are unable
to use SoloStar or to follow all the instructions completely on your own, you must use SoloStar only if you can
get help from a person who can follow all the instructions completely. Hold the pen horizontally, with the needle to the left and the dose selector to the right, as shown in the figures below.

Follow these instructions completely each time you use SoloStar to ensure you take an accurate
dose. If you do not follow these instructions completely, you may take too much or too little insulin, which
can change your blood glucose levels.
Doses from 1 to 80 units can be selected in 1-unit increments. Each pen contains multiple doses.
Keep this leaflet for future reference.
If you have any questions about SoloStar or diabetes, ask your doctor or pharmacist or contact the local representative
of the Marketing Authorisation Holder shown
on the front of this leaflet.

Schematic illustration of the pen
Important information for using SoloStar:

• Always insert a new needle before each use. Use only needles approved for use with SoloStar.
• Do not select a dose and/or press the injection button without a needle inserted
• Always perform the safety test before each injection (see point 3).
• This pen is for personal use only. Do not lend it to anyone else.
• If the injection is given by another person, that person must take particular care to avoid accidental needle injuries and the transmission of infections.
• Do not use SoloStar if it is damaged or if you are unsure of its correct operation.
• Always have a spare SoloStar available in case your SoloStar is damaged or lost.

Point 1. Insulin Check

• A.Check the label on the SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colored injection button. The color of the injection button varies depending on the Insuman insulin formulation used. The figures below are for illustrative purposes only.
• B.Remove the pen cap. 353

• C.Check the appearance of the insulin.
• If you are using an insulin suspension (Insuman Basal or Insuman mixtures), tilt the pen back and forth at least 10 times to resuspend the insulin. The pen should be tilted gently to avoid foam formation in the cartridge.

After mixing, check the appearance of your insulin. Insulin suspensions should
appear uniformly cloudy.

Point 2. Needle Insertion
Always use a new sterile needle for each injection. This will help prevent contamination and potential
needle blockages.
Before using the needle, carefully read the “Instructions for Use” for the needles.
Note: the needles shown are for illustrative purposes only.

• A.Remove the protective tab from the packaging of a new needle.
• B.Align the needle with the pen and keep it straight while inserting it onto the pen (screw on or press on, depending on the type of needle).

.

• If the needle is not held straight while inserting it, the rubber seal may be damaged and cause leaks, or the needle may break.

Point 3. Perform the safety test
Always perform the safety test before each injection. This ensures the delivery of a correct
dose because:

• ensures that the pen and needle are working correctly
• removes air bubbles

354

• A.Select a dosage of 2 units by rotating the dosage selector.

• B.Remove the outer cap of the needle and save it to remove the used needle after the injection. Remove the inner cap of the needle and discard it.

• C.Hold the pen in a vertical position with the needle pointing upwards.
• D.Tap the insulin reservoir with your finger so that any air bubbles rise to the needle.
• E.Press the injection button all the way down. Check that insulin comes out of the needle tip. HoldDiscard

You may need to repeat the safety test several times before insulin comes out.

• If the insulin does not come out, check for air bubbles and repeat the safety test two or more times to remove them.
• If the insulin still does not come out, the needle may be blocked. Change the needle and try again.
• If the insulin still does not come out after changing the needle, the SoloStar may be damaged. Do not use this SoloStar.

Point 4. Dose Selection
The dose can be selected in 1-unit increments, from a minimum of 1 unit up to a maximum of 80
units. If a dose greater than 80 units is required, it must be administered by two or more
injections.

• A.Check that the dosage window shows “0” at the end of the safety test.
• B.Select the required dose (in the example below, the selected dose is 30 units). If a higher dose has been selected, you can rotate the dosage selector in the opposite direction.

355

• Do not push the injection button while rotating it as insulin will come out.
• You cannot rotate the dosage selector beyond the number of units remaining in the pen. Do not force the dosage selector further. In this case, you can inject what remains in the pen and complete the dose with a new SoloStar or use a new SoloStar for the entire dose.

Point 5. Dose Injection

• A.Use the injection technique as instructed by your doctor, pharmacist or nurse.
• B.Insert the needle into the skin.

• C.Administer the dosage by pressing the injection button all the way down. The number that appears in the dosage window will return to “0” during the injection.

• D.Keep the injection button pressed all the way down. Count slowly to 10 before removing the needle from the
  skin. This ensures that the entire dose of insulin has been injected.

The pen plunger moves with each dose. The plunger reaches the end of the cartridge when
300 total units of insulin have been used.

Point 6. Needle Removal and Disposal
Always remove the needle after each injection and store the SoloStar without the needle inserted.
This helps prevent:

• contamination and/or infection,
• air entering the insulin reservoir and insulin leakage, which can cause inaccurate dosing.
• A.Replace the outer cap on the needle and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner cap of the needle.
• If the injection is given by another person, or if you are giving the injection to another person, you must take particular care when removing and disposing of the needle. Follow the 356

recommended safety measures for needle removal and disposal (ask your doctor, pharmacist or nurse) to reduce the risk of accidental needle injury and transmission of infectious diseases.

• B.Dispose of the needle safely.
• C.Always replace the cap on the pen, then store the pen until the next injection.

Storage Instructions
Refer to the back of this sheet (insulin) for instructions on how to store SoloStar.
If your SoloStar is stored in the refrigerator, remove it 1-2 hours before injection so that it can
warm up to room temperature. Injecting cold insulin is more painful
Dispose of your used SoloStar in accordance with local legal requirements.

Maintenance
SoloStar must be protected from dust and dirt.
The outside of SoloStar can be cleaned with a damp cloth.
Do not wet, wash or lubricate the pen as this may damage it.
Your SoloStar is designed to operate safely and accurately. It must be handled with care.
Situations in which SoloStar could be damaged must be avoided. If you are concerned that SoloStar is
damaged, use a new one.
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Insuman Comb 25 100 IU/ml injectable suspension in a vial

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 25 is and what it is used for
• 2. What you need to know before you use Insuman Comb 25
• 3. How to use Insuman Comb 25
• 4. Possible side effects
• 5. How to store Insuman Comb 25
• 6. Contents of the pack and other information

1. What is Insuman Comb 25 and what is it used for

Insuman Comb 25 contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 25 is an insulin preparation with a gradual onset of action and a long duration of action.
Insuman Comb 25 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 25

Do not use Insuman Comb 25
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine (listed in
section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Comb 25.
Follow the instructions given to you by your doctor strictly regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor as you may need a lower
dose.
Skin changes at the injection site:
358
The injection site must be rotated to prevent skin changes, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Comb 25). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Consult your doctor before starting a trip. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illness and injuries
In the following situations, diabetes control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a history of stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or
localized swelling (edema).

Other medicines andInsuman Comb 25
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping the use of another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase (MAO) inhibitors (used to treat depression), 359
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• beta-blockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Beta-blockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Comb 25 with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding,
ask your doctor or pharmacist for advice before using this medicine.
Inform your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Comb 25 in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the insulin dose and
diet may be necessary.

Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. 360

Take into account the possibility that this may occur in all situations where you could pose a
risk to yourself and others (such as driving a car or using machinery). Ask your
doctor for advice if you should drive if:

• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 25
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 25

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycemia), your doctor will:

• establish the daily amount of Insuman Comb 25 you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Comb 25 is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Comb 25 is injected subcutaneously 30 – 45 minutes before a meal.

Method of administration
Insuman Comb 25 is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Comb 25 into a vein (blood vessel).
The doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Comb 25 in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the vials
Insuman Comb 25 contains 100 IU of insulin per ml. Only injection syringes suitable for this
concentration (100 IU per ml) must be used. Injection syringes must not contain other
medicines or their residues (such as traces of heparin).
Before drawing up the insulin for the first time, you must remove the tear-off safety cap
from the vial.
Immediately before each injection, mix the insulin well. To do this, rotate the vial diagonally
between the palms of your hands. Do not shake the vial vigorously because this may damage the insulin and cause foaming. Foam may
interfere with accurate dose measurement.
After mixing, the liquid should appear uniformly milky. It should not be used if the
suspension remains clear or, for example, if small lumps, particles or flakes form inside or on the wall or bottom of the vial. In these cases, another vial should be used, the contents of which have a uniform appearance.
Always use a new vial if you notice that your blood sugar control has
unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you think
you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Special precautions before the injection
Air bubbles must be removed before the injection. Make sure that neither alcohol nor other disinfectants
nor other contaminating substances contaminate the insulin. Do not mix the insulin with other medicines, with the exception of the
human insulin formulations listed below.
Insuman Comb 25 can be mixed with all human insulin formulations, EXCEPT those
specifically intended for use in insulin pumps. Also, DO NOT mix with animal insulins or insulin analogues.
The doctor will tell you if it is necessary to mix human insulins. If it is necessary to inject a mixture, draw the other
insulin into the injection syringe before Insuman Comb 25. Proceed with the injection immediately after
mixing. Do not mix insulins of different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 25 than you should

• -If you have injected too high a dose of Insuman Comb 25, your blood sugar levels may become too low (hypoglycemia). Check your blood sugar frequently. In general, to prevent hypoglycemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycemia, see the box at the end of this leaflet.

If you forget to use Insuman Comb 25

• If you have forgotten a dose of Insuman Comb 25or have not injected enough insulin, your blood sugar levels may become too high (hyperglycemia). Check your blood sugar frequently. For information on treating hyperglycemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Comb 25
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (build-up
of acid in the blood because the body is metabolizing fat instead of sugar). Do not stop Insuman
Comb 25 without consulting a doctor who will tell you what is necessary to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicine between
Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
362
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most common side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For more information about the side effects of low blood sugar or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which could be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with a rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Changes in the skin at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site, or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.
363

5. How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the vial label
after “Expiry”/ “Exp”. The expiry date refers to the last day of that month.
Unused vials:
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Comb 25 in direct contact with the
freezer compartment or with cooling packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials:
Once in use, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C, protected from a direct source of heat (e.g. radiator) or from direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to eliminate the
medicines that you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Comb 25 contains

• The active ingredient is human insulin. 1 ml of Insuman Comb 25 contains 100 IU (International Units) of the active ingredient human insulin. 25% of the insulin is dissolved in water; the remaining 75% is present as fine crystals of protamine insulin.
• The other components are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about some components of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Comb 25 and contents of the pack
After mixing, Insuman Comb 25 is a uniformly milky liquid (injectable suspension),
without clumps, flakes or visible particles.
Insuman Comb 25 is supplied in vials containing 5 ml of suspension (500 IU). Packs of 1 and 5 vials of 5 ml are available.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the marketing authorisation
holder.

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)
364

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525
365

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, redness of the face, loss of appetite,
lowering of blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do in case of hyperglycemia?
Check your blood sugar and the possible presence of ketones in your
urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, generally in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognize when your blood sugar levels are dropping too low, so
you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,

366

• you are not eating enough or the food consumed contains less carbohydrates than usual (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggressiveness, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), sensations of tingling and numbness in the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood sugar levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin like Insuman,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognizing it in time. Therefore, learn to recognize the warning symptoms of hypoglycemia. If necessary, more frequent blood sugar checks may help identify mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning symptoms of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do in case of hypoglycemia?
367

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a long-lasting release of sugar into the blood (such as bread or pasta). Your doctor or nurse should have discussed these measures with you beforehand.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it occurs again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure whether a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
368

Insuman Comb 25 40 UI/ml injectable suspension in a vial

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 25 is and what it is used for
• 2. What you need to know before you use Insuman Comb 25
• 3. How to use Insuman Comb 25
• 4. Possible side effects
• 5. How to store Insuman Comb 25
• 6. Contents of the pack and other information

1. What is Insuman Comb 25 and what is it used for

Insuman Comb 25 contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 25 is an insulin preparation with a gradual onset of action and a long duration of action.
Insuman Comb 25 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 25

Do not use Insuman Comb 25
If you are allergic (hypersensitive) to insulin or any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Insuman Comb 25.
Follow the instructions given to you by your doctor regarding the dose, checks to be performed (on blood
and urine), diet and physical activity (work and exercise) very carefully.
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Skin changes at the injection site:
369
The injection site must be rotated to prevent skin changes, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Comb 25). If you are currently injecting into an area with
nodules, talk to your doctor before starting to inject into another area. Your doctor may
ask you to check your blood sugar more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Consult your doctor before starting a trip. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, syringes, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of changing time zones,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Butmilk and injuries
In the following situations, blood sugar control may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to inform people close to you about your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or localized
swelling (edema).

Other medicines andInsuman Comb 25
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes,
• angiotensin converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase inhibitors (MAO) (used to treat depression), 370
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that acts on ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• betablockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Betablockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Comb 25 with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Comb 25 in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the dose of insulin and
diet may be necessary.

Driving and operating machinery
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. 371

Take into account the possibility that this may occur in all situations where you could pose a
risk to yourself and others (such as driving a car or using machinery). Ask your
doctor for advice on whether it is appropriate for you to drive if:

• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Comb 25
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 25

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycemia), your doctor will:

• establish the daily amount of Insuman Comb 25 you need,
• inform you of when you should check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Comb 25 is necessary.

Many factors can influence your blood sugar levels. It is advisable that you are aware of these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Comb 25 is injected subcutaneously 30 – 45 minutes before a meal.

Method of administration
Insuman Comb 25 is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Comb 25 into a vein (blood vessel).
Your doctor will indicate which area of the skin you should inject the insulin into. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Comb 25 in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the vials
Insuman Comb 25 contains 40 IU of insulin per ml. Only syringes for injection suitable for this
concentration (40 IU per ml) must be used. The injection syringes must not contain other
medicines or their residues (such as traces of heparin).
Before drawing the insulin for the first time, you must remove the tear-off safety cap
from the vial.
Immediately before each injection, mix the insulin well. To do this, rotate the vial diagonally
between the palms of your hands. Do not shake the vial vigorously because this may damage the insulin and cause foaming.
Foam may interfere with accurate dose measurement.
After mixing, the liquid should appear uniformly milky. It should not be used if the
suspension remains clear or, for example, if small lumps, particles or flakes or similar form
inside or on the wall or bottom of the vial. In these cases, another vial should be used, the contents of which have a uniform appearance.
Always use a new vial if you notice that your blood sugar control has
unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you think
you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Special precautions before the injection
Air bubbles must be removed before the injection. Make sure that neither alcohol nor other disinfectants
nor other contaminating substances contaminate the insulin. Do not mix the insulin with other medicines, except for the
human insulin formulations listed below.
Insuman Comb 25 can be mixed with all human insulin formulations, EXCEPT those
specifically intended for use in insulin pumps. Also, DO NOT mix with animal insulins or insulin analogs.
Your doctor will tell you if it is necessary to mix human insulins. If it is necessary to inject a mixture, draw the other
insulin into the injection syringe before Insuman Comb 25. Proceed with the injection immediately after
mixing. Do not mix insulins with different concentrations (e.g. 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 25 than you should

• -If you have injected too high a dose of Insuman Comb 25, your blood sugar levels may become too low (hypoglycemia). Check your blood sugar frequently. In general, to prevent hypoglycemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycemia, see the box at the end of this leaflet.

If you forget to use Insuman Comb 25

• If you have forgotten a dose of Insuman Comb 25or have not injected enough insulin, your blood sugar levels may become too high (hyperglycemia). Check your blood sugar frequently. For information on treating hyperglycemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Insuman Comb 25
This can lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (build-up
of acid in the blood because the body is metabolizing fat instead of sugar). Do not stop Insuman
Comb 25 without consulting a doctor who will tell you what you need to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicine between
Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
373
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with frequency not known(cannot be estimated from the available data)

• The most common side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For more information about the side effects of low blood sugar or high blood sugar levels, see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which could be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with frequency not known

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily impair vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Changes in the skin at the injection site: If you inject insulin too often in the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis: it is not known how often this occurs). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site, or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only rarely does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
374
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the vial label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Unused vials:
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Comb 25 in direct contact with the
freezer compartment or with refrigerant packs. Store the vial in the outer packaging to
protect the medicine from light.
Opened vials:
Once in use, the vial can be stored for a maximum of 4 weeks at a temperature not
exceeding 25°C, protected from a direct source of heat (e.g. radiator) or from direct light (direct sunlight or lamp) in the outer packaging. Do not use the vial after this period. It is recommended to
write the date of first use on the label itself.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Insuman Comb 25 contains

• The active ingredient is human insulin. 1 ml of Insuman Comb 25 contains 40 IU (International Units) of the active ingredient human insulin. 25% of the insulin is dissolved in water; the remaining 75% is present as fine crystals of protamine insulin.
• The other components are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Comb 25 and contents of the pack
After mixing, Insuman Comb 25 is a uniformly milky liquid (injectable suspension),
without clumps, flakes or visible particles.
Insuman Comb 25 is supplied in vials containing 10 ml of suspension (400 IU). Packs of 1 and 5 vials of 10 ml are available.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicine, contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40
375

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi România SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical questions)
800 536389 (other questions)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300
376

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.

Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
low blood pressure, rapid heartbeat and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
Check your blood sugar and the presence of ketones in your
urine as soon as possible if you experience any of the symptoms reported above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
377
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognize when your blood sugar levels are dropping too low, so
you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains less carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of insulin treatment or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning signs of hypoglycemia

• In the body Examples of symptoms that indicate that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms that indicate a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggressiveness, difficulty concentrating, reduced ability to react, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), sensations of tingling and numbness in the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

378
In these cases, a severe hypoglycemia (even with loss of consciousness) can develop without
recognizing it in time. Therefore, learn to recognize the warning symptoms of hypoglycemia. If necessary, more frequent blood sugar checks may be helpful in identifying mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning symptoms of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. Then consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should discuss these measures with you beforehand.
• 3. If another hypoglycemia occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues who are close to you that:
If you are unable to swallow or lose consciousness, an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
379

Insuman Comb 25 100 UI/ml injectable suspension in a cartridge

Human insulin

Read this leaflet carefully before you start using this medicine as it contains important
information for you. Instructions for using the insulin pen are provided with your insulin pen.
Refer to these before using your medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 25 is and what it is used for
• 2. What you need to know before you use Insuman Comb 25
• 3. How to use Insuman Comb 25
• 4. Possible side effects
• 5. How to store Insuman Comb 25
• 6. Contents of the pack and other information

1. What is Insuman Comb 25 and what is it used for

Insuman Comb 25 contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 25 is an insulin preparation with a gradual onset of action and a long duration of action.
Insuman Comb 25 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a disease in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 25

Do not use Insuman Comb 25
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Comb 25 in cartridges is only suitable for subcutaneous injections with a reusable pen (see
also section 3). Talk to your doctor if you need to inject the insulin using a different method.
Contact your doctor, pharmacist or nurse before using Insuman Comb 25.
Follow the instructions given to you by your doctor strictly regarding the dose, checks to be performed (blood
and urine), diet and physical activity (work and exercise).
Tell your doctor if you are allergic to this medicine or to animal insulins.
380
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Skin changes at the injection site:
The injection site must be rotated to prevent skin changes, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject into an area with
nodules (see section How to use Insuman Comb 25). If you are currently injecting into an area with
nodules, contact your doctor before starting to inject into another area. Your doctor may
advise you to check your blood glucose more carefully and adjust the dose of insulin or other antidiabetic
medicines.
Travel
Before starting a trip consult your doctor. You may need to discuss the following aspects:

• availability of insulin in the destination country,
• sufficient supplies of insulin, needles, etc.,
• correct storage of insulin during the trip,
• interval between meals and insulin administration during the trip,
• possible effects of the time zone change,
• possible risks of contracting new diseases in the countries visited.
• what to do in emergency situations if you do not feel well or become ill.

Illnesses and injuries
In the following situations, control of diabetes may require close attention:

• If you are ill or have serious injuries, there is a risk that your blood sugar level will increase (hyperglycemia).
• If you do not eat enough, there is a risk that your blood sugar level will decrease (hypoglycemia). In most cases, medical intervention is necessary. Contact your doctor quickly.

Also, if you suffer from type 1 diabetes (insulin-dependent diabetes mellitus), do not stop treatment with
insulin or the intake of carbohydrates. It is necessary to keep people close to you informed of your
need for insulin.
Some patients with long-lasting type 2 diabetes mellitus and heart disease or with a previous stroke,
treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible
if you have signs of heart failure such as unusually short breath or rapid weight gain or localized swelling (edema).

Other medicines andInsuman Comb 25
Some medicines can cause changes in blood sugar levels (reduction or increase
or both depending on the situation). In any case, optimization of the insulin dose is necessary to
avoid blood sugar levels that are too low or too high. Be careful when starting or
stopping another medicine.
Tell your doctor or pharmacist if you are taking, have recently taken or may take any
other medicine. Before taking a medicine, ask your doctor if it can affect blood sugar and if
countermeasures are necessary.

Medicines that can cause a decrease in blood sugar levels (hypoglycemia)
include:

• all other medicines used to treat diabetes, 381
• angiotensin-converting enzyme (ACE) inhibitors (used to treat some heart conditions or high blood pressure),
• disopyramide (used to treat some heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to lower high levels of fats in the blood),
• monoamine oxidase (MAO) inhibitors (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),
• sulfonamide antibiotics.

Medicines that can cause an increase in blood sugar levels (hyperglycemia) include:

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat high blood pressure),
• diuretics (used to treat high blood pressure or excessive fluid retention),
• glucagon (pancreatic hormone used to treat severe hypoglycemia, i.e. low blood sugar levels),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as in the birth control pill used for contraception),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
• thyroid hormones (used to treat thyroid disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

• beta-blockers (used to treat high blood pressure),
• clonidine (used to treat high blood pressure),
• lithium salts (used to treat psychiatric disorders). Pentamidine (used to treat some infections caused by parasites) can cause hypoglycemia, sometimes followed by hyperglycemia.

Beta-blockers as well as other sympatholytic medicines (such as clonidine, guanethidine and reserpine) can
reduce or completely cancel the warning signs that help you recognize hypoglycemia.
If you are not sure if you are taking one of these medicines, ask your doctor or pharmacist.

Insuman Comb 25 with alcohol
Blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect or are planning a pregnancy, or if you are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before using this medicine.
Tell your doctor if you are planning a pregnancy or if you are already pregnant. It may be
necessary to adjust the dose of insulin during pregnancy and after delivery. It is important to control
diabetes carefully and prevent hypoglycemia for the health of the baby. However, there is no experience with
the use of Insuman Comb 25 in pregnancy.
If you are breastfeeding, consult your doctor, as adjustments to the dose of insulin and
diet may be necessary.
382

Driving and using machines
Your ability to concentrate or react may be reduced in case of:

• hypoglycemia (low blood sugar levels),
• hyperglycemia (high blood sugar levels),
• vision problems. Take into account the possibility that this may occur in all situations where you could pose a risk to yourself and others (such as driving a car or using machinery). Ask your doctor for advice on whether you should drive if:
• you have frequent hypoglycemic attacks,
• the typical signs that help you identify hypoglycemia are reduced or absent.

Important information about some ingredients of Insuman Comb 25
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 25

Dose
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
Based on your lifestyle and the results of tests for your blood sugar level (glycaemia), your doctor will:

• establish the daily amount of Insuman Comb 25 you need,
• inform you of when you must check your blood sugar and, if necessary, when to perform urine tests,
• inform you if a lower or higher dose of Insuman Comb 25 is necessary.

Many factors can influence your blood sugar levels. It is advisable that you know these
factors so that you can act appropriately in case of changes in blood sugar levels and
thus avoid them becoming too high or too low. For further information, see the box
at the end of this leaflet.

Frequency of administration
Insuman Comb 25 is injected subcutaneously 30 – 45 minutes before a meal.

Method of administration
Insuman Comb 25 is a liquid (suspension) for subcutaneous injection.
DO NOT inject Insuman Comb 25 into a vein (blood vessel).
Your doctor will tell you in which area of the skin you should inject the insulin. For each injection, change the injection site
within the chosen skin area.
Do not use Insuman Comb 25 in insulin pumps - special insulin preparations are available for use with such devices.

How to handle the cartridges
Insuman Comb 25 in cartridges is only suitable for subcutaneous injections with a reusable pen. Talk
to your doctor if you need to inject insulin in another way.
To ensure the administration of the correct dose, the Insuman Comb 25 cartridges must be
used only with the following pens:
383

• JuniorStar for the administration of Insuman Comb 25 with dose increments of 0.5 units
• ClikSTAR, Tactipen, Autopen 24 AllStar or AllStar PRO for the administration of Insuman Comb 25 with dose increments of 1 unit. It is possible that not all pens are marketed in your country.

The pens must be used as recommended in the information provided by the
device manufacturer. Carefully follow the manufacturer's instructions for loading the cartridge, inserting the injection needle and administering
the insulin injection. It is recommended to store the cartridge at room temperature for 1 or 2 hours before inserting it into the pen.
Mix the insulin well and check it before inserting it into the pen. Afterwards, the insulin must always be
mixed very well immediately before each injection.
Mixing is best done by gently tilting the cartridge or pen (with the
cartridge inserted) back and forth at least 10 times. To facilitate mixing, each cartridge contains three small metal balls.
After mixing, the liquid should appear uniformly milky. It should not be used if the
suspension remains clear or, for example, if small lumps, particles or flakes or similar form
inside it or on the wall or bottom of the cartridge. In these cases, another cartridge should be used whose
contents have a uniform appearance.
Always use a new cartridge if you notice that your blood sugar control has
unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you think
you may have a problem with the insulin, have it checked by your doctor or pharmacist.

Special precautions before injection
Air bubbles must be removed before injection (see the instructions for using the pen).
Make sure that neither alcohol nor other disinfectants or other contaminating substances get into the insulin.

• Do not refill or reuse empty cartridges.
• Do not add other insulins to the cartridges.
• Do not mix the insulin with other medicines.

Problems with the pen?
Refer to the manufacturer's instructions for using the pen.
If the insulin pen is damaged or does not function properly (due to mechanical
defects) it must be discarded and a new insulin pen must be used.
If you use more Insuman Comb 25 than you should

• If you have injected too high a dose of Insuman Comb 25, your blood sugar levels may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia, you should eat more substantial meals and check your blood sugar. For information on treating hypoglycaemia, see the box at the end of this leaflet.

If you forget to use Insuman Comb 25

• If you have forgotten a dose of Insuman Comb 25or have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for a missed dose.

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If you stop treatment with Insuman Comb 25
This can lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of
acid in the blood because the body is metabolising fat instead of sugar). Do not stop Insuman
Comb 25 without consulting a doctor who will tell you what you need to do.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse.

Insulin exchanges
You should always check the insulin label before each injection to avoid exchanging medicines between
Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
More serious side effects

Side effects reported uncommonly(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Side effects reported with unknown frequency(cannot be estimated from the available data)

• The most frequent side effect is hypoglycemia(low blood sugar levels). Severe hypoglycemic episodes can cause heart attack or brain damage and can be life-threatening. For further information on the side effects of low blood sugar levels or high blood sugar levels see the box at the end of this leaflet.
• Severe, widespread allergic reactions to insulincan occur, which may be life-threatening. Such reactions to insulin or excipients can cause extensive skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating

Other side effects

Side effects reported commonly(may affect up to 1 in 10 people)

• Edema Treatment with insulin can lead to temporary increased fluid retention in the body with swelling in the calf and ankle areas.
• Reactions at the injection site

Side effects reported uncommonly

• Urticaria at the injection site (itchy rash)

Side effects reported with unknown frequency

• Sodium retention
• Eye reactions A marked change (improvement or worsening) in blood sugar levels can temporarily disturb vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycemic episodes can cause temporary loss of vision.
• Skin changes at the injection site: If you inject insulin too often into the same place, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin can also be caused by the build-up of a protein called amyloid (cutaneous amyloidosis: how often this occurs is not known). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes. 385
• Skin and allergic reactions Other mild reactions may occur at the injection site (such as redness at the injection site, unusually intense pain at the injection site, itching, swelling at the injection site or inflammation at the injection site). These disturbances can spread around the injection site. Most minor reactions to insulin resolve within a few days or within a few weeks.
• Anti-insulin antibodies Treatment with insulin can lead to the formation of anti-insulin antibodies (substances that act against insulin). Only in rare cases does the presence of such antibodies require an adjustment of the insulin dose.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly through the
national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the cartridge label
after “Scad”/ “Exp”. The expiry date refers to the last day of that month.
Cartridges not in use
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not place Insuman Comb 25 in direct contact with the
freezer compartment or with cooling packs. Store the cartridge in the outer packaging to
protect the medicine from light.
Cartridges in use
Cartridges in use (in the insulin pen) or kept as “spare”, can be stored for a maximum
of 4 weeks at a temperature not exceeding 25°C, protected from a direct source of heat (e.g.
radiator) or from direct light (direct sunlight or lamp). The cartridge in use must not be stored in
the refrigerator. Do not use the cartridge after this period.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to eliminate the
medicines that you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 25 contains

• The active substance is human insulin. 1 ml of Insuman Comb 25 contains 100 IU (International Units) of the active substance human insulin. 25% of the insulin is dissolved in water; the remaining 75% is present as fine crystals of protamine insulin.
• The other ingredients are: protamine sulfate, meta-cresol, phenol, zinc chloride, disodium phosphate dihydrate, glycerol, sodium hydroxide (see section 2 in “Important information about certain components of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Insuman Comb 25 and contents of the pack
After mixing, Insuman Comb 25 is a uniformly milky liquid (injectable suspension),
without clumps, flakes or visible particles.
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Insuman Comb 25 is supplied in cartridges containing 3 ml of suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany.
For further information on this medicinal product, contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis AEBE
Τηλ: +30 210 900 16 00

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400
387

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi România SRL
Tel: +40 (0) 21 317 31 36

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 13 12 12 (technical inquiries)
800 536389 (other inquiries)

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

HYPERGLYCEMIA AND HYPOGLYCEMIA
Always carry some sugar with you (at least 20 grams).
Carry information indicating that you have diabetes.
HYPERGLYCEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycemia),you may not have injected
enough insulin.
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Why does hyperglycemia occur?
Examples include:

• you did not inject insulin or administered an insufficient amount, or when the insulin becomes less effective (e.g. because it was not stored correctly),
• the insulin pen is not working correctly,
• you are doing less exercise than usual, or are particularly stressed (emotionally or physically), or in cases of injury, surgery, infection or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

Warning signs of hyperglycemia
Thirst, increased need to urinate, weakness, dry skin, flushing of the face, loss of appetite,
low blood pressure, rapid heartbeat, and the presence of glucose or ketones in the urine.
Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may
indicate a serious condition (ketoacidosis) resulting from insulin deficiency.

What should you do if you have hyperglycemia?
Check your blood sugar and the presence of ketones in your urine as soon as possible if you experience any of the symptoms mentioned above.Severe hyperglycemia or ketoacidosis
must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycemic episodes
can cause heart attack or brain damage and can be life-threatening. Generally, you
should be able to recognise when your blood sugar levels are dropping too low, so
you can take appropriate precautions.

Why does hypoglycemia occur?
Examples include:

• you injected too much insulin,
• you skipped or delayed meals,
• you are not eating enough or the food consumed contains a lower amount of carbohydrates than normally consumed (carbohydrates are sugar and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
• you have lost carbohydrates due to vomiting or diarrhoea,
• you drink alcoholic beverages, especially if you are eating little,
• you are doing more exercise than usual, or a different type of activity,
• you are recovering from injury, surgery or stress,
• you are recovering from an illness or fever,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

Hypoglycemia can also occur more easily if:

• you are at the beginning of treatment with insulin or have switched to a different type of insulin,
• your blood sugar levels are almost normal or show variations,
• you have changed the area of skin where you inject the insulin (e.g. from the thigh to the upper arm),
• you suffer from severe kidney or liver disease, or other diseases such as hypothyroidism.

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Warning signs of hypoglycemia

• In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms can often develop before those indicating a reduction in brain sugar levels.
• In the brain Examples of symptoms indicating a reduction in brain sugar levels: headache, insatiable hunger, nausea, vomiting, fatigue, sleepiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced ability to react, depressed mood, confusion, speech difficulties (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paresthesia), sensations of tingling and numbness in the mouth, dizziness, loss of self-control, inability to care for oneself, convulsions, loss of consciousness.

The early characteristic symptoms of a state of hypoglycemia ("warning symptoms") may vary, be
less noticeable or even completely absent if:

• you are elderly, have had diabetes for a long time or suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
• after a recent hypoglycemic episode (e.g. the day before) or if hypoglycemia appears slowly,
• blood glucose levels are almost normal or at least significantly improved,
• you have recently switched from animal insulin to human insulin such as Insuman,
• you are taking or have taken certain other medicines (see section 2, “Other medicines and Insuman Comb 25”).

In these cases, a severe hypoglycemia (even with loss of consciousness) may develop without
recognising it in time. Therefore, learn to recognise the warning signs of hypoglycemia. If necessary, more frequent blood glucose checks may be helpful in identifying mild hypoglycemic episodes that might otherwise go unnoticed. If you are unable to recognise the warning signs of hypoglycemia, avoid all those situations (such as driving a car) that may be
risky for you and others due to hypoglycemia.

What should you do if you have hypoglycemia?

• 1. Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugar-sweetened drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycemia.
• 2. At this point, consume food that can cause a release of sugar into the blood for a long period of time (such as bread or pasta). Your doctor or nurse should have discussed these measures with you beforehand.
• 3. If another hypoglycemic episode occurs, take another 10 to 20 g of sugar again.
• 4. Talk to your doctor as soon as you notice an inability to control hypoglycemia or if it happens again.

Inform your relatives, friends and colleagues close to you that:
If you are unable to swallow or lose consciousness, an injection of glucose or
glucagon (a medicine that increases blood sugar levels) is necessary. These injections are justified
even if you are not sure that a hypoglycemic event has occurred.
It is advisable to check blood sugar immediately after taking sugar to confirm
that a hypoglycemic episode was occurring.
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Insuman Comb 25 SoloStar 100 IU/ml injectable suspension in a pre-filled pen

Human insulin

Read this leaflet carefully, including the instructions for use of the Insuman Comb 25 SoloStar pre-filled pen, before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Insuman Comb 25 is and what it is used for
• 2. What you need to know before you use Insuman Comb 25
• 3. How to use Insuman Comb 25
• 4. Possible side effects
• 5. How to store Insuman Comb 25
• 6. Contents of the pack and other information

1. What is Insuman Comb 25 and what is it used for

Insuman Comb 25 contains the active ingredient human insulin, which is produced by a biotechnological process and is identical to the insulin found in our body.
Insuman Comb 25 is an insulin preparation with a gradual onset of action and a long duration of action.
It is available in cartridges contained in a disposable SoloStar pen injector.
Insuman Comb 25 is used to lower high blood sugar levels in patients with
diabetes mellitus who require insulin supplementation. Diabetes mellitus is a condition in which the body
does not produce enough insulin to control blood sugar levels.

2. What you need to know before using Insuman Comb 25

Do not use Insuman Comb 25
If you are allergic (hypersensitive) to insulin or to any of the other ingredients of this medicine
(listed in section 6).

Warnings and precautions
Insuman Comb 25 in a prefilled pen is only suitable for subcutaneous injections (see also section
3). Talk to your doctor if you need to inject the insulin in a different way.
Consult your doctor, pharmacist or nurse before using Insuman Comb 25.
Follow strictly the instructions given to you by your doctor regarding the dose, the checks to be performed (on blood
and urine), diet and physical activity (work and exercise), injection technique.
391
Tell your doctor if you are allergic to this medicine or to animal insulins.
Special patient groups
If you have liver or kidney problems, or if you are elderly, consult your doctor because you may need a lower
dose.
Skin changes at the injection site:
The injection site must be rotated to prevent skin changes, such as the appearance of nodules
under the skin. Insulin may not work as well as it should if you inject it into an area with
nodules (see section How to use Insuman Comb 25). If you are currently injecting into an area with
nodules, consult your doctor before starting to inject into another area. Your doctor may
advise you to check your blood sugar more carefully and adjust your insulin or other antidiabetic
medicines.
Travel
Before starting a trip, consult your doctor. You may need to discuss the following aspects: