INCRELEX 10 mg /Ml Roztwór Do Wstrzykiwań

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1. INCRELEX 10 mg/ml injectable solution
   1. What is INCRELEX and what is it used for
   2. What you need to know before using INCRELEX:
   3. How to use INCRELEX
   4. Possible side effects
   5. How to store INCRELEX
   6. Contents of the pack and other information

INCRELEX 10 mg/ml injectable solution

Mecasermina

Medicinal product subject to additional monitoring. This will allow the rapid identification of new safety information. You can contribute by reporting any adverse effects encountered during the use of this medicine. See the end of section 4 for information on how to report adverse effects.

Read this leaflet carefully 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 or pharmacist.
• This medicine has been prescribed for you only. Never give it to others. Indeed, this medicine may be dangerous for other individuals, even if their symptoms of illness are the same as yours.
• If any adverse effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is INCRELEX and what is it used for

• INCRELEX is a liquid that contains mecasermin which is an insulin-like growth factor of type I (IGF-1) produced artificially, which is similar to the IGF-1 produced normally by the human body.
• It is used to treat children and adolescents from 2 to 18 years of age who have very short stature for their age because their body does not produce enough IGF-1. This condition is called primary IGF-1 deficiency.

2. What you need to know before using INCRELEX:

Do not take INCRELEX:

• If you have any tumor or growth, whether cancerous or non-cancerous
• If you have had cancer in the past
• If you have any condition that may increase the risk of cancer
• if you are allergic to mecasermin or any of the excipients of this medicine (listed in section 6)
• in premature or newborn infants as the medicine contains benzyl alcohol.

Warnings and precautions
In children and adolescents treated with INCRELEX, there is an increased risk of tumors and growth (both
cancerous and non-cancerous). Immediately report to your competent medical specialist if any
new growth, skin lesion or any unexpected symptom should occur during or after treatment, as
mecasermin may play an important role in the development of cancer.
Consult your doctor or pharmacist before using INCRELEX:

• if you have a curved spine (scoliosis): you must undergo monitoring to assess the progression of scoliosis.
• if you develop limping or pain in the hip or knee
• if you have enlarged tonsils (tonsillar hypertrophy): in this case you must undergo periodic appropriate assessments.
• if you experience symptoms of increased intracranial pressure (intracranial hypertension), such as changes in vision, headache, nausea and/or vomiting, ask your doctor for advice.
• ask your doctor if you have a localized reaction at the injection site or a generalized allergic reaction to INCRELEX. Contact your doctor as soon as possible if you have a localized rash. Seek immediate medical help if you have a generalized allergic reaction (hives, breathing problems, feeling unwell or collapse and in case of general malaise).
• if you have stopped growing (the epiphyseal growth cartilages are closed). In this case INCRELEX cannot promote growth and should not be used.

Children under 2 years of age
The use of this medicine has not been studied in children under 2 years of age and therefore should not
be used in these subjects.

Other medicines and INCRELEX:
Tell your doctor or pharmacist if you are taking or have recently taken or may take
any other medicine.
In particular, tell your doctor if you are taking insulin or other antidiabetic medicines. An
adjustment of the doses may be necessary for all these medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect or are planning a pregnancy or if you are breastfeeding with breast
milk, ask your doctor for advice before taking this medicine .
For all women of childbearing potential, negative pregnancy tests are recommended before treatment with mecasermin.
It is also recommended that all women of childbearing potential use adequate contraception.
Therapy with mecasermin should be discontinued in case of pregnancy.
Mecasermin should not be administered to a breastfeeding mother.

Driving and operating machinery
Mecasermin can cause hypoglycemia (very common undesirable effect, see section 4) which may
impair the ability to drive and operate machinery because concentration and
reaction abilities may be reduced.
You should avoid activities that require a high degree of attention (e.g. driving and others) for 2-3 hours after
taking the dose, especially at the beginning of treatment with INCRELEX, until a
dose of INCRELEX is found that does not cause the onset of side effects that may
make these activities risky.

INCRELEX contains benzyl alcohol and sodium
INCRELEX contains benzyl alcohol as a preservative, which can cause toxic reactions and allergic
reactions in newborns and children up to 3 years of age.
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially
“sodium-free”.

3. How to use INCRELEX

Use this medicine following the instructions of your doctor exactly. If you have any doubts, consult your
doctor or pharmacist.
The usual dose is between 0.04 and 0.12 mg/kg of the patient's weight administered twice a day.
Inject INCRELEX under the skin shortly before or shortly after a meal or snack because it may have
insulin-like hypoglycemic effects and therefore may reduce blood sugar levels (hypoglycemia
see section 4). Do not administer the dose of INCRELEX if you are unable to eat for any
reason. If a dose is missed, do not compensate for the forgetfulness by using two doses next time.
The next dose should be taken as usual, with a meal or snack.
Inject INCRELEX under the skin of the arm, thigh, stomach area (abdomen) or
buttocks. Change the injection site with each injection. Never inject it into a vein or a muscle.
Use INCRELEX only if it is clear and colorless.
Treatment with mecasermine is a long-term therapy. For more information, contact your
doctor.

If you take more INCRELEX than you should
Mecasermine, like insulin, can reduce blood sugar levels (see hypoglycemia in
section 4).
If more INCRELEX than recommended is injected, inform your doctor immediately.
Acute overdose can lead to hypoglycemia (low blood sugar).
Treatment of acute mecasermine overdose should be aimed at reversing hypoglycemia.
Sugary liquids or foods should be taken. If the patient is not conscious or
sufficiently alert to drink sugary liquids, an injection
intramuscular glucagon may be needed to reverse low blood sugar levels. Your doctor or nurse will
tell you how to administer the glucagon injection.
In the long term, overdose can cause enlargement of certain parts of the body (e.g.,
hands, feet, parts of the face) or excessive growth of the whole body. If you suspect a long-term overdose
, contact your doctor immediately.

If you forget to take INCRELEX
Do not take a double dose to make up for a missed dose.
If a dose is missed, the next dose should not be higher to compensate. The next dose should be taken as usual, with a meal or snack.

If you stop taking INCRELEX
Stopping or prematurely terminating treatment with mecasermine may compromise the effectiveness
of growth therapy. Ask your doctor for advice before stopping treatment.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you get any side effect, talk to your doctor or pharmacist. The most common side effects with mecasermina are: low blood sugar
(hypoglycemia), vomiting, reactions at the injection site, headache and middle ear infections. Serious allergic reactions have also been reported with INCRELEX. If any of these events occur, please
follow the advice provided for each event in the sections below.

Not known frequency (the frequency cannot be estimated from available data)
Cancerous and non-cancerous tumors
In patients treated with INCRELEX, an increased risk of cancerous and non-cancerous tumors has been observed. The risk of these tumors may be higher if INCRELEX is used for indications
other than those indicated in paragraph 1 or used at doses higher than those recommended in paragraph

• 3.

Serious allergic reactions (anaphylaxis)
Generalized hives, difficulty breathing, dizziness, swelling of the face and/or throat have been reported following the use of mecasermina. Stop using INCRELEX immediately and
consult a doctor urgently if a serious allergic reaction develops. Local allergic reactions at the injection site (itching, hives) have also been reported.
Hair loss (alopecia)
Hair loss has also been reported after the use of mecasermina

Very common (may affect more than 1 in 10 people)
Low blood sugar (hypoglycemia)
Mecasermina can lower blood sugar levels. Signs of low blood sugar are: dizziness, tiredness, restlessness, hunger, irritability, difficulty concentrating,
sweating, nausea and fast or irregular heartbeat.
Severe hypoglycemia can cause unconsciousness, convulsions/seizures or death. Stop administering INCRELEX immediately and consult a doctor urgently if
you develop convulsions/seizures or loss of consciousness.
If you are taking INCRELEX, you should avoid activities with a high risk (such as intense physical activity) within 2 or 3 hours after the injection of INCRELEX, especially at the beginning of treatment with
INCRELEX.
Before starting treatment with INCRELEX, your doctor or nurse will explain how to treat
hypoglycemia. You should always have a source of sugar such as orange juice, sugar gel, candies, or milk available in case of the onset of hypoglycemia symptoms. For severe hypoglycemia, if
you are unresponsive, and cannot drink liquids containing sugar, you should administer an injection of
glucagon. Your doctor or nurse will explain how to administer the injection. Glucagon increases
blood sugar when injected. It is important that you follow a well-balanced diet that includes
proteins and fats such as meat and cheese, in addition to the sugar contained in foods.
Blood glucose (glucose) should be monitored with a capillary blood test by pricking the fingertip before
each meal at the beginning of treatment and until a well-tolerated dose is established. If you
experience frequent symptoms of hypoglycemia or severe hypoglycemia, blood glucose monitoring
should continue regardless of whether or not you have eaten, and if possible, during episodes of
hypoglycemia.
Hypertrophy at the injection site (tissue swelling at the injection site) and bruising
This can be avoided by alternating the injection site with each administration (injection site rotation).
Gastrointestinal system
Vomiting and upper abdominal pain have occurred in patients treated with
mecasermina.
Infections
Middle ear infections have been observed in children treated with mecasermina.
Musculoskeletal system
Joint pain and limb pain have occurred during treatment with mecasermina.
Nervous system
Headache has occurred during treatment with mecasermina.

Common (may affect up to 1 in 10 people)
Convulsions
Convulsions (seizures) have been observed during treatment with mecasermina.
Dizziness and tremor have also been reported during treatment with mecasermina.
Cardiac disorders
Fast heartbeat and abnormal heart sounds have been reported during treatment with
mecasermina.
Increased blood sugar (hyperglycemia)
Increased blood sugar has been observed during treatment with mecasermina.
Tonsillar/adenoid hypertrophy
Mecasermina can cause the tonsils to enlarge. Some signs of tonsillar hypertrophy include:
snoring, difficulty breathing or swallowing, sleep apnea syndrome (a condition in which
breathing is briefly interrupted during sleep) or fluid in the middle ear and ear infections. Sleep apnea can cause excessive daytime sleepiness. Contact your
doctor if these symptoms bother you. The doctor should regularly examine the tonsils/adenoids.
Thymus enlargement
An enlargement of the thymus (an organ specialized in the immune system) has been observed during
treatment with mecasermina.
Papilledema
Swelling in the back of the eye (due to increased pressure inside the brain) can be observed by the doctor or optician during treatment with mecasermina.
Hearing loss (hearing impairment)
Hearing loss (hearing impairment), ear pain and fluid in the middle ear have been observed
during treatment with mecasermina. Tell your doctor if you develop hearing problems.
Worsening of scoliosis (caused by rapid growth)
If you have scoliosis, frequent checks are needed to monitor the progression and increase in
curvature of the spine. Muscle pain has also been observed with mecasermina treatment.
Reproductive system
Breast enlargement has been observed with mecasermina treatment.
Gastrointestinal system
Abdominal pain has occurred during treatment with mecasermina.
Changes in skin and appendages
Skin thickening, nevi and hair arrangement abnormalities have been observed during treatment
with mecasermina.
Reactions at the injection site
Pain, irritation, bleeding, bruising, redness and hardening have been reported during treatment with mecasermina. Reactions at the injection site
can be avoided by varying the injection site with each administration (injection site rotation).

Uncommon (may affect up to 1 in 100 people)
Increased pressure in the brain (intracranial hypertension)
INCRELEX can sometimes cause a temporary increase in pressure inside the brain. Symptoms of intracranial hypertension can include changes in vision, headache, nausea and/or
vomiting. Tell your doctor immediately if you experience any of these symptoms. The doctor may
check if intracranial hypertension is present. If it is present, the doctor may decide to temporarily reduce or stop mecasermina therapy. Therapy with mecasermina can be
restarted after the episode has ended.
Cardiac abnormalities
In some patients treated with mecasermina, an ultrasound examination of the heart (echocardiogram) has
shown an increase in the size of the heart muscle and abnormalities in the function of the heart valve.
The doctor may perform an echocardiogram before, during and after treatment with
mecasermina.
Reactions at the injection site
Skin rashes, swelling and fat deposits have been reported during treatment with mecasermina. Reactions at the injection site can be avoided by varying the injection site
with each administration (injection site rotation).
Weight gain
Weight gain has been observed during treatment with mecasermina.
Other uncommon side effects observed with mecasermina treatment include
depression, nervousness.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through
the national reporting system listed in Appendix V.
By reporting side effects you can help provide more information on the safety
of this medicine

5. How to store INCRELEX

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 packaging and on the label
after "EXP". The expiry date refers to the last day of the month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Store the vial in the outer packaging to protect it from light.
After first use, the vial can be stored for up to 30 days at 2°C – 8ºC.
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 INCRELEX contains

• The active substance is mecasermin. 1 ml contains 10 mg of mecasermin. Each vial contains 40 mg of mecasermin.
• The excipients are: benzyl alcohol, sodium chloride, polysorbate 20, glacial acetic acid, sodium acetate and water for injections (see section 2 “INCRELEX contains benzyl alcohol and sodium”).

Description of the appearance of INCRELEX and contents of the pack
INCRELEX is an injectable solution from colourless to slightly yellow and from clear to slightly
opalescent supplied in a glass vial closed with a stopper and a seal. The vial contains 4 ml
of solution.
Pack of one vial.

Marketing Authorisation Holder and manufacturer
Marketing Authorisation Holder:
Esteve Pharmaceuticals S.A.
Passeig de la Zona Franca 109 Planta 4
08038 Barcelona
Spain
Manufacturer:
Tjoapack Netherlands B.V.
Nieuwe Donk 9
4879 AC Etten-Leur
Netherlands
For further information on Increlex, contact the local representative of the marketing authorisation
holder.

België/Belgique/Belgien,
Luxembourg/Luxemburg
Esteve Pharmaceuticals SPRL België
/Belgique/Belgien
Tél/Tel: +32 479 98 92 88

Italia
Esteve Pharmaceuticals SRL
Tel: +39 345 9214959

Latvija
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

България
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Česká republika
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Hrvatska
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Lietuva
Esteve Pharmaceuticals S.A.
Tel. +34 93 446 60 00

Danmark, Norge, Suomi/Finland, Sverige,
Ísland
Esteve Pharmaceuticals S.A.
Sverige/Ruotsi/Svíþjóð
Tlf/Puh/Tel/Sími: +34 93 446 60 00

Magyarország
Esteve Pharmaceuticals S.A.
Tel.: +34 93 446 60 00

Deutschland, Österreich
Esteve Pharmaceuticals GmbH
Deutschland
Tel.: +49 30 338427-100

Nederland
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Eesti
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Polska
Esteve Pharmaceuticals S.A.
Tel.: +34 93 446 60 00

Ελλάδα, Κύπρος, Malta
Esteve Pharmaceuticals S.A.
Ελλάδα
Τηλ: +34 93 446 60 00

Portugal
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

España
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Slovenija
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

France
Esteve Pharmaceuticals S.A.S
Tél: +33 1 42 31 07 10

Slovenská republika
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Ireland, United Kingdom (Northern Ireland)
Esteve Pharmaceuticals S.A.
Ireland
Tel: +34 93 446 60 00

România
Esteve Pharmaceuticals S.A.
Tel/Тел.: +34 93 446 60 00
The marketing authorisation for this medicinal product has been granted under “exceptional circumstances”.
This means that, due to the rarity of the disease, complete information on this medicinal product is not yet available.
The European Medicines Agency will review any new information annually on

Other sources of information:
More detailed information on this medicine is available on the website of the European
Medicines Agency: http://www.emea.europa.eu/
Also, links to other websites on rare diseases and related therapeutic treatments are provided.
European Medicines Agency.
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INSTRUCTIONS FOR USE
INCRELEX must be administered with sterile, single-use syringes and needles for injection that can
be provided by your doctor or pharmacist or nurse. The volume of the syringes must be small enough to allow accurate withdrawal of the dose from the vial.

Preparation of the dose:

• 1. Wash your hands before preparing INCRELEX for injection.
• 2. Use a new, single-use needle and syringe each time you administer a dose. Use syringes and needles only once. Dispose of them appropriately in a suitable sharps container (e.g. a biological risk container), a rigid plastic container (e.g. a detergent bottle), or a metal container (e.g. an empty coffee container). Do notshare needles and syringes.
• 3. Check the liquid to make sure it is clear and colourless. Do not use the medicine after the expiry date (which is stated on the label and refers to the last day of the month) or if the liquid is cloudy or if you notice particles. If the vial has been frozen, discard it appropriately. Ask your pharmacist how to dispose of the medicine that will no longer be used.
• 4. If you are using a new vial, remove the protective cap. Do not remove the rubber stopper.
• 5. Clean the rubber stopper of the vial with a swab moistened with alcohol to prevent contamination of the vial by germs that may be introduced through repeated needle insertions (see Figure 1).

Figure 1: clean the
top with alcohol

• 6. Before inserting the needle into the vial, pull back the plunger to draw an amount of air into the syringe equal to the prescribed dose. Insert the needle through the rubber stopper at the top of the vial and push the plunger to inject the air into the vial (see Figure 2).

• 7. Leave the syringe in the vial and turn them upside down. Hold the syringe and vial firmly (see Figure 3). Figure 2: inject air into the vial

Figure 3: prepare
the aspiration

• 8. Make sure the needle tip is in the liquid (see Figure 4). Pull the plunger to draw the correct dose into the syringe (see Figure 5).

• 9. Before removing the needle from the vial, check the syringe to make sure there are no air bubbles. If there are bubbles in the syringe, hold the vial and syringe with the needle pointing upwards and tap the side of the syringe until the bubbles rise to the surface. Push the bubbles out with the plunger and draw the liquid into the syringe until you have the correct dose (see Figure 6). Figure 5: draw the correct dose Figure 4: tip in the liquid

Figure 6: remove air bubbles
and refill the syringe

• 10. Remove the needle from the vial and replace the protective cap. Avoid touching anything with the needle. At this point you are ready for the injection (see Figure 7).

Injection of the dose:
Inject INCRELEX as prescribed by your doctor.
Do not administer the dose if you are unable to eat a little before or after the injection.

• 1. Choose the injection area – arm, thigh, buttock or abdomen (see below). The injection site should be changed with each injection (injection site rotation) to avoid the formation of a build-up of fatty tissue under the skin (lipohypertrophy) caused by repeated injections in the same place. Figure 7: ready for injection

• 2. Use alcohol or soap and water to clean the skin where you will inject the medicine. The injection site must be dry before the injection.
• 3. Pinch the skin lightly. Insert the needle as directed by your doctor. Release the skin (see Figure A). Arm Thigh Buttock Abdomen

• 4. Slowly push the syringe plunger all the way down, making sure you have injected all the liquid. Remove the needle and gently press the injection site with a gauze or cotton ball for a few seconds. Do not rub the area(see Figure B). Figure A: pinch the skin lightly and inject as directed by your doctor

• 5. Follow your doctor's instructions for disposing of the needle and syringe. Do not put the cap back on the syringe. Used syringes and needles should be placed in appropriate containers (such as a sharps container), a rigid plastic container (such as a detergent bottle) or a metal container (such as an empty coffee container). These containers should be sealed and disposed of appropriately as described by your doctor. Figure B: press (do not rub) with gauze or cotton ball