FLUXUM 3.200 U.I. Injectable solution

Зміст інструкції

1. FLUXUM 3.200 UI AXA injectable solution in pre-filled syringe, 4.250 UI AXA injectable solution in pre-filled syringe, 6.400 UI AXA injectable solution in pre-filled syringe, 8.500 UI AXA injectable solution in pre-filled syringe, 12.800 UI AXA injectable solution in pre-filled syringe
   1. What is Fluxum and what is it used for
   2. What you need to know before using Fluxum
   3. How to use Fluxum
   4. Possible side effects
   5. How to store Fluxum
   6. Contents of the pack and other information

FLUXUM 3.200 UI AXA injectable solution in pre-filled syringe, 4.250 UI AXA injectable solution in pre-filled syringe, 6.400 UI AXA injectable solution in pre-filled syringe, 8.500 UI AXA injectable solution in pre-filled syringe, 12.800 UI AXA injectable solution in pre-filled syringe

Parnaparina sodica
Read this leaflet carefully before you use 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. 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 or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Fluxum and what is it used for

Fluxum contains the active ingredient parnaparina sodium. Parnaparina sodium is a substance that belongs to the
class of anticoagulants, medicines used to treat blood clots in blood vessels and prevent their
formation.
Fluxum is used:

• to prevent the formation of blood clots in blood vessels (deep vein thrombosis) in patients undergoing general and orthopedic surgery and in patients at higher risk of developing deep vein thrombosis;
• to treat patients who have blood clots in blood vessels (deep vein thrombosis).

2. What you need to know before using Fluxum

DO NOT use Fluxum

• if you are allergic to parnaparina sodium or other low molecular weight heparins or to heparin or to substances of porcine origin or to any of the other components of this medicine (listed in section 6);
• if you are to undergo local or regional anesthesia for a surgical procedure and heparin is not administered for prevention;
• if you have had thrombocytopenia (low number of platelets in the blood) due to the administration of Fluxum (see also "Warnings and precautions");
• if you have problems with blood coagulation;
• if you suffer from any condition that leads to excessive bleeding, e.g. peptic ulcer, eye diseases called retinopathies, hemorrhagic syndrome;
• if you suffer from a condition known as acute infective endocarditis (inflammation of the membrane lining the heart and heart valves caused by an infection), unless it involves a prosthetic valve;
• if you have or have had bleeding in the blood vessels of the brain;
• if you have or have had a dilation of a vessel in the brain (cerebral aneurysm);
• if you have high blood pressure that is difficult to control (hypertension);
• if you have severe kidney and pancreas diseases, very high blood pressure, severe brain trauma (cranioencephalic trauma) in the post-operative period;
• if you are taking other medicines against the formation of blood clots (vitamin K antagonists), medicines that reduce platelet aggregation in the blood (antiplatelet agents) such as ticlopidine, salicylates or NSAIDs, dipyridamole, sulfinpyrazone.

Warnings and precautions
Talk to your doctor or pharmacist before using Fluxum.
Fluxum must not be administered intramuscularly.
Take special care with Fluxum

• if you suffer from thrombocytopenia due to heparin, a condition in which the number of clotting cells (platelets) decreases and bruises and bleeding appear easily. Thrombocytopenia is a known complication of heparin therapy and can occur 4 to 10 days after the start of treatment, but also earlier in patients who have previously had thrombocytopenia due to heparin. A mild form of thrombocytopenia may develop, which may remain stable or regress even if treatment is continued. In some cases, however, a more severe form of thrombocytopenia may occur, which can lead to the formation of new blood clots with serious complications, such as skin cell death (skin necrosis), blockage of an artery in the limbs or lungs, heart attack, stroke and sometimes death. In these cases, your doctor will assess whether to stop heparin therapy and administer a different anticoagulant. Your doctor will prescribe frequent blood tests to assess the number of platelets: before treatment and subsequently twice a week for the first month in case of prolonged administrations.
• if you are to undergo a surgical procedure (spinal or epidural anesthesia, epidural analgesia or lumbar puncture) inform your doctor that you are using Fluxum. In particular:
• if you are an elderly patient
• if you have problems with blood coagulation
• if you are using anti-inflammatory, antiplatelet and anticoagulant medicines (see section “Other medicines and Fluxum”)
• if you have had trauma or repeated spinal punctures.
• if you suffer from conditions that can easily cause bleeding and in particular if you have:
• a low number of platelets in the blood (thrombocytopenia) and platelet alterations
• a severe liver disease (hepatic insufficiency)
• a severe kidney disease (renal insufficiency)
• high blood pressure that is difficult to control
• eye diseases due to high blood pressure or diabetes (hypertensive or diabetic retinopathy)
• recently undergone surgery and are using high doses of Fluxum
• other conditions with a high risk of bleeding.
• if laboratory tests have shown a high level of potassium in your blood, because heparin can block the release of a hormone called aldosterone causing an increase in potassium levels in

the blood. This occurs particularly in patients with diabetes, kidney diseases (chronic renal insufficiency), excessive production of metabolic acids (metabolic acidosis), who already have high levels of potassium in the blood or who are taking medicines that reduce the elimination of potassium with the urine (potassium-sparing diuretics).
The risk of an increase in potassium levels increases based on the duration of therapy, but is generally temporary.
If you are a risk patient, your doctor will prescribe a check of potassium levels in the blood before starting therapy with heparin. In case of treatment lasting more than 7 days, your doctor will have you undergo regular checks.

• if you suffer from liver diseases (hepatic insufficiency)
• if you suffer from kidney diseases (renal insufficiency)
• if you have high blood pressure
• if you have had a stomach ulcer or other lesions that could bleed in the past
• if you suffer from eye problems due to vascular causes (vascular diseases of the chorio retina)
• if you have recently undergone brain or spinal cord surgery.

Interchangeability with other anticoagulants
Do not replace parnaparina sodium with other medicines with similar action (unfractionated heparins, other low molecular weight heparins or with synthetic origin molecules), as these medicines are different from each other, even in terms of efficacy and safety. Each of these medicines has its own specific instructions and conditions for use, therefore it is recommended not to switch from one brand to another during treatment.

Other medicines and Fluxum
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicine.
Tell your doctor if you are using:

• medicines that act on the processes of blood coagulation (hemostatic function) because they can increase the risk of bleeding. For example
• medicines that inhibit platelet function and glycoprotein IIb/IIIa receptor antagonists
• non-steroidal anti-inflammatory drugs (NSAIDs)
• medicines that reduce blood clotting time (anticoagulants: vitamin K antagonists) taken orally
• medicines used to dissolve blood clots in blood vessels (thrombolytics)
• dextran (medicine used, for example, to increase blood volume or to reduce blood coagulation)
• non-steroidal anti-inflammatory drugs (NSAIDs) or high doses of acetylsalicylic acid (ASA), especially if you suffer from kidney diseases (renal insufficiency) as these drugs reduce urine production;
• medicines for heart problems, for example
• nitroglycerin
• sulfinpyrazone
• ethacrynate
• digitalis and other digitalis
• antibiotics such as tetracyclines and penicillin (when administered by intravenous injection or taken at high doses);
• medicines to lower uric acid, for example probenecid;
• anti-cancer medicines (cytostatic agents);
• medicines for allergies (antihistamines);
• medicines for malaria (quinine);
• phenothiazines (psychotropic drugs);
• ascorbic acid (vitamin C);
• tobacco.

You should not take the following medicines in conjunction with Fluxum unless under strict medical supervision, as concomitant administration may increase the risk of bleeding:

• acetylsalicylic acid and other salicylates. Use other medicines to reduce pain and lower fever;
• non-steroidal anti-inflammatory drugs (NSAIDs);
• medicines that reduce platelet aggregation in the blood, for example
• ticlopidine
• clopidogrel
• dipyridamole
• sulfinpyrazone
• medicines that reduce blood coagulation (anticoagulants) taken orally;
• corticosteroids (hormonal medicines e.g. cortisone), if used at high doses or for a period of more than ten days;
• dextran (when used for injection, for example, to increase blood volume or to reduce blood coagulation).

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Studies in animals have not shown any adverse effects on normal fetal development or toxic effects on the embryo. However, there is no conclusive data on the passage of Fluxum through the placenta and excretion in breast milk. Fluxum can be used during pregnancy and/or breastfeeding according to your doctor's advice only if absolutely necessary, as the risk of harmful effects to the fetus or infant cannot be excluded.

Driving and using machines
Fluxum does not impair the ability to drive vehicles or use machines.
Clinical use of Fluxum even for many months has not shown any effects on the state of alertness.

Fluxum contains sodium
This medicine contains less than 1 mmol (23mg) of sodium per pre-filled syringe, i.e. it is essentially ‘sodium-free’.

3. How to use Fluxum

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have any doubts
consult your doctor or pharmacist.
Fluxum must be administered subcutaneously (subcutaneous use).

Dosage
The recommended dose to prevent the formation of blood clots in blood vessels (deep vein thrombosis) is:

• In general surgery: one subcutaneous injection of 0.3 ml (3,200 aXa IU) 2 hours before surgery. Subsequently every 24 hours for at least 7 days. Blood tests are not required.
• In orthopedic surgery: one subcutaneous injection of 0.4 ml (4,250 aXa IU) 12 hours before and 12 hours after surgery, followed by one injection per day in the days following the operation. The duration of treatment should be at least 10 days.
• In patients at higher risk of developing deep vein thrombosis: one subcutaneous injection of 0.4 ml (4,250 aXa IU) per day. The duration of treatment should be at least 10 days.

The recommended dose to treat blood clots in blood vessels (deep vein thrombosis) is:

• Two injections per day subcutaneously of 0.6 ml (6,400 aXa IU). The duration of treatment should be at least 7-10 days. 3-5 days before this therapy, you may be given therapy with Fluxum 12,800 aXa IU intravenously in slow infusion.

After the acute phase, therapy can be continued for another 10-20 days with one subcutaneous injection
of 0.8 ml (8,500 aXa IU) per day or 0.6 ml (6,400 aXa IU) per day or with 0.4 ml (4,250 aXa IU
per day.
If there are no contraindications, your doctor will prescribe oral anticoagulant therapy to start
as soon as possible.
Treatment with Fluxum should not be interrupted before reaching the required INR (International
Normalization Ratio, a value that measures the blood's ability to coagulate).

How to inject Fluxum
Your doctor or other qualified personnel will show you how to perform the injection correctly.
The injection must be given into the subcutaneous tissue (under the skin) in one of the following areas,
alternating between the right and left sides:

• abdominal wall (on the stomach at belt level), anterolateral or posterolateral, towards the flank;
• upper and outer part of the buttocks, towards the flank. The needle must be inserted completely, vertically and not obliquely, into the thickness of the skin fold created by pinching the skin between the thumb and index finger. The skin fold must be maintained throughout the duration of the injection. The presence of an air bubble in the syringe is normal and should not be removed before use.

Prefilled syringes with safety system
The prefilled syringes are equipped with a safety system to prevent accidental needle sticks after
the injection. At the end of the plunger stroke, at the end of administration, the safety mechanism is activated
automatically covering the needle with a protective cap.

If you use more Fluxum than you should
In case of ingestion/accidental intake of an excessive dose of Fluxum, immediately inform your
doctor or go to the nearest hospital.
Overdosage is unlikely due to the particular packaging in which this medicine is presented.
However, if accidental overdose cases occur, effects related to anticoagulant activity (bleeding) may occur which normally do not occur at
therapeutic doses.

If you forget to use Fluxum
Do not use a double dose to make up for a missed dose.

If you stop using Fluxum
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.
Do not stop using Fluxum without talking to your doctor first, as the risk of developing a
blood clot may be higher if you stop treatment too soon.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects associated with Fluxum, classified according to how frequently they may occur,
are listed below:

Common (may affect up to 1 in 10 people)

• localized blood collection under the skin (hematoma) due to rupture of a blood vessel at the injection site
• bleeding (haemorrhage)
• irritation, pain and discomfort at the injection site

Uncommon (may affect up to 1 in 100 people)

• increase in certain liver enzymes (transaminases)

Rare (may affect up to 1 in 1,000 people)

• low number of platelets in the blood (thrombocytopenia), in some cases severe (see also section “Warnings and precautions”)
• minor bleeding, mainly due to pre-existing risk factors e.g. lesions with a tendency to bleed or medical treatments (see also section “Warnings and precautions”)
• skin inflammation (dermatitis), skin redness (erythema), itching, reddish-brown skin spots (purpura), skin eruption or rash and urticaria
• skin redness (erythema with plaques), reddish-brown skin spots (purpura), death of skin cells (skin necrosis) at the injection site

Very rare (may affect up to 1 in 10,000 people)

• severe allergic reactions (anaphylactic reactions or similar to anaphylaxis)
• blood collection due to rupture of a blood vessel at the level of the spinal cord or meninges (spinal or epidural hematoma), associated with the preventive use of heparin during spinal, epidural or lumbar puncture anesthesia (see also section “Warnings and precautions”)

Not known (frequency cannot be estimated from available data)

• reduction in the number of red blood cells (anemia)
• decreased level of consciousness
• formation of blood clots in blood vessels (deep vein thrombosis)
• hot flushes
• difficulty breathing (dyspnea)
• nosebleed (epistaxis)
• swelling of the pharynx (pharyngeal edema)
• bleeding from the pleura (membrane lining the lungs) (pleural haemorrhage)
• abdominal pain
• diarrhoea
• swelling of the lips (lip edema)
• dark, bloody stools (melena)
• nausea
• yellowing of the skin, mucous membranes and eyes (jaundice)
• inflammation of the gallbladder and bile ducts associated with jaundice (cholestatic hepatitis)
• skin eruption with small spots and raised areas (maculopapular rash)
• generalized itching
• joint pain (arthralgia)
• muscle pain (myalgia)
• non-menstrual uterine bleeding (metrorrhagia)
• weakness (asthenia), fatigue

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 at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Fluxum

Keep this medicine out of the sight and reach of children.
Do not store at a temperature above 30°C.
Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the last day of that month.
Do not use this medicine if the packaging has been opened or damaged.
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 Fluxum contains

• The active ingredient is parnaparina sodium.
• The other component is water for injections.

Each pre-filled syringe of 0.3 ml contains parnaparina sodium 3,200 IU aXa
Each pre-filled syringe of 0.4 ml contains parnaparina sodium 4,250 IU aXa
Each pre-filled syringe of 0.6 ml contains parnaparina sodium 6,400 IU aXa
Each pre-filled syringe of 0.8 ml contains parnaparina sodium 8,500 IU aXa
Each pre-filled syringe of 1 ml contains parnaparina sodium 12,800 IU aXa

Description of the appearance of Fluxum and contents of the pack
Fluxum is presented as an injectable solution for subcutaneous administration.
Fluxum is supplied in a cardboard box containing pre-filled syringes with or without a safety system
inserted in a polystyrene tray.
Fluxum is available in the following pack sizes:
Pack of 6 pre-filled 0.3 ml syringes
Pack of 6 pre-filled 0.4 ml syringes
Pack of 6 pre-filled 0.6 ml syringes
Pack of 2 pre-filled 0.8 ml syringes
Pack of 6 pre-filled 0.8 ml syringes
Pack of 2 pre-filled 1 ml syringes

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Alfasigma S.p.A. – Via Ragazzi del ‘99, n. 5 - 40133 Bologna (BO)
Manufacturer:
Alfasigma S.p.A. – Via E. Fermi, n. 1 – 65020 Alanno (PE)