Document: leaflet MAH GENERIC_PL 29831-0110 change

• leaflet MAH BRAND_PL 29831-0110
• leaflet MAH GENERIC_PL 29831-0110

---

PACKAGE LEAFLET: INFORMATION FOR THE USER

HEPARIN SODIUM 5,000 I.U./ml solution for injection or concentrate for solution for infusion HEPARIN SODIUM 25,000 I.U./ml solution for injection or concentrate for solution for infusion Contains Preservative

Read all of this leaflet carefully before you start taking this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, please ask your doctor or nurse.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

The name of your medicine is either heparin sodium 5,000 I.U./ml or heparin sodium 25,000 I.U./ml solution for injection or concentrate for solution for infusion. In the rest of this leaflet it is called heparin injection.

In this leaflet:

1.    What heparin injection is and what it is used for

2.    Before you are given heparin injection

3.    How heparin injection is given

4.    Possible side effects

5.    How to store heparin injection

6.    Further information

1. WHAT HEPARIN INJECTION IS AND WHAT IT IS USED FOR

Heparin belongs to a group of drugs that are called anticoagulants.

These help to stop blood clotting. Heparin injection 5,000 I.U./ml or

25,000 I.U./ml is used in conditions where blood vessels may become

blocked by blood clots. It is therefore used to treat and prevent:

•    blood clots in leg veins (deep vein thrombosis)

•    blood clots in the lung (pulmonary embolism) as well as for:

•    the treatment of chest pains resulting from disease of the heart arteries (unstable angina pectoris)

•    the treatment of severe blockages affecting arteries in the legs (acute peripheral arterial occlusion)

•    the prevention of blood clots in the heart following a heart attack (mural thrombosis).

It is also used during heart and lung operations and during kidney

dialysis.

2. BEFORE YOU ARE GIVEN HEPARIN INJECTION

Heparin injection should not be given if you:

•    are allergic to heparin or any of the other ingredients in your medicine, (see 'What heparin injection contains'section 6 and 'Important information about some of the ingredients of heparin injection' below)

•    drink large amounts of alcohol

•    are currently bleeding from anywhere in the body, (apart from your normal period which does not stop you being given heparin injection)

•    have haemophilia (a genetic disorder which may cause you to bleed excessively) or any other bleeding problem

•    have or have ever had thrombocytopenia (a serious blood disorder which prevents blood from clotting properly)

•    bruise easily (fragile capillaries) or have lots of purple spots that look like bruises (purpura)

•    have very high blood pressure

•    are suffering from tuberculosis (TB)

•    have had severe skin problems resulting from previous heparin treatment

•    are about to have surgery of the brain, spine or eye, a lumbar puncture or local anaesthetic nerve block, or some other procedure where bleeding could be a problem

•    have recently had an operation

•    suffer from severe liver problems which can lead to bleeding into the oesophagus (gullet)

•    have bleeding into the brain.

Heparin injection must not be given to premature or

newborn babies.

Speak to your doctor before heparin injection is given if you:

•    are over 60 years of age

•    have any condition which makes you likely to bleed more easily (for example a stomach ulcer, hiatus hernia, inflammation of the heart, problems in the back of your eye, haemorrhoids (piles),

a stroke, cancer or threatened miscarriage), If you are unsure, ask your doctor or nurse.

•    suffer from diabetes

•    suffer from excess acid or high levels of potassium in your blood or are taking a medicine that may increase the potassium level in your blood (e.g. amiloride, triamterene, eplerenone or spironolactone). If any of these apply you may need to have a blood test before the start of your heparin treatment. If you are unsure, ask your doctor or nurse

•    have kidney or liver disease. Your doctor may decide that a lower dose is necessary

•    suffer from allergies or have previously had an allergic reaction to low molecular weight (LMW) heparin. A small test dose of heparin sodium injection may be given first.

Your doctor will check your blood if you receive treatment for longer

than five days and may do other blood tests if you have major

surgery.

Your doctor will take particular care if:

•    the patient is an infant or child under three years old

•    you have an epidural or an anaesthetic given into the spine.

Taking other medicines

It is very important that you inform your doctor if you are taking, or have recently taken, any other medicines, including those medicines obtained without a prescription, as some medicines may affect the way heparin injection works. Taking some medicines at the same time as heparin may mean you may be likely to bleed more.

In particular, tell your doctor if you are taking any of the following:

•    aspirin or other non-steroidal anti-inflammatory drugs (e.g diclofenac or ibuprofen)

•    dextran solutions (used to treat shock)

•    medicines which may interfere with the proper clotting of the blood (e.g. dipyridamole, epoprostenol, clopidogrel or streptokinase)

•    cephalosporins, used to treat infections

•    medicines called ACE inhibitors used for high blood pressure and heart failure (e.g. captopril enalapril, lisinopril or ramapril)

•    medicines that may increase the potassium level in your blood (e.g. amiloride, triamterene, eplerenone or spironolactone

•    glyceryl trinitrate given into a vein (for coronary heart disease)

•    aminoglycoside antibiotics (e.g. gentamicin, amikacin, neomycin or tobramycin)

•    probenecid, used in the treatment of gout

If you need one of the above medicines your doctor may decide to alter the dose of heparin injection or the other medication. If you have any doubts about whether this medicine should be administered then discuss things more fully with your doctor or nurse before it is given.

Tobacco smoke can also interfere with the working of heparin injection. You should inform your doctor if you smoke.

The presence of heparin in the blood can affect the results of some blood tests such as thyroid tests and the levels of calcium or some antibiotics (e.g. gentamicin) in the blood.

Important information about the ingredients benzyl alcohol and methyl parahydroxybenzoate

The benzyl alcohol in heparin injection may cause toxic reactions and allergic reactions in infants and children up to three years old.

The methyl parahydroxybenzoate in heparin injection may cause allergic reactions (possibly delayed) and exceptionally bronchospasm Pregnancy and breast-feeding You should let your doctor or nurse know before you are given heparin injection if you are pregnant or wish to become pregnant.

If you are being given heparin injection bleeding may be a problem during pregnancy or after delivery. Your bones may get thinner if you receive heparin for a long time during pregnancy.

Ask your doctor or nurse for advice if you wish to breast-feed

Driving and using machines

Heparin injection has not been reported to affect ability to drive or operate machines._

3. HOW HEPARIN INJECTION SHOULD BE GIVEN

Your doctor or nurse will inject your dose of heparin into a vein either all at once or over a longer period of time (usually via a drip). Alternatively they may inject your heparin underneath your skin.

The amount injected all at once into a vein should not be greater than 15ml.

You may need to have blood tests if you are receiving higher doses of heparin or if you are pregnant to check on the effects of your heparin treatment.

Heparin injection must not be given to premature or newborn babies.

You may require a lower dose if you have kidney or liver disease.

To PREVENT blood clots in leg veins (deep vein thrombosis) and blood clots in the lung (pulmonary embolism)

Adults

The usual dose of heparin injection in adults is 5,000 units injected under the skin 2 hours before your operation, followed by 5,000 units injected under the skin every 8-12 hours, for 7-10 days or until you are fully able to move about.

Pregnancy

During pregnancy the dosage is 5,000-10,000 units injected under the skin every 12 hours. The dose may be adjusted according to your blood tests.

Elderly

Lower doses may be used in the elderly. You may need to have blood tests if you are elderly, to check on the effects of your heparin treatment.

Children

No specific doses are recommended.

To TREAT blood clots in leg veins (deep vein thrombosis) and blood clots in the lung (pulmonary embolism).

Adults

The usual dose in adults is 5,000 units injected into a vein. This is followed by:

•    1,000-2,000 units/hour injected slowly into a vein

or

•    10,000-20,000 units 12 hourly injected under the skin

or

•    5,000-10,000 units 4 hourly injected all at once into a vein Elderly

Lower doses may be used in the elderly

105013/4

--------------------------2^.

1.    NAME OF THE MEDICINAL PRODUCT

Heparin sodium 5,000 I.U./ml solution for injection or concentrate for solution for infusion

Heparin sodium 25,000 I.U./ml solution for injection or concentrate for solution for infusion

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Heparin sodium 5,000 I.U./ml - Heparin sodium 5,000 I.U./ml (25,000 I.U. in 5ml)

Heparin sodium 25,000 I.U./ml - Heparin sodium 25,000 I.U./ml (125,000 I.U. in 5ml)

For a full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Solution for injection or concentrate for solution for infusion A colourless or straw-coloured liquid, free from turbidity and from matter that deposits on standing.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Prophylaxis of deep vein thrombosis and pulmonary embolism

Treatment of deep vein thrombosis, pulmonary embolism, unstable angina pectoris and acute peripheral arterial occlusion.

Prophylaxis of mural thrombosis following myocardial infarction.

In extracorporeal circulation and haemodialysis.

4.2    Posology and method of administration Route of administration

By continuous intravenous infusion in 5% glucose or 0.9% sodium chloride or by intermittent intravenous injection, or by subcutaneous injection.

The intravenous injection volume of heparin injection should not exceed 15ml.

As the effects of heparin are short-lived, administration by intravenous infusion or subcutaneous injection is preferable to intermittent intravenous injections.

Recommended dosage

Prophylaxis of deep vein thrombosis and pulmonary embolism:

Adults:

2 hours pre-operatively:    5,000 units subcutaneously

Followed by:    5,000 units subcutaneously every

8-12 hours, for 7-10 days or until the patient is fully ambulant.

No laboratory monitoring should be necessary during low dose heparin prophylaxis. If monitoring is considered desirable, anti-Xa assays should be used as the activated partial thromboplastin time (APTT) is not significantly prolonged.

During pregnancy:    5,000 - 10,000 units every 12 hours,

subcutaneously, adjusted according to APTT or anti-Xa assay.

Elderly:

Dosage reduction and monitoring of APTT may be advisable.

Children:

No dosage recommendations.

Treatment of deep vein thrombosis and pulmonary embolism:

Adults:

Loading dose:    5,000 units intravenously (10,000 units

may be required in severe pulmonary embolism)

Maintenance:    1,000-2,000 units/hour by intravenous

infusion, or 10,000-20,000 units 12 hourly subcutaneously, or 5,000-10,000 units 4-hourly by intravenous injection.

Elderly:

Dosage reduction may be advisable.

Children and small adults:

Loading dose:    50 units/kg intravenously

Maintenance:    15-25 units/kg/hour by intravenous

infusion,

or 250 units/kg 12 hourly subcutaneouslyor 100 units/kg 4-hourly by intravenous injection

Treatment of unstable angina pectoris and acute peripheral arterial occlusion:

Adults:

Loading dose:    5,000 units intravenously

Maintenance:    1,000-2,000 units/hour by intravenous

infusion, or 5,000-10,000 units 4-hourly by intravenous injection.

Elderly:

Dosage reduction may be advisable.

Children and small adults:

Loading dose:    50 units/kg intravenously

Maintenance:    15-25 units/kg/hour by intravenous

infusion, or 100 units/kg 4-hourly by intravenous injection

Daily laboratory monitoring (ideally at the same time each day, starting 4-6 hours after initiation of treatment) is essential during full-dose heparin treatment, with adjustment of dosage to maintain an APTT value 1.5-2.5 x midpoint of normal range or control value.

Prophylaxis of mural thrombosis following myocardial infarction

In extracorporeal circulation and haemodialysis Adults:

Cardiopulmonary bypass:    Initially 300 units/kg intravenously,

adjusted thereafter to maintain the activated clotting time (ACT) in the range 400-500 seconds.

Haemodialysis and

haemofiltration:    Initially 1,000-5,000 units,

Maintenance:    1,000-2,000 units/hour, adjusted to

maintain clotting time >40 minutes.

Heparin resistance

Patients with altered heparin responsiveness or heparin resistance may require disproportionately higher doses of heparin to achieve the desired effect. Also refer to section 4.4, Special warnings and precautions for use.

4.3 Contraindications

Known hypersensitivity to heparin or any of the other ingredients.

Must not be given to premature babies or neonates (contains benzyl alcohol).

Patients who consume large amounts of alcohol, who are sensitive to the drug, who are actively bleeding or who have haemophilia or other bleeding disorders, severe liver disease (including oesophageal varices), purpura, severe hypertension, active tuberculosis or increased capillary permeability.

Patients with present or previous thrombocytopenia. The rare occurrence of skin necrosis in patients receiving heparin contra-indicates the further use of heparin either by subcutaneous or intravenous routes because of the risk of thrombocytopenia. Because of the special hazard of post-operative haemorrhage heparin is contra-indicated during surgery of the brain, spinal cord and eye, in procedures at sites where there is a risk of bleeding, in patients that have had recent surgery, and in patients undergoing lumbar puncture or regional anaesthetic block.

The relative risks and benefits of heparin should be carefully assessed in patients with a bleeding tendency or those patients with an actual or potential bleeding site eg. hiatus hernia, peptic ulcer, neoplasm, bacterial endocarditis, retinopathy, bleeding haemorrhoids, suspected intracranial haemorrhage, cerebral thrombosis or threatened abortion.

Menstruation is not a contra-indication.

4.4Special warnings and precautions for use

Platelet counts should be measured in patients receiving heparin treatment for longer than 5 days and the treatment should be stopped immediately in those who develop thrombocytopenia.

In patients with advanced renal or hepatic disease, a reduction in dosage may be necessary. The risk of bleeding is increased with severe renal impairment and in the elderly (particularly elderly women).

Although heparin hypersensitivity is rare, it is advisable to give a trial dose of 1,000 I.U. in patients with a history of allergy. Caution should be exercised in patients with known hypersensitivity to low molecular weight heparins.

Heparin injection contains benzyl alcohol (10mg/ml) and methyl parahydroxybenzoate as preservatives. Caution should be used if prescribing Heparin injection to susceptible patients. Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in infants and children up to three years old. Methyl parahydroxybenzoate may cause allergic reactions (possibly delayed) and, exceptionally, bronchospasm.

In most patients, the recommended low-dose regimen produces no alteration in clotting time. However, patients show an individual response to heparin, and it is therefore essential that the effect of therapy on coagulation time should be monitored in patients undergoing major surgery.

Caution is recommended in spinal or epidural anaesthesia (risk of spinal haematoma).

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium, or taking potassium sparing drugs. The risk of hyperkalemia appears to increase with duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and in all patients treated for more than 7 days.

Heparin resistance

There is considerable variation in individual anticoagulant responses to heparin.

Heparin resistance, defined as an inadequate response to heparin at a standard dose for achieving a therapeutic goal occurs in approximately 5 to 30% of patients.

Factors predisposing to the development of heparin resistance, include:

•    Antithrombin III activity less than 60% of normal (antithrombin III-dependent heparin resistance):

Reduced antithrombin III activity may be hereditary or more commonly, acquired (secondary to preoperative heparin therapy in the main, chronic liver disease, nephrotic syndrome, cardiopulmonary bypass, low grade disseminated intravascular coagulation or drug induced, e.g. by aprotinin, oestrogen or possibly nitroglycerin)

•    Patients with normal or supranormal antithrombin III levels (antithrombin III- independent heparin resistance)

•    Thromboembolic disorders

•    Increased heparin clearance

•    Elevated levels of heparin binding proteins, factor VIII, von Willebrand factor, fibrinogen, platelet factor 4 or histidine-rich glycoprotein

•    Active infection (sepsis or endocarditis)

•    Preoperative intra-aortic balloon counterpulsation

•    Thrombocytopenia