HEPARIN SODIUM

9% sodium chloride or by intermittent intravenous injection, or by subcutaneous injection. The intravenous injection volume of heparin injection should not exceed 15 mL. As the effects of heparin are short-lived, administration by intravenous infusion or subcutaneous injection is preferable to intermittent intravenous injections.

Posology 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.

Paediatric population:

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 subcutaneously, or 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.

The following adverse reactions have been observed and reported during treatment with Heparin Sodium with the following frequencies: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1, 000); very rare (<1/10, 000), not known (cannot be estimated from available data).

Adverse Drug Reactions System Organ Class (SOC) MedDRA Preferred Term Frequency Haemorrhage Not known Vascular disorders Epistaxis Not known Contusion Not known Blood and lymphatic system disorders Thrombocytopenia Not known Renal and urinary disorders Haematuria Not known Adrenal insufficiency Not known Endocrine disorders Hypoaldosteronism Not known Skin and subcutaneous tissue disorders Alopecia Not known System Organ Class (SOC) MedDRA Preferred Term Frequency Skin necrosis Not known Musculoskeletal, connective tissue and bone disorders Osteoporosis Not known Immune system disorders Hypersensitivity Not known Rebound hyperlipidaemia Not known Metabolism and nutrition disorders Hyperkalaemia Hypokalaemia Not known Reproductive system and breast disorders Priapism Not known General disorders and administration site conditions Injection site reaction Not known Investigations Alanine aminotransferase increased; Aspartate aminotransferase increased Not known Hypersensitivity reactions to heparin are rare.

They include urticaria, conjunctivitis, rhinitis, asthma, cyanosis, tachypnoea, feeling of oppression, fever, chills, angioneurotic oedema and anaphylactic shock. Erythematous nodules, or infiltrated and sometimes eczema-like plaques, at the site of subcutaneous injections are common, occurring 3 – 21 days after starting heparin treatment.

Haemorrhage:

Haemorrhage is the chief complication that may result from heparin therapy. An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug. It should be appreciated that gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion.

Heparin should be used with caution in patients with hypersensitivity to low molecular weight heparin. Care should be taken when heparin is administered to patients with increased risk of bleeding complications, hypertension, renal or hepatic insufficiency.

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). Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, 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 hyperkalaemia 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 monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days.

5). In patients undergoing peri-dural or spinal anaesthesia or spinal puncture, the prophylactic use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis. The risk is increased by the use of a peri-dural or spinal catheter for anaesthesia, by the concomitant use of drugs affecting haemostasis such as non-steroidal anti-inflammatory drugs, platelet inhibitors or anticoagulants and by traumatic or repeated puncture.

In decision making on the interval between the last administration of heparin at prophylactic doses and the placement or removal of a peri-dural or spinal catheter, the product characteristics and the patient profile should be taken into account.

Subsequent dose should not take place before at least four hours have elapsed. Re-administration should be delayed until the surgical procedure is completed. Should a physician decide to administer anti-coagulation in the context of peridural or spinal anaesthesia, extreme vigilance and frequent monitoring must be exercised to detect any signs and symptoms of neurologic impairment, such as back pain, sensory and motor deficits and bowel or bladder dysfunction.

1. Current (or history of) heparin-induced thrombocytopenia. Generalised or local haemorrhagic tendency. An epidural anaesthesia during birth in pregnant women treated with heparin is contraindicated. Regional anaesthesia in elective surgical procedures is contra-indicated because the use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis.

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.