Product Name: Heparin sodium Injection
Nombre del Producto: Heparina sódica solución Inyectable
Specification: 25000iu/5ml
Package: 10viales/box, 50viales/box
Standard: USP & BP & CP
Indication
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.
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 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.
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
Adults:
12,500 units 12 hourly subcutaneously for at least 10 days.
Elderly:
Dosage reduction may be advisable
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 1-5,000 units,
Maintenance: 1-2,000 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.
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.
Special 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
• Thrombocytosis
• Advanced age
• Plasma albumin concentration ≤ 35g/dl
• Relative hypovolaemia
Heparin resistance is also often encountered in acutely ill patients, in patients with malignancy and during pregnancy or the post-partum period.
Undesirable effects
Haemorrhage (see also Special Warnings and Precautions and Overdosage Information).
Adrenal insufficiency secondary to adrenal haemorrhage has been associated with heparin (rarely).
Thrombocytopenia has been observed occasionally (see also Special Precautions and Warnings). Two types of heparin-induced thrombocytopenia have been defined. Type I is frequent, mild (usually>50 x 109/L) and transient, occurring within 1-5 days of heparin administration. Type II is less frequent but often associated with severe thrombocytopenia (usually <50 x 109/L). It is immune-mediated and occurs after a week or more (earlier in patients previously exposed to heparin). It is associated with the production of a platelet-aggregating antibody and thromboembolic complications which may precede the onset of thrombocytopenia. Heparin should be discontinued immediately.
There is some evidence that prolonged dosing with heparin (ie. over many months) may cause alopecia and osteoporosis. Significant bone demineralisation has been reported in women taking more than 10,000 I.U. per day of heparin for at least 6 months.
Heparin products can cause hypoaldosteronism which may result in an increase in plasma potassium. Rarely, clinically significant hyperkalemia may occur particularly in patients with chronic renal failure and diabetes mellitus (see Warnings and Precautions).
Hypersensitivity reactions to heparin are rare. They include urticaria, conjunctivitis, rhinitis, asthma, cyanosis, tachypnoea, feeling of oppression, fever, chills, angioneurotic oedema and anaphylactic shock. In some instances the precipitating agent will prove to be the preservative rather than the heparin itself.
Local irritation and skin necrosis may occur but are rare. 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.
Priapism has been reported. Increased serum transaminase values may occur but usually resolve on discontinuation of heparin. Heparin administration is associated with release of lipoprotein lipase into the plasma; rebound hyperlipidaemia may follow heparin withdrawal.
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