PROTAMINE injectable

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    Last updated: August 2022


    Prescription under medical supervision


    Therapeutic action

    • Neutralisation of the anticoagulant action of unfractionated heparin
    • Partial neutralisation of the anticoagulant action of low molecular weight heparin


    • Haemorrhagic syndromes resulting from accidental heparin overdosage

    Forms and strengths, route of administration

    • 50 mg protamine sulfate in 5 ml ampoule (10 mg/ml) for slow IV injection

    Concentration may be expressed in antiheparin units (AHU): 1000 AHU = 10 mg.


    Depends on the amount of heparin to be neutralised.


    Heparin overdosage

    • If administered between 0 and 30 minutes after the heparin injection, 1 mg of protamine sulfate (100 AHU) neutralises 100 units of heparin.
    • If more than 30 minutes have elapsed since the heparin injection, the dose of protamine to be given should be one half the dose of heparin injected.
    • Do not administer more than 50 mg per dose


    Enoxaparin overdosage

    Time since last enoxaparin dose

    Protamine dose

    < 8 hours

    1 mg per 1 mg enoxaparin

    > 8 hours and < 12 hours

    0.5 mg per 1 mg enoxaparin

    > 12 hours

    May not be required


    • Do not administer more than 50 mg per dose.


    • According to clinical response. Monitor coagulation parameters.

    Contra-indications, adverse effects, precautions

    • May cause: hypotension, bradycardia and dyspnoea; allergic reactions, notably in diabetics treated by protamine-insulin.
    • If excessive doses are used, haemorrhage may persist or reappear, as protamine sulfate itself has some anticoagulant activity.
    • Administer by very slow IV (over 10 minutes) in order to reduce risks of hypotension and bradycardia.
    • Pregnancy: no contra-indication
    • Breast-feeding: no contra-indication


    • Anticoagulant effect of protamine may vary according to the origin of the heparin: follow manufacturer's recommendations.
    • Protamine sulfate may be used to neutralize the effect of heparin before surgery.


    –  To be kept refrigerated (2 °C to 8 °C)