Slight haemorrhage due to overdosage can usually be treated by withdrawing the drug. Severe bleeding may be reduced by the administration of protamine sulphate. Protamine sulphate should be administered intravenously. To avoid circulatory side effects, the injection should be given slowly at a rate of 5 mL over a period of about 10 minutes. Not more than 50 mg should be given at any one time. The dose of protamine sulphate required is governed by the amount of heparin that has to be neutralised; approximately 1 mg of protamine sulphate neutralises 110 units of heparin (mucous) that has been injected in the previous 15 minutes. Since heparin is being continuously excreted, the dose should be reduced as more time elapses after the heparin injection. Ideally, the dose of protamine sulphate required should be accurately determined by titration methods as the antagonist itself, in gross excess, acts as an anticoagulant.
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