Heparin Leo Overdosage

Bleeding may be a complication of therapy.
Slight epistaxis, occasional red cells in the urine, and bruising are signs of overdosage.
Slight haemorrhage due to overdosage can usually be treated by withdrawing the drug. Severe bleeding may be reduced by the administration of protamine sulphate.
The effect of heparin can be reversed immediately by intravenous administration of 1% protamine sulphate solution. The injection should be given very slowly (over one to three minutes). The quantity of protamine required for neutralization falls rapidly with the lapse of time after the administration of heparin. If given within 15 minutes of the heparin injection, 10 mg of protamine will neutralize 1,000 i.u. of heparin, while 30 minutes after the heparin injection of 1,000 i.u., only 5 mg of protamine sulphate is needed. If more time has elapsed after the administration of heparin, the dose of protamine sulphate required for neutralization should be determined accurately by titrating with the patient's plasma.
It is important to avoid overdosage of protamine sulphate because protamine itself has anticoagulant properties. The dosage should not exceed the equivalent of 50 mg protamine sulphate in any ten-minute period. Intravenous injection of protamine may cause a sudden fall in blood pressure, bradycardia, dyspnoea, and transitory flushing, but these may be avoided or diminished by slow administration.