Heparin antagonists, heparin effects wear off so rapidly that an antagonist is seldom required except after perfusion for open- heart surgery.

Protamine sulfate, which is strongly basic, acts as a heparin antagonist in vitro and in vivo by complexing with strongly acidic heparin to form a stable salt.

Following IV administration of an appropriate dose of protamine sulfate, neutralization of heparin occurs within 5 minutes. A median elimination half-life: 4.5-7.5 minutes

It is unwise to give more than 100mg over a short period unless there is certain knowledge of a large requirement. Patients with a history of allergy to fish may develop hypersensitivity reactions of protamine.

It is not known whether protamine sulfate can cause fetal harm when administered to pregnant women or can affect reproduction capacity. The drug should be used during pregnancy only when clearly needed.

It is not known whether protamine sulfate is distributed into human milk.

A sudden fall in blood pressure, bradycardia, dyspnea, transitory flushing, and feeling of warmth.

Protamine 1mg neutralized 100 IU of heparin. In heparin overdose: it can be given as a loading of 25-50 mg by slow IV injection, with the rest of calculated dose over 8-16 hrs.