Protamine sulfate is a strongly basic, low molecular weight protein derived from the sperm of salmon and certain other fish species. It is a specific antidote to heparin, forming a stable, inactive complex through an acid-base interaction, thereby neutralizing the anticoagulant effect of both unfractionated heparin (UFH) and low molecular weight heparins (LMWHs). Its use is critical in cardiac surgery, vascular procedures, and emergency reversal of heparin overdose.
Adult: Dose is based on the amount of heparin to be neutralized and the time since heparin administration. General guideline: 1 mg of protamine sulfate neutralizes approximately 100 USP units of heparin. If heparin was given within 30 minutes, use full calculated dose. If 30-60 minutes have passed, use 0.5-0.75 mg per 100 units heparin. If >2 hours, use 0.25-0.375 mg per 100 units heparin. A single dose should not exceed 50 mg. Administer SLOW IV over 10 minutes.
Note: For IV use only. Must be administered as a slow intravenous injection over at least 10 minutes. Rapid injection can cause severe hypotension, bradycardia, pulmonary hypertension, and anaphylactoid reactions. Must be administered in a setting with resuscitation equipment and drugs available. The 50mg vial is typically diluted in 5-10 mL of sterile water for injection or 5% dextrose.
Protamine sulfate is a strongly cationic (positively charged) protein that binds ionically to the strongly anionic (negatively charged) heparin molecule. This binding forms a stable, biologically inactive salt complex (1:1 ratio by weight), which precipitates the anticoagulant activity. This neutralizes the ability of heparin to activate antithrombin III, thereby rapidly restoring normal coagulation parameters.
Pregnancy: US FDA Category C. Animal reproduction studies not conducted. Should be used during pregnancy only if clearly needed, such as in life-threatening situations like cardiopulmonary bypass. Benefits may outweigh risks.
Driving: Not applicable. Administered in a controlled clinical setting.
| Insulin (especially NPH/Protamine-based) | Increased risk of hypersensitivity reactions to protamine. | Moderate |
| Antihypertensive drugs, Vasodilators | Additive hypotensive effect with rapid protamine infusion. | Moderate |
| Heparin | Protamine neutralizes heparin. This is the intended therapeutic interaction. | High (Therapeutic) |