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Protamine (Protamine Sulfate) - Drug Interactions, Contraindications, Overdosage, etc



PROTAMINE drug label information in our database does not contain a dedicated section on drug interactions. Please check subsections of WARNINGS AND PRECAUTIONS as well as other sources.


Signs and Symptoms

Overdose of protamine sulfate may cause bleeding.  Protamine has a weak anticoagulant effect due to an interaction with platelets and with many proteins including fibrinogen.  This effect should be distinguished from the rebound anticoagulation that may occur 30 minutes to 18 hours following the reversal of heparin with protamine.

Rapid administration of protamine is more likely to result in bradycardia, dyspnea, a sensation of warmth, flushing, and severe hypotension.  Hypertension has also occurred.

The median lethal dose of protamine sulfate is 50 mg/kg in mice.  Serum concentrations of protamine sulfate are not clinically useful.  Information is not available on the amount of drug in a single dose that is associated with overdosage or is likely to be life-threatening.


To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center.  Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR) .  In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in your patient.

Replace blood loss with blood transfusions or fresh frozen plasma. 

If the patient is hypotensive, consider fluids, epinephrine, dobutamine or dopamine.


Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug.

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