protamine sulfate

Available forms
Available by prescription only
Injection: 10 mg/ml in 5-ml ampule, 25-ml ampule, 5-ml vial, 10-ml vial, 25-ml vial

Indications and dosages
 Heparin overdose. Adults and children: Dosage based on venous blood coagulation studies, usually 1 mg for each 90 units of heparin derived from lung tissue or 1 mg for each 115 units of heparin derived from intestinal mucosa. Give by slow I.V. injection over 1 to 3 minutes. Maximum dose is 50 mg in any 10-minute period.

Pharmacodynamics
Heparin antagonism: Has weak anticoagulant activity; however, when given in the presence of heparin, forms a salt that neutralizes anticoagulant effects of both drugs.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: No information available.
Metabolism: Fate of heparin-protamine complex unknown; appears to be partially degraded, with release of some heparin.
Excretion: Binding action lasts about 2 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously after cardiac surgery.

Interactions
None reported.

Adverse reactions
CV: hypotension, bradycardia, circulatory collapse, lassitude.
GI: nausea, vomiting.
Hematologic: shortens heparin-prolonged PTT.
Respiratory: dyspnea, pulmonary edema, acute pulmonary hypertension.
Other: transitory flushing, feeling of warmth, anaphylaxis, anaphylactoid reactions.

Effects on lab test results
None reported.

Overdose and treatment
Overdose may cause bleeding secondary to interaction with platelets and proteins including fibrinogen.
 Replace blood loss with blood transfusions or fresh frozen plasma. If hypotension occurs, consider treating with fluids, epinephrine, dobutamine, or dopamine.

Special considerations
• Check for possible fish allergy.
• Dosage is based on blood coagulation studies as well as on route of administration of heparin and time elapsed since heparin was administered.
• Don’t mix protamine with any other drug.
• Reconstitute powder by adding 5 ml sterile water to 50-mg vial (25 ml to 250-mg vial); discard unused solution.
• Slow I.V. administration (over 1 to 3 minutes) decreases adverse effects; have antishock equipment available.
• Watch for sudden decrease in blood pressure. Monitor patient continually, and check vital signs frequently.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy haven’t been established.

Patient education
• Advise patient that he may experience transitory flushing or feel warm after I.V. administration.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use