Protamine Sulfate (1 brand name, 3 dosage forms, 2 routes)
Available dosage forms: SOLUTION, Injectable, POWDER.
Routes of administration: INTRAVENOUS, Injection.
Brand Names
- PROTAMINE SULFATE
Boxed Warning
Protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension. Risk factors include high dose or overdose, rapid administration (see WARNINGS and DOSAGE AND ADMINISTRATION ), repeated doses, previous administration of protamine, and current or previous use of protamine-containing drugs (NPH insulin, protamine zinc insulin, and certain beta-blockers). Allergy to fish, previous vasectomy, and severe left ventricular dysfunction and abnormal preoperative pulmonary hemodynamics also may be risk factors. In patients with any of these risk factors, the risk to benefit of administration of protamine sulfate should be carefully considered. Vasopressors and resuscitation equipment should be immediately available in case of a severe reaction to protamine. Protamine sulfate should not be given when bleeding occurs without prior heparin use.
Indications and Usage
Protamine Sulfate Injection, USP is indicated in the treatment of heparin overdosage.
Dosage and Administration
Each mg of protamine sulfate, calculated on the dried basis, neutralizes not less than 100 USP Heparin Units. Protamine sulfate injection should be given by very slow intravenous injection over a 10-minute period in doses not to exceed 50 mg (see WARNINGS ). Protamine sulfate is intended for injection without further dilution; however, if further dilution is desired, D5-W or normal saline may be used. Diluted solutions should not be stored since they contain no preservative. Protamine sulfate should not be mixed with other drugs without knowledge of their compatibility, because protamine sulfate has been shown to be incompatible with certain antibiotics, including several of the cephalosporins and penicillins. Because heparin disappears rapidly from the circulation, the dose of protamine sulfate required also decreases rapidly with the time elapsed following intravenous injection of heparin. For example, if the protamine sulfate is administered 30 minutes after the heparin, one-half the usual dose may be sufficient. The dosage of protamine sulfate should be guided by blood coagulation studies (see WARNINGS ). Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.
Contraindications
Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug.
Adverse Reactions
To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The intravenous administration of protamine sulfate may cause a sudden fall in blood pressure and bradycardia. Other reactions include transitory flushing and feeling of warmth, dyspnea, nausea, vomiting and lassitude. Back pain has been reported in conscious patients undergoing such procedures as cardiac catheterization. Severe adverse reactions have been reported including: (1) Anaphylaxis that resulted in severe respiratory distress, circulation collapse and capillary leak (see PRECAUTIONS ). Fatal anaphylaxis has been reported in one patient with no prior history of allergies; (2) Anaphylactoid reactions with circulatory collapse, capillary leak, and noncardiogenic pulmonary edema; acute pulmonary hypertension. Complement activation by the heparin-protamine complexes, release of lysosomal enzymes from neutrophils, and prostaglandin and thomboxane generation have been associated with the development of anaphylactoid reactions. Severe and potentially irreversible circulatory collapse associated with myocardial failure and reduced cardiac output can also occur. The mechanism(s) of this reaction and the role played by concurrent factors are unclear. High-protein, noncardiogenic pulmonary edema associated with the use of protamine has been reported in patients on cardiopulmonary bypass who are undergoing cardiovascular surgery. The etiologic role of protamine in the pathogenesis of this condition is uncertain, and multiple factors have been present in most cases. The condition has been reported in association with administration of certain blood products, other drugs, cardiopulmonary bypass alone, and other etiologic factors. It is difficult to treat, and it can be life-threatening. Because fatal anaphylactic and anaphylactoid reactions have been reported after the administration of protamine sulfate, the drug should be given only
Overdosage
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.