Protamine sulfate uses , brand name and its dose

Description of Protamine sulfate

Protamine sulfate, a protein derived from fish sperm, is a chemical antagonist of heparin. Clinically, protamine is indicated for heparin overdose and is commonly used to neutralize heparin during extracorporeal circulation following dialysis, and arterial or cardiac surgery. Dosage is guided by blood coagulation studies, with each mg of protamine sulfate neutralizing not less than 100 USP heparin units. Protamine must be administered via slow intravenous injection at a rate not to exceed 50 mg over a 10 minute period. High doses and rapid administration may result in severe hypotension, cardiovascular collapse, pulmonary edema, pulmonary vasoconstriction, and pulmonary hypertension.

Mechanism of Action of Protamine sulfate

Protamine possesses weak anticoagulant effects when administered alone; however, upon contact with heparin, it forms a salt, neutralizing the anticoagulant effect of both drugs. Protamine, a strongly basic compound, forms complexes with heparin sodium or heparin calcium, which are acidic compounds. Formation of this complex can result in disruption of the heparin-antithrombin III complex responsible for the anticoagulant activity of heparin. The protamine-heparin complex does not possess anticoagulant properties. Protamine’s anticoagulant effect usually is clinically insignificant and is likely the result of thromboplastin inhibition, which diminishes thrombin activity.

Pharmacokinetics

Protamine is administered via intravenous infusion. The onset of action is rapid, with neutralization of heparin evident within 5 minutes. The duration of action can persist up to 2 hours, depending on body temperature. The fate of the heparin-protein complex is unknown, but it appears to be partially degraded, with the release of heparin

Generic Name
Protamine Sulfate

Therapeutic Class
Heparin Antagonist

FDA-Label Indications
Toxicity of drug, Heparin: Adult

Common Effects
Dermatologic: Flushing
Gastrointestinal: Nausea, Vomiting
Respiratory: Dyspnea

Serious Effects
Cardiovascular: Bradyarrhythmia, Hypotension
Immunologic: Anaphylaxis, Non-allergic anaphylaxis, Circulatory collapse, capillary leak, noncardiogenic pulmonary edema

Administration
Intravenous: intended for use without dilution (10 mg/mL), however may be diluted in D5W or NS (do not store, contains no preservatives)
Intravenous: administer by very slow intravenous injection over 10 minutes; MAX 50 mg
Intravenous: incompatible with certain antibiotics (several cephalosporins and penicillins)

How Supplied – Trade
PremierPro Rx Protamine Sulfate: Intravenous Solution: 10 MG/1 ML
Protamine Sulfate Novaplus: Intravenous Solution: 10 MG/1 ML

How Supplied – Generic
Intravenous Solution: 10 MG/1 ML

Adult Dose
Toxicity of drug, Heparin: 1 mg of protamine sulfate will neutralize not less than 100 units of heparin; give by slow IV injection over 10 minutes up to a MAX of 50 mg per dose; if 30 minutes have elapsed since the injection of heparin, one-half the dose may be sufficient (FDA dosage)
Toxicity of drug, Low-molecular-weight heparin: (Dalteparin) 1 mg IV for every 100 anti-Xa international units of dalteparin; if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of 0.5 mg protamine sulfate per 100 anti-Xa international units of dalteparin may be administered; maximum neutralization of the anti-Factor Xa activity is about 60% to 75%

Toxicity of drug, Low-molecular-weight heparin: (Enoxaparin) 1 mg IV for every 1 mg of enoxaparin administered in the previous 8 hours; if more than 8 hours has elapsed since the last dose of enoxaparin was administered, or if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of 0.5 mg per 1 mg of enoxaparin may be administered; if more than 12 hours has elapsed since enoxaparin administration, protamine sulfate administration may not be necessary; the maximum neutralization of the anti-Factor Xa activity is about 60% .

Toxicity of drug, Low-molecular-weight heparin: (Tinzaparin) 1 mg IV for every 100 anti-Xa international units of tinzaparin; if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of 0.5 mg per 100 anti-Xa international units of tinzaparin may be administered; the maximum neutralization of the anti-Factor Xa activity is about 60% .

Pediatric Dose
General Dosage Information: safety and effectiveness in children have not been established
Toxicity of drug, Heparin: Within 30 minutes since last dose of heparin therapy, 1 mg IV for every 100 units of heparin received; between 30 and 60 minutes since last dose of heparin therapy, 0.5 to 0.75 mg for every 100 units of heparin received; between 60 and 120 minutes since the last dose of heparin, 0.375 to 0.5 mg per every 100 units of heparin received; more than 120 minutes since the last dose of heparin, 0.25 to 0.375 mg per every 100 units of heparin received; MAX 50 mg, not exceeding 5 mg/minute in a concentration of 10 mg/mL (guideline dosage)

Toxicity of drug, Low-molecular-weight heparin: Although the safety effectiveness of protamine sulfate among pediatric patients has not been approved by the US Food and Drug Administration, the American College of Chest Physicians (AACP) Evidence Based Clinical Practice Guidelines state that for treatment of low molecular weight heparin (LMWH)-induced bleeding, protamine sulfate will neutralize anti-FIIa activity and partially neutralize anti-FXa activity. Protamine sulfate dosing is dependent on the dose of the LMWH administered and repeated doses may be required .

Toxicity of drug, Low-molecular-weight heparin: (Dalteparin) 1 mg IV for every 100 anti-Xa international units of dalteparin; if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of 0.5 mg protamine sulfate per 100 anti-Xa international units of dalteparin may be administered; maximum neutralization of the anti-Factor Xa activity is about 60% to 75%
Toxicity of drug, Low-molecular-weight heparin: (Enoxaparin) 1 mg IV for every 1 mg of enoxaparin administered in the previous 8 hours; if more than 8 hours has elapsed since the last dose of enoxaparin was administered, or if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of 0.5 mg per 1 mg of enoxaparin may be administered; if more than 12 hours has elapsed since enoxaparin administration, protamine sulfate administration may not be necessary; the maximum neutralization of the anti-Factor Xa activity is about 60% .
Toxicity of drug, Low-molecular-weight heparin: (Tinzaparin) 1 mg IV for every 100 anti-Xa international units of tinzaparin; if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of 0.5 mg per 100 anti-Xa international units of tinzaparin may be administered; the maximum neutralization of the anti-Factor Xa activity is about 60% .