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Protamine sulfate

Classification

Antidote

Indications

CCP: Neutralization of heparin secondary to an overdose

Contraindications

Hypersensitivity

Adult dosages

CCP: Neutralization of heparin secondary to an overdose

Dosage of protamine is based on heparin dose.

1 mg protamine neutralizes 100 U heparin
Slow IV push over 10 minutes
Max dose 50 mg

Pediatric Considerations And Dosing

CCP: Neutralization of heparin secondary to an overdose

Dosage of protamine is based on heparin dose and time since heparin administration.

Time Since Last Heparin Dose	Dose of Protamine
<30 minutes	IV: 1 mg of protamine per 100 units of heparin; maximum dose: 50 mg/dose
30 to 60 minutes	IV: 0.5 to 0.75 mg of protamine per 100 units of heparin; maximum dose: 50 mg/dose
60 to 120 minutes	IV: 0.375 to 0.5 mg of protamine per 100 units of heparin; maximum dose: 50 mg/dose
>120 minutes	IV: 0.25 to 0.375 mg of protamine per 100 units of heparin; maximum dose: 50 mg/dose

Mechanism Of Action

Protamine is a highly alkaline protein molecule with a large positive charge and a weak anticoagulant activity when administered alone. When protamine is given in the presence of heparin (strongly acidic and negatively charged), a stable salt is formed, and the anticoagulant activity of both drugs is nullified. In the presence of LMWH, protamine incompletely reverses the anti-factor Xa activity of LMWH.

Pharmacokinetics

Onset: 5 minutes

Half-life: 7 minutes

Adverse Effects

Cardiovascular

Bradycardia, flushing, hypotension, sudden decrease of blood pressure

Central nervous system

Lassitude

Gastrointestinal

Nausea, vomiting

Hematologic & oncologic

Hemorrhage

Hypersensitivity

Hypersensitivity reaction

Respiratory

Dyspnea, pulmonary hypertension

Warning And Precautions

Heparin rebound
Hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, pulmonary vasoconstriction, and pulmonary hypertension may occur. Risk factors for such events include use of high doses or overdose, repeated doses, previous protamine administration.
Too rapid administration can cause severe hypotensive and anaphylactoid-like reactions.
May be ineffective in some patients following cardiac surgery despite adequate doses.
In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity.
It is not known if protamine is excreted in breast milk.

Drug Interactions

No know significant drug interactions.

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Protamine sulfate

Classification

Indications

Contraindications

Adult dosages

Pediatric Considerations And Dosing

Mechanism Of Action

Pharmacokinetics

Adverse Effects

Warning And Precautions

Drug Interactions