protamine sulfate

Indications

• reversal of severe heparin overdose
  • most cases are managed by stopping heparin administration
• reversal of LMW heparin toxicity
• reversal of heparin effects after surgery or dialysis

Contraindications

• fondaparinux toxicity

Pregnancy category: C)

Safety in lactation: ?

Dosage

• 10-50 mg IV over 10 minutes
• 1 mg antagonizes approximately
  • 100 U of heparin,
  • 100 U of dalteparin
  • 100 U of tinzaparin
  • 1 mg of enoxaparin
• doses > 100 mg produce paradoxical anticoagulation
• for subcutaneous heparin overdose, dosage may need to be repeated

Injection: 10 mg/mL (5 mL, 25 mL).

Pharmacokinetics

• elimination: plasma
• neutralization of heparin occurs within 5 minutes of IV administration
• duration of action: 2 hours (dependent upon body temperature)

Adverse effects

• common (> 10%)
  • hypotension, dyspnea, bradycardia
• less common (1-10%)
  • hemorrhage
• uncommon (< 1%)
  • flushing, lassitude, nausea/vomiting, pulmonary hypertension, hypersensitivity reactions

Mechanism of action

• binds to heparin forming a stable salt which has no anticoagulant activity
• protamine given in excess has anticoagulant properties

More general terms

• hematologic agent
• antidote

Additional terms

• protamine