Parenteral Manual

Protamine sulphate

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Antidote (heparin)
Original Date: 
August 2005
  • Treatment of heparin or low molecular weight heparin (LMWH) overdosage   
Reconstitution and Stability: 
  • Available as a 10 mg/mL solution
  • Refrigerate, stable at room temperature for 2 weeks

- Solutions Compatible: D5W, NS

- DO NOT mix with any other drugs


(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)



IV Push

Usual dilution: < 10 mg/mL
Infusion time: 1-3 minutes
Infusion rate: do not exceed 5 mg/minute

IV Intermittent Infusion YES
Usual dilution: 0.1-10 mg/mL
Infusion time: 10-15 minutes
Infusion rate: do not exceed 5 mg/minute
IV Continuous Infusion NO

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

Heparin Reversal:  
- Dose based on amount of heparin infused and time since the last dose or end of infusion

  • 1 mg protamine neutralizes approximately 90 units of heparin (bovine lung tissue)
  • 1 mg protamine neutralizes approximately 115 units of heparin (porcine intestinal mucosa)
  • 1 mg protamine neutralizes approximately 1 mg LMWH
  • Maximum dose 50 mg in any 10 minute period
  • May repeat dosage at intervals of 15 minutes or longer
  • If heparin is administered by deep SC injection, use 1-1.5 mg protamine per 100 units of heparin

Time Elapsed

Dose of Protamine (mg) to neutralize 100 units of Heparin

Dose of Protamine (mg) to neutralize 1 mg LMWH

Few minutes



30-60 minutes



60-120 minutes 0.375-0.5 ---

>2 hours



Within last 3-4 hours


1 (a second dose of 0.5 mg protamine per 1 mg LMWH may be given if APTT remains prolonged 2-4 hours after the first dose)

Potential hazards of parenteral administration: 
  • May cause severe hypotension, bradycardia, dyspnea and transitory flushing if given by rapid IV injection      
  • Large doses (>100 mg) can produce a paradoxical anticoagulation                                               
  • Hypersensitivity reactions    
  • Nausea, vomiting, lethargy                                                                                
  • Use with caution in patients with a history of allergy to fish or previous reactions to protamine insulin
  • Heparin effect may exceed that of protamine sulphate and additional protamine sulphate may be required
  • Since heparin disappears rapidly from the circulation, the dose of protamine sulphate required also decreases rapidly with the time elapsed following the injection of heparin (eg. if protamine sulphate is administered 30 minutes after the heparin, one-half the usual dose may be sufficient)
  • Onset of heparin neutralization: within 5 minutes
  • Monitor coagulation tests, blood pressure during administration

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