Brand and Other Names:
- Classes: Antidotes, Other
Dosing & Uses
Dosage Forms & Strengths
- 10 mg/mL
1-1.5 mg per 100 USP units of heparin; not to exceed 50 mg
Monitor APTT 5-15 min after dose then in 2-8 hr
In accidental overdoses of heparin, consider t1/2 heparin 60-90 min
In setting without bleeding complications, consider observation, rather than reversal of anticoagulation with protamine (avoids ADR's)
Complex of protamine and heparin may degrade over time requiring further doses
Dalteparin or Tinzaparin Overdose
1 mg protamine for 100 units dalteparin or tinzaparin; if PTT prolonged 4hr after protamine overdose administer 0.5 mg per 100 units of dalteparin or tinzaparin
1 mg per mg enoxaparin (if enoxaparin overdose given within 8 hr); if >8 hr of overdose or bleeding continues after 4 hr after first dose, give 0.5 mg protamine per mg enoxaparin
Time Elapsed Since Heparin Dose
Dose of protamine (mg) to neutralize 100 units of heparin
- <1/2 hr: 1-1.5 mg/100 units of heparin
- 30-120 min: 0.5-0.75 mg/100 units of heparin
- >2 hr: 0.25-0.375 mg/100 units of heparin
Dosage Forms & Strengths
- 10 mg/mL
Heparin Neutralization (Off-label)
~1 mg protamine neutralizes 100 units of heparin; not to exceed 50 mg/dose
Monagle P, et al. Chest 2008:133(6 Suppl):S887-S968
Time elapsed since heparin dose
- Protamine dose to neutralize 100 units of heparin
- <1/2 hr: 1 mg
- 30-120 min: 0.5-0.75 mg
- >2 hr: 0.25-0.375 mg
Serious - Use Alternative
Significant - Monitor Closely
Frequency Not Defined
Decreased O2 consumption
Black Box Warnings
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, 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, 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 should not be given when bleeding occurs without prior heparin use
Heparin rebound causing bleeding may occur 8-9 hr after protamine administration
May be ineffective in cardiac surgery patients despite adequate dose
Rapid infusion reactions can cause severe hypotensive reactions
Pregnancy & Lactation
Pregnancy Category: C
Lactation: not known if excreted in breast milk
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Protamine that is strongly basic combines with acidic heparin forming a stable complex and neutralizes the anticoagulant activity of both drugs
Half-life elimination: 7 min
Onset: 5 min
Duration: 2 hr
Vd: 5.4 L
Clearance: 1.4 L/min
Additive: cephalosporins, penicillins
Syringe: diatrizoate meglumine 52%, diatrizoate sodium, ioxaglate meglumine 39.3%, ioxaglate sodium 19.6%
Reconstitute with 5 mL sterile water
Resulting solution equals 10 mg/mL
Inject without further dilution over 1-3 min; maximum of 50 mg in any 10 min period
For IV use only
Administer slow IVP (50 mg over 10 min)
Rapid IV infusion causes hypotension
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