Classifications: antidote;
Therapeutic: antidote

Pregnancy Category: C


10 mg/mL injection


Because protamine is strongly basic, it combines with strongly acidic heparin to produce a stable complex; thus anticoagulant effect of both drugs is neutralized.

Therapeutic Effect

Effective antidote to heparin overdose.


Antidote for heparin overdosage (after heparin has been discontinued).

Unlabeled Uses

Antidote for heparin administration during extracorporeal circulation.


Hemorrhage not induced by heparin overdosage; pregnancy (category C); lactation.

Cautious Use

Cardiovascular disease; history of allergy to fish; vasectomized or infertile males; diabetes mellitus; patients who have received protamine-containing insulin.

Route & Dosage

Antidote for Heparin Overdose
Adult/Child: IV 1 mg for every 100 units of heparin to be neutralized (max: 100 mg in a 2 h period), give the first 25–50 mg by slow direct IV and the rest over 2–3 h


Note: Titrate dose carefully to prevent excess anticoagulation because protamine has a longer half-life than heparin and also has some anticoagulant effect of its own.


Note: Verify correct IV concentration and rate of infusion for infants or children with physician.

PREPARE: Direct: May be given as supplied direct IV.  Continuous: Dilute in 50 mL or more of NS or D5W.  

ADMINISTER: Direct: Give each 50 mg or fraction thereof slowly over 10–15 min. NEVER give more than 50 mg in any 10 min period or 100 mg in any 2 h period.  Continuous: Do not exceed direct rate. Give over 2–3 h or longer as determined by coagulation studies.  

INCOMPATIBILITIES Solution/additive: radiocontrast materials, furosemide.

  • Store protamine sulfate injection at 15°–30° C (59°–86° F).
  • Solutions do not contain preservatives and should not be stored.

Adverse Effects (≥1%)

CV: Abrupt drop in BP (with rapid IV infusion), bradycardia. Body as a Whole: Urticaria, angioedema, pulmonary edema, anaphylaxis, dyspnea, lassitude; transient flushing and feeling of warmth. GI: Nausea, vomiting. Hematologic: Protamine overdose or "heparin rebound" (hyperheparinemia).


No clinically significant interactions established.


Onset: 5 min. Duration: 2 h.

Nursing Implications

Assessment & Drug Effects

  • Do not use protamine if only minor bleeding occurs during heparin therapy because withdrawal of heparin will usually correct minor bleeding within a few hours.
  • Monitor BP and pulse q15–30min, or more often if indicated. Continue for at least 2–3 h after each dose, or longer as dictated by patient's condition. Be prepared to treat patient for shock as well as hemorrhage.
  • Lab tests: Monitor effect of protamine in neutralizing heparin by aPTT or ACT values. Coagulation tests are usually performed 5–15 min after administration of protamine, and again in 2–8 h if desirable.
  • Observe patients undergoing extracorporeal dialysis or patients who have had cardiac surgery carefully for bleeding (heparin rebound). Even with apparent adequate neutralization of heparin by protamine, bleeding may occur 30 min to 18 h after surgery. Monitor vital signs closely. Additional protamine may be required in these patients.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

© 2006-2022 Last Updated On: 11/22/2022 (0)
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