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Pregnancy Category: C
Acute management of severe heparin overdosage.Used to neutralize heparin received during dialysis, cardiopulmonary bypass, and other procedures.Management of overdose of heparin-like compounds.
A strong base that forms a complex with heparin (an acid).
Inactivation of heparin.
Absorption: Administered IV only, resulting in complete bioavailability.
Metabolism and Excretion: Metabolic fate not known. Protamine-heparin complex eventually degrades.
Time/action profile (reversal of heparin effect)
|IV||30 sec–1 min||unknown||2 hr†|
Contraindicated in: Hypersensitivity to protamine or fish.
Use Cautiously in: Patients who have received previous protamine-containing insulin or vasectomized men (↑ risk of hypersensitivity reactions); Obstetric / Lactation / Pediatric: Safety not established.
Adverse Reactions/Side Effects
- pulmonary hypertension
- back pain
- hypersensitivity reactions, including anaphylaxis (life-threatening)
- angioedema, and pulmonary edema (life-threatening)
Drug-Drug interactionNone significant.
Intravenous (Adults and Children) Heparin overdose—1 mg/100 units of heparin. If given >30 min after heparin, give 0.5 mg/100 units of heparin (not to exceed 100 mg/2 hr). Further doses should be determined by coagulation tests. If heparin was administered subcutaneously, use 1–1.5 mg protamine per 100 units of heparin, give 25–50 mg of the protamine dose slowly followed by a continuous infusion over 8–16 hr. Enoxaparin overdose—1 mg/each mg of enoxaparin to be neutralized (unlabeled). Dalteparin overdose—1 mg/100 anti-Xa IU of dalteparin. If required, a second dose of 0.5 mg/100 anti-Xa IU of dalteparin may be given 2–4 hr later if laboratory assessment indicates need (unlabeled).
Availability (generic available)
Injection: 10 mg/mL
- Assess for bleeding and hemorrhage throughout therapy. Hemorrhage may recur 8–9 hr after therapy because of rebound effects of heparin. Rebound may occur as late as 18 hr after therapy in patients heparinized for cardiopulmonary bypass.
- Assess for allergy to fish (salmon), previous reaction to or use of protamine insulin or protamine sulfate. Vasectomized and infertile men also have higher risk of hypersensitivity reaction.
- Observe patient for signs and symptoms of hypersensitivity reaction (hives, edema, coughing, wheezing). Keep epinephrine, an antihistamine, and resuscitative equipment close by in the event of anaphylaxis.
- Assess for hypovolemia before initiation of therapy. Failure to correct hypovolemia may result in cardiovascular collapse from peripheral vasodilating effects of protamine sulfate.
- Lab Test Considerations: Monitor clotting factors, activated clotting time (ACT), activated partial thromboplastin time (aPTT), and thrombin time (TT) 5–15 min after therapy and again as necessary.
Potential Nursing DiagnosesRisk for injury (Indications)
Ineffective tissue perfusion (Indications)
- Do not confuse protamine with Protonix (pantoprazole).
- Discontinue heparin infusion. In milder cases, overdosage may be treated by heparin withdrawal alone.
- In severe cases, fresh frozen plasma or whole blood may also be required to control bleeding.
- Dose varies with type of heparin, route of heparin therapy, and amount of time elapsed since discontinuation of heparin.
- Do not administer >100 mg in 2 hr without rechecking clotting studies, as protamine sulfate has its own anticoagulant properties.
- pH: 6.0–7.0.
- Diluent: May be administered undiluted. If further dilution is desired, D5W or 0.9% NaCl may be used.Concentration: 10 mg/mL.
- Rate: Administer by slow IV push over 1–3 min. Rapid infusion rate may result in hypotension, bradycardia, flushing, or feeling of warmth. If these symptoms occur, stop infusion and notify physician. No more than 50 mg should be administered within a 10-min period.
- Y-Site Compatibility: alfentanil, amikacin, aminophylline, ascorbic acid, atropine, azathioprine, aztreonam, benztropine, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, ceftazidime, chlorpromazine, clindamycin, cyanocobalamin, cyclosporine, digoxin, diphenhydramine, dobutamine, dopamine, doxycycline, enalaprilat, ephedrine, epinephrine, epoetin alfa, erythromycin, esmolol, famotidine, fentanyl, fluconazole, ganciclovir, gentamicin, glycopyrrolate, imipenem/cilastatin, isoproterenol, labetalol, lidocaine, magnesium sulfate, mannitol, meperidine, metaraminol, methoxamine, methyldopate, metoclopramide, metoprolol, midazolam, morphine, multivitamins, nalbuphine, naloxone, nitroglycerin, nitroprusside, norepinephrine, ondansetron, oxytocin, papaverine, pentazocine, phentolamine, phenylephrine, potassium chloride, procainamide, prochlorperazine, promethazine, propranolol, pyridoxime, ranitidine, sodium bicarbonate, succinylcholine, sufentanil, tobramycin, tolazoline, trimetaphan, vancomycin, vasopressin, verapamil
- Y-Site Incompatibility: amphotericin B colloidal, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, cefoxitin, ceftazidime, cefuroxime, chloramphenicol, dantrolene, dexamethasone sodium phosphate, diazepam, diazoxide, folic acid, furosemide, heparin, hydrocortisone sodium succinate, indomethacin, insulin, ketorolac, methylprednisolone sodium succinate, nafcillin, oxacillin, penicillin G, pentamidine, pentobarbital, phenobarbital, phenytoin, ticarcillin/clavulanate, trimethoprim/sulfamethoxazole
- Explain purpose of the medication to patient. Instruct patient to report recurrent bleeding immediately.
- Advise patient to avoid activities that may result in bleeding (shaving, brushing teeth, receiving injections or rectal temperatures, or ambulating) until risk of hemorrhage has passed.
- Control of bleeding.
- Normalization of clotting factors in heparinized patients.
a purified mixture of simple protein principles from the sperm or testes of suitable species of fish; it is a heparin antagonist used in certain hemorrhagic states associated with increased amounts of heparinlike substances in the circulation and for the treatment of heparin overdosage.
a heparin antagonist derived from fish sperm.
indication It is prescribed to diminish or reverse the anticoagulant effect of heparin, particularly in cases of heparin overdosage.
contraindications Pregnancy, allergy to fish, or known hypersensitivity to this drug prohibits its use.
adverse effects Among the more serious adverse effects are hypotension, dyspnea, and bradycardia. Dosage greater than needed to neutralize heparin causes the toxic and anticoagulant effects of protamine.
A purified form of protamine used to neutralize the anticoagulant action of heparin.
See also: protamine