Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.


Chemistry - Simple, low molecular weight, cationic proteins, protamines occur naturally in thesperm of fish. Commercially available protamine sulfate is produced from protamine obtained fromthe sperm or mature testes of salmon (or related species). It occurs as a fine, white to off-whitecrystalline or amorphous powder that is sparingly soluble in water and very slightly soluble inalcohol. The injection is available as either a prepared solution with a pH of 6-7 or a lyophilizedpowder that has a pH of 6.5-7.5 after reconstituting.

Storage, Stability, Compatibility

The powder for injection should be stored at room temperature (15-30°C), and the injection (liquid) in the refrigerator (2-8°C); avoid freezing. The injection isstable at room temperature for at least 2 weeks, however. The powder for injection should be usedimmediately if reconstituted with Sterile Water for Injection and within 72 hours if reconstitutedwith Bacteriostatic Water for Injection.
Either D5W or normal saline are recommended to be used for protamine sulfate infusions.
Cimetidine HCl or Verapamil HCl are reported to be compatible with protamine sulfate for injection.


Protamine is strongly basic and heparin, strongly acidic; protamine complexeswith heparin to form an inactive stable salt. Protamine has intrinsic anticoagulant activity, but itseffects are weak and rarely cause problems.
Uses, Indications - Protamine is used in all species for the treatment of heparin overdosage whensignificant bleeding occurs. It has also been suggested to be used for Bracken Fern toxicity inruminants (see Doses).

Pharmacokinetics - PROTAMINE SULFATE

After IV injection, protamine binds to heparin within 5 minutes. The exactmetabolic fate of the heparin-protamine complex is not known, but there is evidence that thecomplex is partially metabolized and/or degraded by fibrinolysin thus freeing heparin.

Contraindications, Precautions, Reproductive Safety

Protamine is contraindicated in patientswho have demonstrated hypersensitivity or intolerance to the drug in the past.

Adverse Effects, Warnings

If protamine sulfate is injected IV too rapidly, acute hypotension, bradycardia, pulmonary hypertension and dyspnea can occur. These effects are usually absent orminimized when the drug is administered slowly (over 1-3 minutes). Hypersensitivity reactionshave also been reported.
A heparin "rebound" effect has also been reported; where anticoagulation and bleeding occurseveral hours after heparin has been apparently neutralized. This may be due to either a release ofheparin from extravascular compartments or the release of heparin from the protamine-heparincomplex.

Overdosage, Acute Toxicity

Because protamine has inherent anticoagulant activity, overdoses ofprotamine may theoretically result in hemorrhage. However, in one human study, overdoses of 600- 800 mg resulted only in mild, transient effects on coagulation. The LD50 of protamine in mice is100 mg/kg.
Drug Interactions; Drug/Laboratory Interactions - None located.

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