Description

Hypersensitivity 
Generalized hypersensitivity reactions have been reported, with chills, fever and urticaria as the most 
usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea and vomiting, and 
anaphylactoid reactions, including shock, occurring more rarely. Itching and burning, especially on the 
plantar side of the feet, may occur.

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NDA 17-037/S-158 
Page 29 
Thrombocytopenia has been reported to occur in patients receiving heparin, with a reported incidence 
of 0 to 30%. While often mild and of no obvious clinical significance, such thrombocytopenia can be 
accompanied by severe thromboembolic complications such as skin necrosis, gangrene of the 
extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, and 
possibly death. (See WARNINGS and PRECAUTIONS.) 
Certain episodes of painful, ischemic and cyanosed limbs have in the past been attributed to allergic 
vasospastic reactions. Whether these are in fact identical to the thrombocytopenia-associated 
complications remains to be determined. 
OVERDOSAGE 
Symptoms 
Bleeding is the chief sign of heparin overdosage. Nosebleeds, blood in urine or tarry stools may be 
noted as the first sign of bleeding. Easy bruising or petechial formations may precede frank bleeding. 
Treatment—Neutralization of Heparin Effect 
When clinical circumstances (bleeding) require reversal of heparinization, protamine sulfate (1% 
solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be 
administered, very slowly, in any 10-minute period. Each mg of protamine sulfate neutralizes 
approximately 100 USP heparin units. The amount of protamine required decreases over time as 
heparin is metabolized. Although the metabolism of heparin is complex, it may, for the purpose of 
choosing a protamine dose, be assumed to have a half-life of about 1/2 hour after intravenous injection. 
Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. 
Because fatal reactions often resembling anaphylaxis have been reported, the drug should be given 
only when resuscitation techniques and treatment of anaphylactoid shock are readily available. 
For additional information consult the labeling of Protamine Sulfate Injection, USP products.