Description

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. 

---

NDA 17-037/S-158 
Page 9 
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. 
DOSAGE AND ADMINISTRATION 
Parenteral drug products should be inspected visually for particulate matter and discoloration 
prior to administration, whenever solution and container permit. Slight discoloration does not 
alter potency. 
When heparin is added to an infusion solution for continuous intravenous administration, the container 
should be inverted at least six times to ensure adequate mixing and prevent pooling of the heparin in 
the solution. 
Heparin sodium is not effective by oral administration and should be given by intermittent intravenous 
injection, intravenous infusion, or deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal 
fat layer) injection. The intramuscular route of administration should be avoided because of the