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Heparin (Heparin Sodium) - Drug Interactions, Contraindications, Overdosage, etc



HEPARIN drug label information in our database does not contain a dedicated section on drug interactions. Please check subsections of WARNINGS AND PRECAUTIONS as well as other sources.



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.


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.


Heparin sodium should NOT be used in patients with the following conditions:

Severe thrombocytopenia;

When suitable blood coagulation tests, e.g., the whole blood clotting time, partial thromboplastin time, etc., cannot be performed at appropriate intervals (this contraindication refers to full-dose heparin; there is usually no need to monitor coagulation parameters in patients receiving low-dose heparin);

An uncontrollable active bleeding state (see WARNINGS ), except when this is due to disseminated intravascular coagulation.


  1. Tahata T, Shigehito M, Kusuhara K, Ueda Y, et al.  Delayed-Onset of Heparin Induced Thrombocytopenia - A Case Report - J Jpn Assn Torca Surg. 1992;40(3):110-111.
  2. Warkentin T, Kelton J. Delayed-Onset Heparin-Induced Thrombocytopenia and Thrombosis.  Annals of Internal Medicine . 2001;135:502-506.
  3. Rice L, Attisha W, Drexler A, Francis J. Delayed-Onset Heparin Induced Thrombocytopenia.  Annals of Internal Medicine , 2002;136:210-215.
  4. Dieck J., C. Rizo-Patron, et al. (1990). "A New Manifestation and Treatment Alternative for Heparin-Induced Thrombosis." Chest 98(1524-26).
  5. Smythe M, Stephens J, Mattson.  Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Emergency Medicine , 2005;45 (4): 417-419.
  6. Divgi A. (Reprint), Thumma S., Hari P., Friedman K. Delayed Onset Heparin-Induced Thrombocytopenia (HIT) Presenting After Undocumented Drug Exposure as Post-Angiography Pulmonary Embolism. Blood . 2003;102(11):127b.

N+ and NOVAPLUS are registered trademarks of Novation, LLC.

Manufactured by:

Fresenius Kabi USA, LLC

Lake Zurich, IL 60047 

For Product Inquiry: 1-800-551-7176


Revised: April 2014


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