6.1 Postmarketing Experience

The following adverse reactions have been identified during post approval use of HEPARIN SODIUM INJECTION. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

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Hemorrhage – Hemorrhage is the chief complication that may result from heparin therapy [see Warnings and Precautions (5.2)]. Gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect including:

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Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred with heparin therapy, including fatal cases.

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Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term heparin therapy.

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Retroperitoneal hemorrhage.

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HIT and HITT, including delayed onset cases [see Warnings and Precautions (5.3)].

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Local irritation – Local irritation, erythema, mild pain, hematoma, or ulceration have occurred following deep subcutaneous (intrafat) injection of heparin sodium. Because such reactions occur more frequently after intramuscular administration, the IM route is not recommended.

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Histamine-like reactions – Such reactions have been observed at the site of injection. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin, occasionally requiring skin grafting [see Warnings and Precautions (5.3)].

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

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Metabolism and Nutrition Disorders – Hyperkalemia.

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Elevations of serum aminotransferases – Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in patients who have received heparin.

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Others – Osteoporosis following long-term administration of high doses of heparin, cutaneous necrosis after systemic administration, suppression of aldosterone synthesis, delayed transient alopecia, priapism, and rebound hyperlipemia on discontinuation of heparin sodium have been reported.