heparin sodium in 0.45% sodium chloride injection Adverse Reactions

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Fatal Medication Errors [see Warnings and Precautions (5.1)]
Hemorrhage [see Warnings and Precautions (5.2)]
Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) [see Warnings and Precautions (5.3)]
Thrombocytopenia [see Warnings and Precautions (5.4)]
Heparin Resistance [see Warnings and Precautions (5.6)]
Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
Hyperkalemia [see Warnings and Precautions (5.8)]

6.1 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of heparin sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hemorrhage

Hemorrhage is the chief complication that may result from heparin therapy [see Warnings and Precautions (5.2)]. An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug [see Overdosage (10)]. 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:

a.
Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued in patients who develop signs and symptoms of acute adrenal hemorrhage and insufficiency. Initiation of corrective therapy should not depend on laboratory confirmation of the diagnosis, since any delay in an acute situation may result in the patient's death.
b.
Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term anticoagulant therapy. This complication if unrecognized may be fatal.
c.
Retroperitoneal hemorrhage.

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) and Delayed Onset of HIT (With or Without Thrombosis): [see Warnings and Precautions (5.3, 5.4)]

Local Irritation

Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) injection of heparin sodium. These complications are much more common after intramuscular use, and such use is not recommended.

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 site of the feet, may occur [see Warnings and Precautions (5.7)].

Episodes of painful, ischemic, and cyanosed limbs have been reported with heparin use.

Metabolism and Nutrition Disorders – Hyperkalemia.

Elevations of Serum Aminotransferases

Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in a high percentage of patients(and healthy subjects) who have received heparin.

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 also been reported.

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation, and hypervolemia.

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Adverse Reactions

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Fatal Medication Errors [see Warnings and Precautions (5.1)]
Hemorrhage [see Warnings and Precautions (5.2)]
Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) [see Warnings and Precautions (5.3)]
Thrombocytopenia [see Warnings and Precautions (5.4)]
Heparin Resistance [see Warnings and Precautions (5.6)]
Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
Hyperkalemia [see Warnings and Precautions (5.8)]

6.1 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of heparin sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hemorrhage

Hemorrhage is the chief complication that may result from heparin therapy [see Warnings and Precautions (5.2)]. An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug [see Overdosage (10)]. 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:

a.
Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued in patients who develop signs and symptoms of acute adrenal hemorrhage and insufficiency. Initiation of corrective therapy should not depend on laboratory confirmation of the diagnosis, since any delay in an acute situation may result in the patient's death.
b.
Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term anticoagulant therapy. This complication if unrecognized may be fatal.
c.
Retroperitoneal hemorrhage.

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) and Delayed Onset of HIT (With or Without Thrombosis): [see Warnings and Precautions (5.3, 5.4)]

Local Irritation

Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) injection of heparin sodium. These complications are much more common after intramuscular use, and such use is not recommended.

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 site of the feet, may occur [see Warnings and Precautions (5.7)].

Episodes of painful, ischemic, and cyanosed limbs have been reported with heparin use.

Metabolism and Nutrition Disorders – Hyperkalemia.

Elevations of Serum Aminotransferases

Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in a high percentage of patients(and healthy subjects) who have received heparin.

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 also been reported.

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation, and hypervolemia.

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