Label Changes for:

Heparin Sodium Injection

December 2011

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – June 2010, February and December 2011

 

December 2011 

 

Heparin Sodium Products

  • Heparin Sodium Injection
  • Heparin Sodium in 0.45% Sodium Chloride Injection
  • Heparin Sodium in 5% Dextrose Injection
  • Heparin Sodium in 0.9% Sodium Chloride Injection
  • Heparin Sodium in 5% Dextrose, Injection
  • Heparin Sodium in 0.9% Sodium Chloride Injection
  • Heparin Sodium in 5% Dextrose Injection

 Class label changes, please refer to specific labels for slight differences in sections

WARNINGS

Fatal Medication Errors
  • Do not use Heparin Sodium Injection as a “catheter lock flush” product. Heparin Sodium Injection is supplied in vials containing various strengths of heparin, including vials that contain a highly concentrated solution of 10,000 units in 1 mL. Fatal hemorrhages have occurred in pediatric patients due to medication errors in which 1 mL Heparin Sodium Injection vials were confused with 1 mL “catheter lock flush” vials. Carefully examine all Heparin Sodium Injection vials to confirm the correct vial choice prior to administration of the drug.
Benzyl Alcohol Toxicity
  • Use preservative-free Heparin Sodium Injection in neonates and infants. The preservative benzyl alcohol has been associated with serious adverse events and death in pediatric patients. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth weight infants may be more likely to develop toxicity.

 

PRECAUTIONS

Pregnancy
  • Pregnancy Category C
  • There are no adequate and well-controlled studies on heparin use in pregnant women. In published reports, heparin exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes in humans. Heparin sodium does not cross the placenta based on human and animal studies. Administration of heparin to pregnant animals at doses higher than the maximum human daily dose based on body weight resulted in increased resorptions. Use heparin sodium during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • If available, preservative-free Heparin Sodium Injection is recommended when heparin therapy is needed during pregnancy. There are no known adverse outcomes associated with fetal exposure to the preservative benzyl alcohol through maternal drug administration; however, the preservative benzyl alcohol can cause serious adverse events and death when administered intravenously to neonates and infants.
  • In a published study conducted in rats and rabbits, pregnant animals received heparin intravenously during organogenesis at a dose of 10,000 units/kg/day, approximately 10 times the maximum human daily dose based on body weight. The number of early resorptions increased in both species. There was no evidence of teratogenic effects.

Nursing Mothers

  • If available, preservative-free Heparin Sodium Injection is recommended when heparin therapy is needed during lactation. Due to its large molecular weight, heparin is not to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant. Exercise caution when administering Heparin Sodium Injection to a nursing mother.

Pediatric Use

  • There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience.
  • Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which Heparin Sodium Injection vials have been confused with “catheter lock flush” vials.

Benzyl Alcohol Toxicity

  • Use preservative-free Heparin Sodium Injection in neonates and infants. The preservative benzyl alcohol has been associated with serious adverse events and death in pediatric patients. The “gasping syndrome” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight infants. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.
  • Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth weight infants may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

 

February 2011

 

WARNINGS

  • Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) HIT is a serious immune-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as HIT with thrombosis. Thrombotic events may also be the initial presentation for HIT. These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and fatal outcomes. Once HIT (with or without thrombosis) is diagnosed or strongly suspected, all heparin sodium sources (including heparin flushes) should be discontinued and an alternative anticoagulant used. ...

 

June 2010

 

CONTRAINDICATIONS

Pregnancy, Nursing Mothers, and Pediatric Use
  • Do not administer Heparin Sodium Injection, USP (porcine), preserved with benzyl alcohol to neonates, infants, pregnant women, or nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. Heparin Sodium Injection, USP (porcine), preservative free, when indicated, should be used in these populations.

 

PRECAUTIONS

Pregnancy
  • Do not administer Heparin Sodium Injection, USP (porcine), preserved with benzyl alcohol, to pregnant women. Heparin Sodium Injection, USP (porcine), preservative free, when indicated, should be administered to pregnant women
Nursing Mothers
  • Do not administer Heparin Sodium Injection, USP (porcine), preserved with benzyl alcohol, to nursing mothers. Heparin Sodium Injection, USP (porcine), preservative free, when indicated, should be administered to nursing mothers.
Pediatric Use
  • Do not administer Heparin Sodium Injection, USP (porcine), preserved with benzyl alcohol, to neonates and infants. Heparin Sodium Injection, USP (porcine), preservative free, when indicated, should be administered to neonates and infants. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. The "gasping syndrome," (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birthweight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.
  • Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

 

 

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