After reviewing the laboratory reports of a patient who was prescribed long-term heparin therapy

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Fatal Medication Errors

Do not use this product as a “catheter lock flushâ€Â product. Heparin is supplied in various strengths. Fatal hemorrhages have occurred due to medication errors. Carefully examine all heparin products to confirm the correct container choice prior to administration of the drug.

Hemorrhage

Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks.

Hemorrhage, including fatal events, has occurred in patients receiving Heparin Sodium. Hemorrhage can occur at virtually any site in patients receiving heparin. Adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy with heparin [see ADVERSE REACTIONS]. A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age [see CLINICAL PHARMACOLOGY]. An unexplained fall in hematocrit or fall in blood pressure should lead to serious consideration of a hemorrhagic event.

Use heparin sodium with caution in disease states in which there is increased risk of hemorrhage, including:

• Cardiovascular — Subacute bacterial endocarditis, severe hypertension.
• Surgical — During and immediately following (a) spinal tap or spinal anesthesia or (b) major surgery, especially involving the brain, spinal cord or eye.
• Hematologic — Conditions associated with increased bleeding tendencies, such as hemophilia, thrombocytopenia and some vascular purpuras.
• Patients with hereditary antithrombin III deficiency receiving concurrent antithrombin III therapy — The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency. To reduce the risk of bleeding, reduce the heparin dose during concomitant treatment with antithrombin III (human).
• Gastrointestinal — Ulcerative lesions and continuous tube drainage of the stomach or small intestine.
• Other — Menstruation, liver disease with impaired hemostasis.

Heparin-Induced Thrombocytopenia (HIT) And Heparin-Induced Thrombocytopenia and Thrombosis (HITT)

HIT is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT occurs in patients treated with heparin and is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation. HIT may progress to the development of venous and arterial thromboses, a condition known as heparin-induced thrombocytopenia and thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT. These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, thrombus formation on a prosthetic cardiac valve, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. Monitor thrombocytopenia of any degree closely. If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant.

HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT or HITT.

Thrombocytopenia

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of up to 30%. It can occur 2 to 20 days (average 5 to 9) following the onset of heparin therapy. Obtain platelet counts before and periodically during heparin therapy. Monitor thrombocytopenia of any degree closely. If the count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and, if necessary, administer an alternative anticoagulant [see WARNINGS AND PRECAUTIONS].

Coagulation Testing and Monitoring

When using a full dose heparin regimen, adjust the heparin dose based on frequent blood coagulation tests. If the coagulation test is unduly prolonged or if hemorrhage occurs, heparin sodium should be discontinued promptly [see OVERDOSAGE]. Periodic platelet counts, hematocrits are recommended during the entire course of heparin therapy [see DOSAGE AND ADMINISTRATION].

Heparin Resistance

Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer, in postsurgical patients, and patients with antithrombin III deficiency. Close monitoring of coagulation tests is recommended in these cases. Adjustment of heparin doses based on anti-Factor Xa levels may be warranted.

Hypersensitivity

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations [see ADVERSE REACTIONS]. Because heparin sodium is derived from animal tissue, monitor for signs and symptoms of hypersensitivity when it is used in patients with a history of allergy.

Heparin Sodium In 5% Dextrose Injection

This product contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of heparin. Also, no studies in animals have been performed concerning mutagenesis or impairment of fertility.

Use In Specific Populations

Pregnancy

There are no available data on heparin sodium use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In published reports, heparin exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes in humans. No teratogenicity, but early embryo-fetal death was observed in animal reproduction studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses approximately 10 times the maximum recommended human dose (MRHD) of 40,000 units/24 hours infusion (see Data). Consider the benefits and risks of Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection to a pregnant woman and possible risks to the fetus when prescribing Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection to a pregnant woman.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Human Data

The maternal and fetal outcomes associated with uses of heparin via various dosing methods and administration routes during pregnancy have been investigated in numerous studies. These studies generally reported normal deliveries with no maternal or fetal bleeding and no other complications.

Animal Data

In a published study conducted in rats and rabbits, pregnant animals received heparin intravenously during organogenesis at a dose of 10,000 USP 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.

Lactation

There is no information regarding the presence of Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection in human milk, the effects on the breastfed infant, or the effects on milk production. Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection and any potential adverse effects on the breastfed infant from Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection or from the underlying maternal condition [see Use In Specific Populations].

Pediatric Use

There are no adequate and well-controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience [see DOSAGE AND ADMINISTRATION].

Geriatric Use

There are limited adequate and well-controlled studies in patients 65 years and older. However, a higher incidence of bleeding has been reported in patients over 60 years of age, especially women [see WARNINGS AND PRECAUTIONS]. Lower doses of heparin may be indicated in these patients [see CLINICAL PHARMACOLOGY].