HEPARIN SODIUM: Package Insert and Label Information

HEPARIN SODIUM- heparin sodium injection, solution
HF Acquisition Co LLC, DBA HealthFirst

HIGHLIGHTS OF PRESCRIBING INFORMATION


These highlights do not include all the information needed to use HEPARIN SODIUM INJECTION safely and effectively. See full prescribing information for HEPARIN SODIUM INJECTION.
HEPARIN SODIUM INJECTION, for intravenous or subcutaneous use
Initial U.S. Approval: 1984

INDICATIONS AND USAGE

Heparin Sodium Injection is an anticoagulant indicated for ( 1):

Prophylaxis and treatment of venous thrombosis and pulmonary embolism
Prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdomino-thoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease
Atrial fibrillation with embolization
Treatment of acute and chronic consumptive coagulopathies (disseminated intravascular coagulation)
Prevention of clotting in arterial and cardiac surgery
Prophylaxis and treatment of peripheral arterial embolism Use as an anticoagulant in blood transfusions, extracorporeal circulation and dialysis procedures

DOSAGE AND ADMINISTRATION

Recommended Adult Dosages:

Therapeutic Anticoagulant Effect with Full-Dose Heparin* (2.3)

HIGHLIGHTS
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DOSAGE FORMS AND STRENGTHS

Heparin Sodium: 5,000 USP Units/0.5 mL, Preservative free ( 3)
Heparin Sodium: 5,000 USP Units/1 mL ( 3)

CONTRAINDICATIONS

Severe thrombocytopenia ( 4)
When suitable blood coagulation tests, e.g., the whole blood clotting time, partial thromboplastin time, etc., cannot be performed at appropriate intervals ( 4)
An uncontrolled active bleeding state, except when this is due to disseminated intravascular coagulation ( 4)

WARNINGS AND PRECAUTIONS

Fatal Medication Errors: Confirm choice of correct strength prior to administration ( 5-5.1)
Hemorrhage: Fatal cases have occurred. Use caution in conditions with increased risk of hemorrhage ( 5-5.2)
HIT and HITTS: Monitor for signs and symptoms and discontinue if indicative of HIT and HITTS ( 5-5.3)
Benzyl Alcohol Toxicity: Do not use this product in neonates and infants ( 5-5.4)
Monitoring: Blood coagulation tests guide therapy for full-dose heparin ( 5-5.6)
Monitor platelet count and hematocrit in all patients receiving heparin ( 5-5.5, 5-5.6)

ADVERSE REACTIONS

Most common adverse reactions are: hemorrhage, thrombocytopenia, HIT and HITTS, local irritation, hypersensitivity reactions, and elevations of aminotransferase levels. ( 6-6.2)

To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Drugs that interfere with platelet aggregation: May induce bleeding. ( 7-7.2)

USE IN SPECIFIC POPULATIONS

Pregnancy: Preservative-free formulation recommended. Limited human data in pregnant women ( 8-8.1)
Lactation: Advise females not to breastfeed ( 8-8.2)
Pediatric Use: Use preservative-free formulation in neonates and infants ( 8-8.4)
Geriatric Use: A higher incidence of bleeding reported in patients, particularly women, over 60 years of age ( 8-8.5)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 4/2019

TABLE OF CONTENTS

FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
2.2 Laboratory Monitoring for Efficacy and Safety
2.3 Therapeutic Anticoagulant Effect With Full-Dose Heparin
2.4 Pediatric Use
2.5 Cardiovascular Surgery
2.6 Low-Dose Prophylaxis of Postoperative Thromboembolism
2.7 Blood Transfusion
2.8 Converting to Warfarin
2.9 Converting to Oral Anticoagulants other than Warfarin
2.10 Extracorporeal Dialysis
3DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Fatal Medication Errors
5.2 Hemorrhage
5.3 Heparin-induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis
5.4 Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative
5.5 Thrombocytopenia
5.6 Coagulation Testing and Monitoring
5.7 Heparin Resistance
5.8 Hypersensitivity
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Oral Anticoagulants
7.2 Platelet Inhibitors
7.3 Other Interactions
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION

*
Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS & USAGE

Heparin Sodium Injection is indicated for:

Prophylaxis and treatment of venous thrombosis and, pulmonary embolism;
Prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdomino-thoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease;
Atrial fibrillation with embolization;
Treatment of acute and chronic consumptive coagulopathies (disseminated intravascular coagulation);
Prevention of clotting in arterial and cardiac surgery;
Prophylaxis and treatment of peripheral arterial embolism; Anticoagulant use in blood transfusions, extracorporeal circulation, and dialysis procedures.

2 DOSAGE & ADMINISTRATION

2.1 Preparation for Administration

Confirm the choice of the correct Heparin Sodium Injection vial or cartridge prior to administration of the drug to a patient [see Warnings and Precautions (5.1)]. Heparin Sodium Injection, products must not be confused with “catheter lock flush” products. To lessen this risk for a cartridge, a red cautionary statement has been added to the cartridge and box/bin. Read the cautionary statement and confirm that you have selected the correct medication and strength.

When heparin is added to an infusion solution for continuous intravenous administration, invert the container repeatedly to ensure adequate mixing and prevent pooling of the heparin in the solution.

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and the seal is intact. Do not use if solution is discolored or contains a precipitate.

Administer Heparin Sodium Injection by intermittent intravenous injection, intravenous infusion, or deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal fat layer) injection. Do not administer Heparin Sodium Injection by intramuscular injection because of the risk of hematoma at the injection site [see Adverse Reactions (6)].

2.2 Laboratory Monitoring for Efficacy and Safety

Adjust the dosage of Heparin Sodium Injection according to the patient’s coagulation test results. Dosage is considered adequate when the activated partial thromboplastin time (aPTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. When initiating treatment with Heparin Sodium Injection by continuous intravenous infusion, determine the coagulation status (aPTT, INR, platelet count) at baseline and continue to follow aPTT approximately every 4 hours and then at appropriate intervals thereafter. When the drug is administered intermittently by intravenous injection, perform coagulation tests before each injection during the initiation of treatment and at appropriate intervals thereafter. After deep subcutaneous (intrafat) injections, tests for adequacy of dosage are best performed on samples drawn 4 to 6 hours after the injection.

Periodic platelet counts, and hematocrits are recommended during the entire course of heparin therapy, regardless of the route of administration.

2.3 Therapeutic Anticoagulant Effect With Full-Dose Heparin

The dosing recommendations in Table 1 are based on clinical experience. Although dosages must be adjusted for the individual patient according to the results of suitable laboratory tests, the following dosage schedules may be used as guidelines:

DOSAGE 1
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2.4 Pediatric Use

Use preservative-free Heparin Sodium Injection in neonates and infants [see Warnings and Precautions (5.4)].

There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. In general, the following dosage schedule may be used as a guideline in pediatric patients:

DOSAGE 2
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2.5 Cardiovascular Surgery

Patients undergoing total body perfusion for open-heart surgery should receive an initial dose of not less than 150 units of heparin sodium per kilogram of body weight. Frequently, a dose of 300 units per kilogram is used for procedures estimated to last less than 60 minutes, or 400 units per kilogram for those estimated to last longer than 60 minutes.

2.6 Low-Dose Prophylaxis of Postoperative Thromboembolism

The most widely used dosage has been 5,000 units 2 hours before surgery and 5,000 units every 8 to 12 hours thereafter for 7 days or until the patient is fully ambulatory, whichever is longer. Administer the heparin by deep subcutaneous injection (intrafat, i.e., above the iliac crest or abdominal fat layer, arm, or thigh) with a fine (25 to 26-gauge) needle to minimize tissue trauma.

2.7 Blood Transfusion

Add 450 to 600 USP units of Heparin Sodium per 100 mL of whole blood to prevent coagulation. Usually, 7,500 USP units of heparin sodium are added to 100 mL of 0.9% Sodium Chloride Injection, USP (or 75,000 USP units per 1,000 mL of 0.9% Sodium Chloride Injection, USP) and mixed; from this sterile solution, 6 mL to 8 mL are added per 100 mL of whole blood.

2.8 Converting to Warfarin

To ensure continuous anticoagulation when converting from Heparin Sodium Injection to warfarin, continue full heparin therapy for several days until the INR (prothrombin time) has reached a stable therapeutic range. Heparin therapy may then be discontinued without tapering [see Drug Interactions (7.1)].

2.9 Converting to Oral Anticoagulants other than Warfarin

For patients currently receiving intravenous heparin, stop intravenous infusion of Heparin Sodium immediately after administering the first dose of oral anticoagulant; or for intermittent intravenous administration of heparin sodium, start oral anticoagulant 0 to 2 hours before the time that the next dose of heparin was to have been administered.

2.10 Extracorporeal Dialysis

Follow equipment manufacturers’ operating directions carefully. A dose of 25 to 30 units/kg followed by an infusion rate of 1,500 to 2,000 units/hour is suggested based on pharmacodynamic data if specific manufacturer’s recommendations are not available.

3 DOSAGE FORMS & STRENGTHS

Heparin Sodium: 5,000 USP Units/0.5 mL, Preservative free
Heparin Sodium: 5,000 USP Units/1 mL

4 CONTRAINDICATIONS

The use of Heparin Sodium Injection is contraindicated in patients with the following conditions:

History of heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis [see Warnings and Precautions (5.3)]
Known hypersensitivity to heparin or pork products (e.g., anaphylactoid reactions) [see Adverse Reactions (6.2)]
In whom 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 uncontrolled active bleeding state [see Warnings and Precautions (5.4)], except when this is due to disseminated intravascular coagulation

5 WARNINGS AND PRECAUTIONS

5.1 Fatal Medication Errors

Do not use Heparin Sodium Injection as a “catheter lock flush” product. Heparin Sodium Injection is supplied in vials and sterile cartridges 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 and cartridges to confirm the correct product choice prior to administration of the drug.

5.2 Hemorrhage

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

Hemorrhage can occur at virtually any site in patients receiving heparin. Fatal hemorrhages have occurred. Adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy with heparin [see Adverse Reactions (6.2)]. A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age [see Clinical Pharmacology (12.3)]. An unexplained fall in hematocrit, fall in blood pressure or any other unexplained symptom 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.

5.3 Heparin-induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis

Heparin-Induced Thrombocytopenia (HIT) is a serious antibody-mediated reaction. 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 referred to as heparin-induced thrombocytopenia with 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, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. 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 Sodium should be evaluated for HIT or HITT.

5.4 Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative

Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including Heparin Sodium Injection multiple-dose vials. The “gasping syndrome” is characterized by central nervous system depression, metabolic acidosis, and gasping respirations.

The minimum amount of benzyl alcohol at which toxicity may occur is not known[see Use in Specific Populations(8.4)].

5.5 Thrombocytopenia

Thrombocytopenia in patients receiving heparin has been reported at frequencies 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 HITT, and, if necessary, administer an alternative anticoagulant [see Warnings and Precautions (5.3)].

5.6 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, discontinue heparin promptly [see Overdosage (10)]. Periodic platelet counts and hematocrits are recommended during the entire course of heparin therapy, regardless of the route of administration [see Dosage and Administration (2.2)].

5.7 Heparin Resistance

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.

5.8 Hypersensitivity

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations.

Because Heparin Sodium Injection is derived from animal tissue, it should be used with caution in patients with a history of allergy.

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