Heparin Sodium: Package Insert and Label Information

HEPARIN SODIUM- heparin sodium injection, solution
Hospira, Inc.

1 INDICATIONS AND USAGE

Heparin sodium is indicated for:

Prophylaxis and treatment of venous thrombosis and pulmonary embolism;
Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation;
Treatment of acute and chronic consumption 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 AND ADMINISTRATION

2.1 Preparation for Administration

Confirm the selection of the correct formulation and strength prior to administration of the drug. Do not use Heparin Sodium in 0.45% Sodium Chloride Injection as a “catheter lock flush” product.

Administer this product by intravenous infusion.

Do not admix with other drugs.

Do not use flexible container in series connections.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

2.2 Laboratory Monitoring for Efficacy and Safety

Adjust the dosage of heparin sodium according to the patient’s coagulation test results. When heparin is given by continuous intravenous infusion, determine the coagulation time approximately every 4 hours in the early stages of treatment. When the drug is administered intermittently by intravenous injection, perform coagulation tests before each injection during the early stages of treatment and at appropriate intervals thereafter. Dosage is considered adequate when the activated partial thromboplastin time (APTT) is 1.5 to 2 times the normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value.

Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy.

2.3 Therapeutic Anticoagulant Effect with Full-Dose Heparin

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

Table 1: Recommended Adult Full-Dose Heparin Regimens for Therapeutic Anticoagulant Effect
*
Based on 150 lb. (68 kg) patient.

Method of Administration

Frequency

Recommended Dose *

IntermittentIntravenous Injection

Initial Dose

10,000 Units

Every 4 to 6 hours

5,000 – 10,000 Units

ContinuousIntravenous Infusion

Initial Dose

5,000 Units by IV injection

Continuous

20,000 – 40,000 Units/24 hours

2.4 Pediatric Use

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:

Initial Dose 75 to 100 units/kg (IV bolus over 10 minutes)
Maintenance Dose Infants: 25 to 30 units/kg/hour;
Infants < 2 months have the highest requirements (average 28 units/kg/hour)
Children > 1 year of age: 18 to 20 units/kg/hour;
Older children may require less heparin, similar to weight-adjusted adult dosage
Monitoring Adjust heparin to maintain a PTT of 60 to 85 seconds, assuming this reflects an anti-Factor Xa level of 0.35 to 0.70.

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 Converting to Warfarin

To ensure continuous anticoagulation when converting from HEPARIN SODIUM 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 (7.4) ].

2.7 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.

2.8 Extracorporeal Dialysis

Follow equipment manufacturer’s 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 manufacturers’ recommendations are not available.

3 DOSAGE FORMS AND STRENGTHS

HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION is available as:

Injection: 100 USP Units/mL in 0.45% Sodium Chloride clear solution (25,000 USP Units/250 mL) in single-dose plastic container
Injection: 50 USP Units/mL in 0.45% Sodium Chloride clear solution (12,500 USP Units/250 mL) in single-dose plastic container
Injection: 50 USP Units/mL in 0.45% Sodium Chloride clear solution (25,000 USP Units/500 mL) in single-dose plastic container

4 CONTRAINDICATIONS

The use of HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION is contraindicated in patients:

With history of heparin-induced thrombocytopenia (HIT) (With or Without Thrombosis) [see Warnings and Precautions (5.3) ]
With a known hypersensitivity to heparin or pork products (e.g., anaphylactoid reactions) [see Adverse Reactions (6.1) ]
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)

5 WARNINGS AND PRECAUTIONS

5.1 Fatal Medication Errors

Do not use this product as a “catheter lock flush” 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.

5.2 Hemorrhage

Hemorrhage, including fatal events, has occurred in patients receiving HEPARIN SODIUM. 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. Adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy with heparin [see Adverse Reactions (6.1) ]. 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 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.

5.3 Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis)

HIT is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition known 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, 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/mm 3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT, and, if necessary, administer an alternative anticoagulant.

HIT 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.

5.4 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 (5.3) ].

5.5 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 (10) ]. Periodic platelet counts, hematocrits are recommended during the entire course of heparin therapy [see Dosage and Administration (2.2) ].

5.6 Heparin Resistance

Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer and 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.

5.7 Hypersensitivity

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations [see Adverse Reactions (6) ]. 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.

6 ADVERSE REACTIONS

The following serious 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 [see Warnings and Precautions (5.7) ]

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.

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:
Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred with heparin therapy, including fatal cases. Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term anticoagulant therapy.
Retroperitoneal hemorrhage.
Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) and Thrombocytopenia: [see Warnings and Precautions (5.3 and 5.4)]
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) ].
Elevations of serum aminotransferases – Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in patients 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.
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