Pronunciation: HEP-a-rin
Class: Anticoagulant

Trade Names

Heparin Sodium
- Injection 1,000 units/mL
- Injection 2,000 units/mL
- Injection 2,500 units/mL
- Injection 5,000 units/mL
- Injection 10,000 units/mL
- Injection 20,000 units/mL

Heparin Sodium in Dextrose 5%
- Injection 40 units/mL
- Injection 50 units/mL
- Injection 100 units/mL

Heparin Sodium in Sodium Chloride 0.45%
- Injection 50 units/mL
- Injection 100 units/mL

Heparin Sodium in Sodium Chloride 0.9%
- Injection 2 units/mL

Heparin I.V. Flush
- Lock flush injection 1 unit/mL
- Lock flush injection 10 units/mL
- Lock flush injection 100 units/mL

Monoject PreFill Advanced
- Lock flush injection 10 units/mL
- Lock flush injection 100 units/mL

Hepalean (Canada)
Hepalean-Lok (Canada)

Pharmacology

Inhibits reactions that lead to clotting of blood and formation of fibrin clots. Heparin acts at multiple sites in the normal coagulation system.

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Pharmacokinetics

Absorption

Heparin is not absorbed from GI; must be given IV or subcutaneously. T _max is 2 to 4 h (subcutaneous).

Metabolism

The liver and the reticuloendothelial system are the sites of biotransformation.

Elimination

The average half-life is 1.5 h (range, 1 to 6 h) and is dose dependent and nonlinear. Excreted in the urine, primarily as metabolites.

Hemodialysis

Heparin is not removed.

Onset

Onset is immediate (IV) and 20 to 60 min (subcutaneous).

Special Populations

Renal Function Impairment

The half-life may be increased.

Hepatic Function Impairment

The half-life may be increased or decreased.

Elderly

Plasma levels may be higher.

Indications and Usage

Prophylaxis and treatment of venous thrombosis and its extensions, pulmonary embolism (PE), peripheral arterial embolism, and atrial fibrillation with embolization; diagnosis and treatment of acute and chronic consumption coagulopathies (disseminated intravascular coagulation [DIC]); prevention of postoperative deep venous thrombosis (DVT) and PE. Also used to maintain catheter patency and as an anticoagulant in blood transfusions, extracorporeal circulation, dialysis, and laboratory samples.

Contraindications

Severe thrombocytopenia; uncontrolled bleeding (except because of DIC); patients in whom suitable blood coagulation tests cannot be performed; hypersensitivity to heparin or any other product ingredients; do not administer products containing benzyl alcohol as a perseverative to neonates, infants, pregnant women, or breast-feeding women; patients with hypersensitivity to corn products and bisulfites (may be contained in some heparin sodium in dextrose 5% products).

Dosage and Administration

Refer to the American College of Chest Physicians antithrombotic guidelines for more specific dosing, including weight-based dosing.

Adults Subcutaneous

5,000 units IV as initial dose followed by 8,000 to 10,000 units every 8 h or 15,000 to 20,000 units every 12 h.

Intermittent IV

10,000 units as initial dose followed by 5,000 to 10,000 units every 4 to 6 h.

IV infusion

5,000 units IV as initial dose followed by 20,000 to 40,000 units/day.

Children

IV infusion 50 units/kg as initial dose followed by 100 units/kg every 4 h or 20,000 unit/m ² per 24 h.

Blood Transfusion

Add 400 to 600 units per 100 mL of whole blood.

Catheter Patency
Adults

6 units/h (3 mL/h of the 2 units/mL formulation) has been found to be satisfactory.

Laboratory Samples

Add 70 to 150 units per 10 to 20 mL of whole blood.

Low-Dose Prophylaxis

Subcutaneous 5,000 units 2 h before surgery and every 8 to 12 h thereafter for 7 days or until patient is fully ambulatory, whichever is longer.

Surgery of Heart and Blood Vessels
Adults

At least 150 units/kg as initial dose. Frequently, 300 units/kg is given for procedures lasting less than 60 min. For procedures lasting longer than 60 min, 400 unit/kg is given.

General Advice

• Heparin manufactured after October 1, 2009 will be approximately 10% less potent than heparin manufactured prior to that date because of the revised USP heparin monograph. Use clinical judgement in determining the dose. More frequent monitoring of APTT or activated coagulation time may be required.
• Avoid IM administration.
• Subcutaneous administration should be deep, preferably into fatty layers of abdomen. Use a small-gauge needle to minimize tissue trauma. Rotate injection sites frequently.
• For IV infusion of concentrated heparin injection, dilute prescribed amount in sodium chloride 0.9% for injection, dextrose 5% in water, or another compatible solution. Use infusion pump to ensure accuracy.

Storage/Stability

Store between 68° and 77°F. Protect from freezing.

Drug Interactions

Activated protein C (eg, drotrecogin alfa [activated])

The risk of bleeding may be increased. Use with caution. Close clinical and laboratory monitoring are indicated.

Alteplase

The risk of serious bleeding may be increased. Use with caution in any condition for which serious bleeding constitutes an important hazard. Starting anticoagulant therapy within 24 h of treatment with IV-administered alteplase for the treatment of ischemic stroke is not recommended.

Antihistamines, digitalis, nicotine, nitroglycerin (IV), tetracycline

May partially counteract the anticoagulant action of heparin sodium. Monitor the coagulation status of the patient and adjust the heparin dose as needed.

Antithrombin

Pharmacologic effects of heparin may be increased. Close clinical and laboratory monitoring (APTT and/or anti-Xa) are indicated. Adjust the heparin as needed. Reduced doses of heparin are recommended when coadministered with antithrombin III.

Cephalosporins (eg, cefazolin, ceftriaxone)

Certain cephalosporins have caused coagulopathies; this might be additive with heparin, possibly increasing the risk of bleeding. Monitor for bleeding and coagulopathies. If an interaction is suspected, reduce the dose or discontinue one or both drugs.

Direct thrombin inhibitors (eg, desirudin)

The risk of bleeding may be increased. Concurrent use is not recommended.

Palifermin

Plasma concentrations and pharmacologic effects of palifermin may be increased. Coadministration should be avoided. In addition, rinse IV infusion lines maintained with heparin with normal saline before and after palifermin administration.

Penicillins, parenteral (eg, ampicillin, penicillin G)

Parenteral penicillins can produce alterations in platelet aggregation and coagulation tests. These effects might be additive with heparin, possibly increasing the risk of bleeding. Avoid excessive doses of parenteral penicillin during concurrent use of heparin. Closely monitor coagulation status and adjust the heparin dose as needed.

Platelet inhibitors (eg, aspirin, dextran, dipyridamole, hydroxychloroquine, NSAIDs [eg, ibuprofen, indomethacin], ticlopidine)

May cause increased risk of bleeding. Use with caution. In addition, heparin may reduce indomethacin efficacy when used to induce closure of a patent ductus arteriosus.

Streptokinase

Relative resistance to heparin anticoagulation following administration of streptokinase as a systemic thrombolytic agent may occur. Use more frequent monitoring of APTT to guide dosage adjustments.

Warfarin

Heparin may prolong the one-stage PT. In patients receiving warfarin, at least 5 h after the last IV heparin dose should elapse before blood is drawn if a valid PT is to be obtained.

Laboratory Test Interactions

Aminotransferase (AST and ALT)

Drug causes increased concentrations.

Adverse Reactions

Dermatologic

Cutaneous necrosis, itching and burning (especially on plantar side of foot), transient alopecia, urticaria.

Hematologic

Thrombocytopenia (0% to 30%); hemorrhage, including adrenal hemorrhage with resultant acute adrenal insufficiency, ovarian hemorrhage, or retroperitoneal hemorrhage.

Hypersensitivity

Allergic vasospastic reactions (including painful ischemia), anaphylactoid reactions, cyanotic limbs, hypersensitivity (eg, asthma, chills, fever, headache, lacrimation, nausea, rhinitis, shock urticaria, vomiting).

Lab Tests

Increased AST and ALT.

Local

Erythema, hematoma or ulceration following subcutaneous injection, local irritation, mild pain.

Musculoskeletal

Osteoporosis.

Miscellaneous

Priapism, rebound hyperlipidemia upon discontinuation.

Precautions

Pregnancy

Category C .

Lactation

Not excreted in breast milk. Compatible.

Children

Approved for use in children. However, according to some manufacturers, safety and effectiveness have not been established.

Elderly

Higher incidence of bleeding in women older than 60 y of age.

Hypersensitivity

Generalized hypersensitivity can occur. Reactions range from mild to severe.

Special Risk Patients

Use solutions containing sodium with caution, if at all, in patients with CHF, severe renal insufficiency, and edema with sodium retention. Use solutions containing dextrose with caution in patients with overt or known diabetes mellitus or carbohydrate intolerance.

Sulfite Sensitivity

Use caution in sulfite-sensitive patients; some preparations contain sulfites.

Benzyl alcohol sensitivity

Benzyl alcohol, used as preservative in some products, is associated with a fatal gasping syndrome in premature infants.

Fatal medication errors

Do not use heparin injection as a “catheter lock flush” product. Fatal hemorrhages have occurred because of product mix-ups.

Hemorrhage

Hemorrhage can occur at virtually any site. Use heparin with extreme caution in patients at increased risk of hemorrhage.

Heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis

Heparin-induced thrombocytopenia may progress to development of venous and arterial thromboses. Heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis can occur up to several weeks after discontinuation of heparin.

IM use

Avoid IM use because of local irritation, erythema, pain, hematoma, or ulceration.

Overdosage

Symptoms

Bleeding, easy bruising, hematuria, nosebleeds, petechiae, tarry stools.

Patient Information

• Caution patient to avoid IM injections.
• Advise patient to avoid activities that carry risk of injury.
• Instruct patient to use soft toothbrush and electric razor.
• Caution patient to avoid aspirin and aspirin-containing medications.
• Advise patient to report unusual bruising or bleeding (eg, bleeding gums, nosebleeds) or tarry stools to health care provider immediately.
• Instruct patient to inform health care provider and dentist of use of this medication before treatment or surgery.
• Inform patient of potential for hair loss. Explain that this effect may occur several months after heparin therapy is started. Reassure patient that if alopecia occurs, hair growth will return after drug has been discontinued.
• Advise patient to carry identification card or to wear a medication identification bracelet that indicates heparin therapy.
• Inform women that menstruation may be somewhat increased and prolonged. Usually this effect is not a contraindication to therapy if bleeding is not excessive and there is no underlying pathologic condition.
• Advise patient that smoking and drinking alcohol may alter response to heparin; therefore, these are not advised.
• Inform patient that abrupt withdrawal of heparin may precipitate increased coagulability.

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