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ALERT: U.S. Boxed Warning

The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.

Medication Safety Issues

Sound-alike/look-alike issues:

Lovenox® may be confused with Lotronex®, Protonix®

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

International issues:

Lovenox® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic

Pronunciation

(ee noks a PA rin)

U.S. Brand Names

• Lovenox®

Index Terms

• Enoxaparin Sodium

Generic Available

No

Canadian Brand Names

• Enoxaparin Injection
• Lovenox®
• Lovenox® HP

Pharmacologic Category

• Low Molecular Weight Heparin

Pharmacologic Category Synonyms

• Anticoagulant, Low Molecular Weight Heparin
• LMWH

Use: Labeled Indications

Acute coronary syndromes: Unstable angina (UA), non-ST-segment elevation (NSTEMI), and ST-segment elevation myocardial infarction (STEMI)

DVT prophylaxis: Following hip or knee replacement surgery, abdominal surgery, or in medical patients with severely-restricted mobility during acute illness in patients at risk of thromboembolic complications

DVT treatment (acute): Inpatient treatment (patients with and without pulmonary embolism) and outpatient treatment (patients without pulmonary embolism)

Note: High-risk patients include those with one or more of the following risk factors: >40 years of age, obesity, general anesthesia lasting >30 minutes, malignancy, history of deep vein thrombosis or pulmonary embolism

Use: Unlabeled/Investigational

Prophylaxis and treatment of thromboembolism in children

Pregnancy Risk Factor

B

Pregnancy Considerations

There are no adequate and well-controlled studies using enoxaparin in pregnant women. Animal studies have not shown teratogenic or fetotoxic effects. Postmarketing reports include congenital abnormalities (cause and effect not established) and also fetal death when used in pregnant women. In addition, prosthetic valve thrombosis, including fatal cases, has been reported in pregnant women receiving enoxaparin as thromboprophylaxis. Multiple-dose vials contain benzyl alcohol; use caution in pregnant women.

Lactation

Excretion in breast milk unknown/use caution

Breast-Feeding Considerations

This drug has a high molecular weight that would minimize excretion in breast milk and is inactivated by the GI tract which further reduces the risk to the infant.

Contraindications

Hypersensitivity to enoxaparin, heparin, or any component of the formulation; thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of enoxaparin; hypersensitivity to pork products; active major bleeding; not for I.M. use

Warnings/Precautions

Boxed warnings:

• Neuraxial anesthesia: See “Other warnings/precautions” below.

Concerns related to adverse effects:

• Bleeding: Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding. Risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; severe uncontrolled hypertension; hemorrhagic stroke; or use shortly after brain, spinal, or ophthalmology surgery; in patient treated concomitantly with platelet inhibitors; recent GI bleeding; thrombocytopenia or platelet defects; severe liver disease; hypertensive or diabetic retinopathy; or in patients undergoing invasive procedures. Discontinue if bleeding occurs.

• Hyperkalemia: Monitor for hyperkalemia. Heparin can cause hyperkalemia by affecting aldosterone; similar reactions could occur with LMWHs.

• Thrombocytopenia: Rare cases of thrombocytopenia have occurred. Use with caution in patients with history of heparin-induced thrombocytopenia; monitor platelet count closely. Manufacturer recommends discontinuation of therapy if platelets are <100,000/mm³. Rare cases of thrombocytopenia with thrombosis have occurred. Use caution in patients with congenital or drug-induced thrombocytopenia or platelet defects.

Disease-related concerns:

• Prosthetic heart valves: Not recommended for thromboprophylaxis in patients with prosthetic heart valves (especially pregnant women).

• Renal impairment: Use with caution in patients with renal failure; dosage adjustment needed if Cl_cr <30 mL/minute.

Special populations:

• Elderly: Use with caution in the elderly; delayed elimination may occur. Dosage alteration/adjustment may be required (eg, omission of I.V. bolus in acute STEMI in patients ?75 years of age).

• Low weight patients: Risk of bleeding may be increased in women <45 kg and in men <57 kg.

• Pediatrics: Safety and efficacy have not been established in children.

Dosage form specific issues:

• Multidose vials: Contain benzyl alcohol and should not be used in pregnant women. In neonates, large amounts of benzyl alcohol (>100 mg/kg/day) have been associated with fatal toxicity (gasping syndrome).

Other warnings/precautions:

• Administration: Do not administer intramuscularly.

• Conversion to other products: Not to be used interchangeably (unit for unit) with heparin or any other low molecular weight heparins.

• Neuraxial anesthesia: [U.S. Boxed Warning]: Patients with recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) are at risk of spinal or epidural hematoma and subsequent paralysis. Consider risk versus benefit prior to neuraxial anesthesia; risk is increased by concomitant agents which may alter hemostasis, as well as traumatic or repeated epidural or spinal puncture. Patient should be observed closely for bleeding and signs and symptoms of neurological impairment if therapy is administered during or immediately following diagnostic lumbar puncture, epidural anesthesia, or spinal anesthesia.

Adverse Reactions

As with all anticoagulants, bleeding is the major adverse effect of enoxaparin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables. At the recommended doses, single injections of enoxaparin do not significantly influence platelet aggregation or affect global clotting time (ie, PT or aPTT).

1% to 10%:

Central nervous system: Fever (5% to 8%), confusion, pain

Dermatologic: Erythema, bruising

Gastrointestinal: Nausea (3%), diarrhea

Hematologic: Hemorrhage (major, <1% to 4%; includes cases of intracranial, retroperitoneal, or intraocular hemorrhage; incidence varies with indication/population), thrombocytopenia (moderate 1%; severe 0.1% - see note below), hypochromic anemia (2%)

Hepatic: ALT/AST increased

Local: Injection site hematoma (9%), local reactions (irritation, pain, ecchymosis, erythema)

<1% and/or postmarketing case reports (limited to important or life-threatening): Allergic reaction, anaphylactoid reaction, eczematous plaques, hematoma (see note on "Spinal or epidural hematomas" below), hyperlipidemia, hypertriglyceridemia, intracranial hemorrhage (up to 0.8%), erythematous pruritic patches, pruritus, purpura, retroperitoneal bleeding, skin necrosis, thrombocytosis, urticaria, vasculitis (cutaneous hypersensitive), vesicobullous rash

Notes:

Spinal or epidural hematomas: Can occur following neuraxial anesthesia or spinal puncture, resulting in paralysis. Risk is increased in patients with indwelling epidural catheters or concomitant use of other drugs affecting hemostasis. Prosthetic valve thrombosis, including fatal cases, has been reported in pregnant women receiving enoxaparin as thromboprophylaxis.

Thrombocytopenia with thrombosis: Cases of heparin-induced thrombocytopenia (some complicated by organ infarction, limb ischemia, or death) have been reported.

Drug Interactions

Anticoagulants: May enhance the anticoagulant effect of other Anticoagulants. Risk C: Monitor therapy

Antiplatelet Agents: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Drotrecogin Alfa: Heparin (Low Molecular Weight) may enhance the adverse/toxic effect of Drotrecogin Alfa. This is of most concern with therapeutic doses of LMW heparin. Bleeding may occur. Risk D: Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk D: Consider therapy modification

Ibritumomab: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Anticoagulants may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions

Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).

Storage

Store at 15°C to 25°C (59°F to 77°F); do not freeze.

Compatibility

Stable in NS; do not mix with other injections or infusions.

Mechanism of Action

Standard heparin consists of components with molecular weights ranging from 4000-30,000 daltons with a mean of 16,000 daltons. Heparin acts as an anticoagulant by enhancing the inhibition rate of clotting proteases by antithrombin III impairing normal hemostasis and inhibition of factor Xa. Low molecular weight heparins have a small effect on the activated partial thromboplastin time and strongly inhibit factor Xa. Enoxaparin is derived from porcine heparin that undergoes benzylation followed by alkaline depolymerization. The average molecular weight of enoxaparin is 4500 daltons which is distributed as (?20%) 2000 daltons (?68%) 2000-8000 daltons, and (?15%) >8000 daltons. Enoxaparin has a higher ratio of antifactor Xa to antifactor IIa activity than unfractionated heparin.

Pharmacodynamics/Kinetics

Onset of action: Peak effect: SubQ: Antifactor Xa and antithrombin (antifactor IIa): 3-5 hours

Duration: 40 mg dose: Antifactor Xa activity: ?12 hours

Metabolism: Hepatic, to lower molecular weight fragments (little activity)

Protein binding: Does not bind to heparin binding proteins

Half-life elimination, plasma: 2-4 times longer than standard heparin, independent of dose; based on anti-Xa activity: 4.5-7 hours

Excretion: Urine (40% of dose; 10% as active fragments)

Dosage

SubQ:

Infants and Children (unlabeled use):

Infants <2 months: Initial:

Prophylaxis: 0.75 mg/kg every 12 hours

Treatment: 1.5 mg/kg every 12 hours

Infants >2 months and Children ?18 years: Initial:

Prophylaxis: 0.5 mg/kg every 12 hours

Treatment: 1 mg/kg every 12 hours

Maintenance: See Dosage Titration table:

Adults:

DVT prophylaxis:

Hip replacement surgery:

Twice-daily dosing: 30 mg twice daily, with initial dose within 12-24 hours after surgery, and every 12 hours until risk of DVT has diminished or the patient is adequately anticoagulated on warfarin.

Once-daily dosing: 40 mg once daily, with initial dose within 9-15 hours before surgery, and daily until risk of DVT has diminished or the patient is adequately anticoagulated on warfarin.

Knee replacement surgery: 30 mg twice daily, with initial dose within 12-24 hours after surgery, and every 12 hours until risk of DVT has diminished (usually 7-10 days).

Abdominal surgery: 40 mg once daily, with initial dose given 2 hours prior to surgery; continue until risk of DVT has diminished (usual 7-10 days).

Medical patients with severely-restricted mobility during acute illness: 40 mg once daily; continue until risk of DVT has diminished

DVT treatment (acute): Note: Start warfarin within 72 hours and continue enoxaparin until INR is between 2.0 and 3.0 (usually 7 days).

Inpatient treatment (with or without pulmonary embolism): 1 mg/kg/dose every 12 hours or 1.5 mg/kg once daily.

Outpatient treatment (without pulmonary embolism): 1 mg/kg/dose every 12 hours.

ST-segment elevation myocardial infarction (STEMI):

Patients <75 years of age: Initial: 30 mg I.V. single bolus plus 1 mg/kg (maximum 100 mg for the first 2 doses only) SubQ every 12 hours. The first SubQ dose should be administered with the I.V. bolus. Maintenance: After first 2 doses, administer 1 mg/kg SubQ every 12 hours.

Patients ?75 years of age: Initial: SubQ: 0.75 mg/kg every 12 hours (Note: No I.V. bolus is administered in this population); a maximum dose of 75 mg is recommended for the first 2 doses. Maintenance: After first 2 doses, administer 0.75 mg/kg SubQ every 12 hours

Additional notes on STEMI treatment: Therapy was continued for 8 days or until hospital discharge; optimal duration not defined. Unless contraindicated, all patients received aspirin (75-325 mg daily) in clinical trials. In patients with STEMI receiving thrombolytics, initiate enoxaparin dosing between 15 minutes before and 30 minutes after fibrinolytic therapy. In patients undergoing PCI, if balloon inflation occurs <8 hours after the last SubQ enoxaparin dose, no additional dosing is needed. If balloon inflation occurs ?8 hours after last SubQ enoxaparin dose, a single I.V. dose of 0.3 mg/kg should be administered.

Unstable angina or non-ST-segment myocardial infarction (NSTEMI): 1 mg/kg every 12 hours in conjunction with oral aspirin therapy (100-325 mg once daily); continue until clinical stabilization (a minimum of at least 2 days)

Elderly: Refer to adult dosing. Increased incidence of bleeding with doses of 1.5 mg/kg/day or 1 mg/kg every 12 hours; injection-associated bleeding and serious adverse reactions are also increased in the elderly. Careful attention should be paid to elderly patients, particularly those <45 kg. Note: Dosage alteration/adjustment may be required.

Dosing adjustment in renal impairment: SubQ:

Cl_cr ?30 mL/minute: No specific adjustment recommended (per manufacturer); monitor closely for bleeding

Cl_cr <30 mL/minute:

DVT prophylaxis in abdominal surgery, hip replacement, knee replacement, or in medical patients during acute illness: 30 mg once daily

DVT treatment (inpatient or outpatient treatment in conjunction with warfarin): 1 mg/kg once daily

STEMI: Initial: I.V.: 30 mg as a single dose in patients <75 years of age; omit I.V. bolus in patients ?75 years of age. The first dose of the SubQ maintenance regimen is administered at the same time as the I.V. bolus. Maintenance: SubQ: 1 mg/kg every 24 hours in all patients

Unstable angina, NSTEMI: SubQ: 1 mg/kg once daily

Dialysis: Enoxaparin has not been FDA approved for use in dialysis patients. It's elimination is primarily via the renal route. Serious bleeding complications have been reported with use in patients who are dialysis dependent or have severe renal failure. LMWH administration at fixed doses without monitoring has greater unpredictable anticoagulant effects in patients with chronic kidney disease. If used, dosages should be reduced and anti-Xa activity frequently monitored, as accumulation may occur with repeated doses. Many clinicians would not use enoxaparin in this population especially without timely anti-Xa activity assay results.

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics.

Administration: I.V.

A single dose may be administered I.V. as part of treatment for ST-segment elevation myocardial infarction (STEMI) to patients <75 years of age; no I.V. bolus is given to patients ?75 years of age.

Administration: Other

Should be administered by deep SubQ injection to the left or right anterolateral and left or right posterolateral abdominal wall. To avoid loss of drug from the 30 mg and 40 mg syringes, do not expel the air bubble from the syringe prior to injection. In order to minimize bruising, do not rub injection site. An automatic injector (Lovenox EasyInjector™) is available with the 30 mg and 40 mg syringes to aid the patient with self-injections. Note: Enoxaparin is available in 100 mg/mL and 150 mg/mL concentrations.

Administration: I.V. Detail

pH: 5.5-7.5

Monitoring Parameters

Platelets, occult blood, and anti-Xa activity, if available; the monitoring of PT and/or aPTT is not necessary

Patient Education

Do not take any new prescription or OTC medications or herbal products during therapy without consulting prescriber. This drug can only be administered by injection. If self-administered, follow exact directions for injection and needle disposal. Do not make major changes to your diet unless recommended by prescriber. You may have a tendency to bleed easily while taking this drug (brush teeth with soft brush, use waxed dental floss, use electric razor, avoid scissors or sharp knives, and potentially harmful activities). Report chest pain; persistent constipation; persistent erection; unusual bleeding or bruising (bleeding gums, nosebleed, blood in urine, dark stool); pain in joints or back; or redness, swelling, burning, or pain at injection site. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.

Geriatric Considerations

No specific dosage adjustment recommendations for most indications, however, total clearance is lower and elimination is delayed in patients with renal failure. Adjustment may be necessary if renal impairment is present. In the treatment of STEMI, a lower dosage (0.75 mg/kg every 12 hours) and omission of the I.V. bolus, are recommended in patients ?75 years of age.

Over 2800 patients, ?65 years of age, have received enoxaparin sodium in pivotal clinical trials. The efficacy of enoxaparin injection in elderly (?65 years) was similar to that seen in younger patients (<65 years). The incidence of bleeding complications was similar between elderly and younger patients when 30 mg every 12 hours or 40 mg once daily doses of enoxaparin injection was administered at doses of 1.5 mg/kg/day or 1 mg/kg every 12 hours. The risk of enoxaparin injection associated bleeding increased with age. Serious adverse events increased with age for patients receiving enoxaparin injections. Other clinical experience (including postmarketing surveillance and literature reports) has not revealed additional differences in the safety of enoxaparin injection between elderly and younger patients. Careful attention to dosing intervals and concomitant medications (especially antiplatelet medications) is advised. Monitoring of elderly patients with low body weight (<45 kg) and those predisposed to decreased renal function should be considered.

Anesthesia and Critical Care Concerns/Other Considerations

Many critically-ill and surgical patients require preventative measures for venous thromboembolism. Low molecular weight heparins (LMWHs) compare favorably to unfractionated heparin in the prevention and treatment of venous thromboembolism. LMWHs are associated with less thrombocytopenia, compared to heparin, and do not require routine therapeutic monitoring.

Obesity/Renal Dysfunction: There is no consensus for adjusting/correcting the weight-based dosage of LMWH for patients who are morbidly obese. Monitoring of antifactor Xa concentration 4 hours after injection may be warranted. Patients who have a reduction in calculated creatinine clearance are at risk of accumulated anticoagulant effect when they are treated with certain LMWHs. All LMWHs may not behave the same in patients with renal dysfunction. Some clinicians monitor anti-Xa levels in patients with Cl_cr <30 mL/minute if assay results are readily available.

Cardiovascular Considerations

Low molecular weight heparins (LMWHs) compare favorably to unfractionated heparin (UFH) in the prevention and treatment of venous thromboembolism. LMWHs are associated with less thrombocytopenia, compared to heparin, and do not require routine therapeutic monitoring. In patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), the 2002 ACC/AHA guidelines recommend anticoagulation with subcutaneous LMWH or intravenous UFH be added to antiplatelet therapy with aspirin and/or clopidogrel. Enoxaparin is preferable to UFH as an anticoagulant unless CABG is planned within 24 hours (Class IIa recommendation; level of evidence: A). In patients with ST-segment elevation myocardial infarction, most studies are limited to small numbers of patients treated with dalteparin or enoxaparin. Control groups (placebo, UFH), dosing, primary endpoints (composite ones), and bleeding definitions vary. In general, the studies suggest equivalent or superior outcomes with these LMWHs and less major bleeding. Preliminary results of a larger trial comparing prehospital dosing of enoxaparin (30 mg I.V. bolus; 1 mg/kg SubQ twice daily for a maximum of 7 days) versus UFH in patients receiving tenecteplase suggests a higher incidence of major bleeding and intracranial hemorrhage in the enoxaparin group (Wallentin L, 2003). Almost all cases of intracranial hemorrhage were confined to patients >75 years of age. Another ongoing trial will address this safety issue. In the 2004 ACC/AHA guideline for patients with ST-elevation MI (STEMI), a low molecular weight heparin might be considered an acceptable alternative to unfractionated heparin for patients <75 years of age who are receiving fibrinolytic therapy. The patient must have reasonable renal function (serum creatinine <2.5 mg/dL in men and <2 mg/dL in women). Enoxaparin in combination with full-dose tenecteplase is the best studied regimen (Wallentin L, 2003).

Obesity/Renal Dysfunction: There is no consensus for adjusting/correcting the weight-based dosage of LMWH for patients who are morbidly obese. Monitoring of antifactor Xa concentration 4 hours after injection may be warranted. Patients who have a reduction in calculated creatinine clearance are at risk of accumulated anticoagulant effect when they are treated with certain LMWHs. All LMWHs may not behave the same in patients with renal dysfunction. Some clinicians monitor anti-Xa levels for patient with Cl_cr <30 mL/minute.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: As with all anticoagulants, bleeding is the major adverse effect of enoxaparin. Hemorrhage may occur at virtually any site; risk is dependent on multiple variables. At the recommended doses, single injections of enoxaparin do not significantly influence platelet aggregation or affect global clotting time (ie, PT or aPTT).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause confusion

Mental Health: Effects on Psychiatric Treatment

None reported

Nursing: Physical Assessment/Monitoring

Use caution in presence or history of conditions that increase risk of bleeding. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (especially anything that will impact coagulation or platelet aggregation). Note specific injection directions. Monitor results of laboratory tests, therapeutic effectiveness according to purpose for use, and adverse response (eg, bleeding, thrombosis). Teach patient possible side effects/appropriate interventions, and adverse symptoms to report.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution, as sodium [graduated prefilled syringe; preservative free]:

Lovenox®: 60 mg/0.6 mL (0.6 mL); 80 mg/0.8 mL (0.8 mL); 100 mg/mL (1 mL); 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

Injection, solution, as sodium [multidose vial]:

Lovenox®: 100 mg/mL (3 mL) [contains benzyl alcohol]

Injection, solution, as sodium [prefilled syringe; preservative free]:

Lovenox®: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL)

Pricing: U.S. (www.drugstore.com)

Solution (Lovenox)

30 mg/0.3 mL (3): $232.61

40 mg/0.4 mL (4): $321.27

60 mg/0.6 mL (6): $438.21

80 mg/0.8 mL (8): $555.99

100 mg/mL (10): $724.96

150 mg/mL (10): $1088.07

300 mg/3 mL (3): $229.98

References

Antman EM, Anbe SC, Alpert JS, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),” Circulation, 2004, 110(5):588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.

Antman EM, Cohen M, Radley D, et al, “Assessment of the Treatment Effect of Enoxaparin for Unstable Angina/Non-Q-Wave Myocardial Infarction. TIMI 11B-ESSENCE Meta-analysis,” Circulation, 1999, 100(15):1602-8.

Antman EM, McCabe CH, Gurfinkel EP, et al, “Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non-Q-Wave Myocardial Infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 11B Trial,” Circulation, 1999, 100(15):1593-601.

Antman EM, Morrow DA, McCabe CH, et al, “Enoxaparin Versus Unfractionated Heparin With Fibrinolysis for ST-Elevation Myocardial Infarction,” N Engl J Med, 2006, 354(14):1477-88.

Braunwald E, Antman EM, Beasley JW, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),” J Am Coll Cardiol, 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Cohen M, Bigonzi F, Le Louer V, et al, “One Year Follow-Up of the ESSENCE Trial (Enoxaparin Versus Heparin in Unstable Angina and Non-Q Wave Myocardial Infarction),” J Am Coll Cardiol, 1998, 31:79A.

Cohen M, Demers C, Gurfinkel EP, et al, “A Comparison of Low-Molecular-Weight Heparin With Unfractionated Heparin for Unstable Coronary Artery Disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group,” N Engl J Med, 1997, 337(7):447-52.

Farooq V, Hegarty J, Chandrasekar T, et al, “Serious Adverse Incidents With the Usage of Low Molecular Weight Heparins in Patients With Chronic Kidney Disease,” Am J Kidney Dis, 2004, 43(3):531-7.

Ferguson JJ, Califf RM, Antman EM, et al, “Enoxaparin vs. Unfractionated Heparin in High-Risk Patients With Non-ST-segment Elevation Acute Coronary Syndromes Managed With an Intended Early Invasive Strategy: Primary Results of the SYNERGY Randomized Trial,” JAMA, 2004, 292(1):45-54.

Fox KA, “Low Molecular Weight Heparin (Enoxaparin) in the Management of Unstable Angina: The ESSENCE Study. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events,” Heart, 1999, 82(Suppl 1):112-4.

Gerlach AT, Pickworth KK, Seth SK, et al, “Enoxaparin and Bleeding Complications: A Review in Patients With and Without Renal Insufficiency,” Pharmacotherapy, 2000, 20(7):771-5.

Hirsh J, Dalen J, and Guyatt G, et al, “The Sixth (2000) ACCP Guidelines for Antithrombotic Therapy for Prevention and Treatment of Thrombosis. American College of Chest Physicians,” Chest, 2001, 119(1 Suppl):346-7.

Monagle P, Michelson AD, Bovill E, et al, “Antithrombotic Therapy in Children,” Chest, 2001, 119:344S-70S.

Montalescot G, Philippe F, Ankri A, et al, “Early Increase of von Willebrand Factor Predicts Adverse Outcome in Unstable Coronary Artery Disease: Beneficial Effects of Enoxaparin. French Investigators of the ESSENCE Trial,” Circulation, 1998, 98(4):294-9.

Nagge J, Crowther M, and Hirsh J, “Is Impaired Renal Function a Contraindication to the Use of Low-Molecular Weight Heparin?” Arch Intern Med, 2002, 162(22):2605-9.

Polkinghorne KR, McMahon LP, and Becker GJ, “Pharmacokinetic Studies of Dalteparin (Fragmin), Enoxaparin (Clexane), and Danaparoid Sodium (Orgaran) in Stable Chronic Hemodialysis Patients,” Am J Kidney Dis, 2002, 40(5):990-5.

Reach L, Debure A, de Groc F, et al, “Anticoagulation With Enoxaparin 0.5 mg/kg in 630 Dialysis Sessions,” Haemostasis, 1994, 24(Suppl 1):280 [Abstract 281]

Simonneau G, Charbonnier B, Decousus H, et al, “Subcutaneous Low-Molecular-Weight Heparin Compared With Continuous Intravenous Unfractionated Heparin in the Treatment of Proximal Deep Vein Thrombosis,” Arch Intern Med, 1993, 153(13):1541-6.

Von Visger J and Magee C, “Low Molecular Weight Heparins in Renal Failure,” J Nephrol, 2003, 16(6):914-6.

Wallentin L, Goldstein P, Armstrong PW, et al, “Efficacy amd Safety of Tenecteplase in Combination With the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital Setting: The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS Randomized Trial in Acute Myocardial Infarction,” Circulation, 2003, 108(2): 135-42.

Wong GC, Giugliano RP, and Antman EM, “Use of Low-Molecular-Weight Heparins in the Management of Acute Coronary Artery Syndromes and Percutaneous Coronary Intervention,” JAMA, 2003, 289:331-42.

Zed PJ, Tisdale JE, and Borzak S, “Low-Molecular-Weight Heparins in the Management of Acute Coronary Syndromes,” Arch Intern Med, 1999, 159(16):1849-57.

International Brand Names

• Clexane (AR, AU, BE, CH, CZ, DE, ES, GB, HU, IE, IT, LU, MX, NL, PL)
• Clexane Forte (PL)
• Decipar (ES)
• Klexane (DK, FI, SE)
• Lovenox (AT, CH, FR, PT)
• Plaucina (ES)
• Trombenox (IT)

Lexi-Comp.com

Last full review/revision August 2008