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ALERT: U.S. Boxed Warning

The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.

Pronunciation

(ee noks a PA rin)

Generic Available (U.S.)

Yes: Injection solution (preservative free)

Index Terms

• Enoxaparin Sodium

Brand Names: U.S.

• Lovenox®

Brand Names: Canada

• 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-elevation (NSTEMI), and ST-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 who are at risk for 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

Prophylaxis and treatment of thromboembolism in children; anticoagulant bridge therapy during temporary interruption of vitamin K antagonist therapy in patients at high risk for thromboembolism; DVT prophylaxis following moderate-risk general surgery, major gynecologic surgery and following higher-risk general surgery for cancer; management of venous thromboembolism (VTE) during pregnancy; anticoagulant used during percutaneous coronary intervention (PCI)

Pregnancy Risk Factor

B

Pregnancy Considerations

Animal studies have not shown teratogenic or fetotoxic effects. Pregnancy itself increases the risk of thromboembolism. Pregnant women with a history of thromboembolic disease are at increased risk of maternal and fetal complications. Enoxaparin does not cross the placenta. Use may be recommended in pregnant women for the management of VTE. Monitoring antifactor Xa levels is recommended. Risk of adverse events may be increased in pregnant women with mechanical heart valves; use is controversial and has not been adequately studied. Postmarketing reports include congenital abnormalities (cause and effect not established) and also fetal death when used in pregnant women. 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; history of hemorrhagic stroke; or use shortly after brain, spinal, or ophthalmic surgery; in patients 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; can cause hyperkalemia possibly by suppressing aldosterone production. Most commonly occurs in patients with risk factors for the development of hyperkalemia (eg, renal dysfunction, concomitant use of potassium-sparing diuretics or potassium supplements, hematoma in body tissues).

• Thrombocytopenia: Rare cases of thrombocytopenia have occurred. Use with caution in patients with history of heparin-induced thrombocytopenia; monitor platelet count closely. Discontinue therapy and consider alternative treatment if platelets are <100,000/mm³ and/or thrombosis develops. 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: Cannot be recommended for long-term thromboprophylaxis in patients with prosthetic heart valves (especially pregnant women) due to insufficient evidence.

• 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.

• Obesity: There is no consensus for adjusting/correcting the weight-based dosage of LMWH for patients who are morbidly obese (BMI ≥40 kg/m²). Anti-Xa levels are increased to appropriate levels when enoxaparin is dosed on actual body weight in obese patients weighing up to 144 kg (Sanderink, 2002). Monitoring of anti-Xa levels 4 hours after the dose may be warranted. For patients undergoing inpatient bariatric surgery, the American College of Chest Physicians Practice Guidelines suggest using a higher thromboprophylaxis dose of LMWH for obese patients (Geerts, 2008).

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]: Spinal or epidural hematomas, including subsequent paralysis, may occur with recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture in patients anticoagulated with LMWH or heparinoids. Consider risk versus benefit prior to spinal procedures; risk is increased by the use of concomitant agents which may alter hemostasis, the use of indwelling epidural catheters for analgesia, a history of spinal deformity or spinal surgery, as well as a history of traumatic or repeated epidural or spinal punctures. 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), anemia (<2%)

Hepatic: ALT, increased, AST increased

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

Renal: Hematuria (<2%)

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

Note:

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.

Metabolism/Transport Effects

None known.

Drug Interactions

5-ASA Derivatives: May enhance the adverse/toxic effect of Heparin (Low Molecular Weight). Specifically, the risk for bleeding/bruising may be increased. Risk C: Monitor therapy

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

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

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

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Drotrecogin Alfa (Activated): Heparin (Low Molecular Weight) may enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Potential benefits of therapeutic doses of LMW heparins should be weighed against an increased risk of bleeding in patients who receive drotrecogin alfa. In patients receiving prophylactic LMW heparin doses consider continuing this during drotrecogin. 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

Pentoxifylline: May enhance the anticoagulant effect of Heparin (Low Molecular Weight). 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

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Risk X: Avoid combination

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

Thrombolytic Agents: 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 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze.

Compatibility

Stable in D₅W, 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

Distribution: 4.3 L (based on antifactor Xa activity)

Protein binding: Does not bind to heparin binding proteins

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

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

One mg of enoxaparin is equal to 100 int. units of anti-Xa activity (World Health Organization First International Low Molecular Weight Heparin Reference Standard).

Infants and Children (unlabeled use; Monagle, 2008): SubQ:

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:

SubQ:

DVT prophylaxis: Note: In morbidly obese patients (BMI ≥40 kg/m²), increasing the prophylactic dose by 30% may be appropriate for some indications (Nutescu, 2009). For bariatric surgery, dose increases may be >30% based on clinical trial data. SubQ:

Hip replacement surgery:

Twice-daily dosing: 30 mg every 12 hours, with initial dose within 12-24 hours after surgery, and every 12 hours for at least 10 days or 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 for at least 10 days (or up to 35 days postoperatively) or until risk of DVT has diminished or the patient is adequately anticoagulated on warfarin.

Knee replacement surgery: 30 mg every 12 hours, with initial dose within 12-24 hours after surgery, and every 12 hours for at least 10 days or until risk of DVT has diminished or the patient is adequately anticoagulated on warfarin.

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

Bariatric surgery: Roux-en-Y gastric bypass: Appropriate dosing strategies have not been clearly defined (Borkgren-Okonek, 2008; Scholten, 2002):

BMI ≤50 kg/m²: 40 mg every 12 hours

BMI >50 kg/m²: 60 mg every 12 hours

Note: Bariatric surgery guidelines suggest initiation 30-120 minutes before surgery and postoperatively until patient is fully mobile (Mechanick, 2009). Alternatively, limiting administration to the postoperative period may reduce perioperative bleeding.

Medical patients with severely-restricted mobility during acute illness: 40 mg once daily; continue until risk of DVT has diminished (usually 6-11 days).

DVT treatment (acute): Note: Start warfarin on the first treatment day and continue enoxaparin until INR is between 2 and 3 (usually 5-7 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.

Obesity: Use actual body weight to calculate dose; dose capping not recommended; use of twice daily dosing preferred (Nutescu, 2009).

ST-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

Obesity: Use weight-based dosing; a maximum dose of 100 mg is recommended for the first 2 doses (Nutescu, 2009)

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 8-12 hours after last SubQ enoxaparin dose, a single I.V. dose of 0.3 mg/kg should be administered (Hirsh, 2008; King, 2007).

Unstable angina or non-ST-elevation 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)

Obesity: Use actual body weight to calculate dose; dose capping not recommended (Nutescu, 2009)

I.V.: Percutaneous coronary intervention (PCI), adjunctive therapy (unlabeled use): In patients treated with multiple doses of enoxaparin undergoing PCI, if PCI occurs within 8 hours after the last SubQ enoxaparin dose, no additional dosing is needed. If PCI occurs 8-12 hours after the last SubQ enoxaparin dose or the patient received only 1 therapeutic SubQ dose (eg, 1 mg/kg), a single I.V. dose of 0.3 mg/kg should be administered. If PCI occurs >12 hours after the last SubQ dose, it is prudent to use an established anticoagulation regimen (eg, unfractionated heparin or bivalirudin) (Levine, 2011).

If patient has not received prior anticoagulant therapy: 0.5-0.75 mg/kg bolus dose (Levine, 2011)

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:

<75 years: Initial: I.V.: 30 mg as a single dose with the first dose of the SubQ maintenance regimen administered at the same time as the I.V. bolus; Maintenance: SubQ: 1 mg/kg every 24 hours

≥75 years of age: Omit I.V. bolus; Maintenance: SubQ: 1 mg/kg every 24 hours

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 levels frequently monitored, as accumulation may occur with repeated doses. Many clinicians would not use enoxaparin in this population especially without timely anti-Xa levels.

Hemodialysis: Supplemental dose is not necessary.

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

Administration: I.M.

Do not administer I.M.

Administration: I.V.

May be administered I.V. as part of treatment for ST-elevation myocardial infarction (STEMI) only in patients <75 years of age or during PCI. The manufacturer recommends using the multiple-dose vial to prepare I.V. doses. Do not mix or coadminister with other medications.

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.

To convert from I.V. unfractionated heparin (UFH) infusion to SubQ enoxaparin (Nutescu, 2007): Calculate specific dose for enoxaparin based on indication, discontinue UFH and begin enoxaparin within 1 hour.

To convert from SubQ enoxaparin to I.V. UFH infusion (Nutescu, 2007): Discontinue enoxaparin, calculate specific dose for I.V. UFH infusion based on indication, omit heparin bolus/loading dose:

Converting from SubQ enoxaparin dosed every 12 hours: Start I.V. UFH infusion 10-11 hours after last dose of enoxaparin

Converting from SubQ enoxaparin dosed every 24 hours: Start I.V. UFH infusion 22-23 hours after last dose of enoxaparin

Administration: I.V. Detail

pH: 5.5-7.5

Monitoring Parameters

Platelets, occult blood, anti-Xa levels, serum creatinine; monitoring of PT and/or aPTT is not necessary. Routine monitoring of anti-Xa levels is not required, but has been utilized in patients with obesity and/or renal insufficiency. Monitoring anti-Xa levels is recommended in pregnant women receiving therapeutic doses of enoxaparin (Hirsh, 2008). For patients >190 kg, if anti-Xa monitoring is available, adjusting dose based on anti-Xa levels is recommended; if anti-Xa monitoring is unavailable, reduce dose if bleeding occurs (Nutescu, 2009).

Reference Range

The following therapeutic ranges for anti-Xa levels have been suggested, but have not been validated in a controlled trial. Anti-Xa level measured 4 hours postdose.

DVT treatment (every-12-hour dosing): 0.6-1 units/mL

DVT treatment (once-daily dosing): 1-2 units/mL

Patient Education

This drug can only be administered by injection. If self-administered, follow exact directions for injection and needle disposal. You may have a tendency to bleed easily while taking this drug. Report unusual bleeding or bruising (bleeding gums, nosebleed, blood in urine, dark stool); pain in joints or back; redness, swelling, burning, or pain at injection site; severe headache or confusion; or any rash.

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.

In 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 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

Evidence-Based Information: The American College of Chest Physicians Evidence Based Clinical Practice Guidelines (Geerts, 2008) recommend routine assessment for venous thromboembolism (VTE) risk and routine thromboprophylaxis in most critically ill patients (Grade 1A). For critically ill patients at a moderate risk (medically ill or postoperative) for VTE, they recommend using LMWH or low-dose unfractionated heparin (Grade 1A). For critically ill patients at a high risk (major trauma or orthopedic surgery) for VTE, they recommend LMWH (Grade 1A). If bleeding risk prohibits the use of pharmacologic thromboprophylaxis, mechanical thromboprophylaxis is recommended until risk decreases (Grade 1A).

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-elevation myocardial infarction (UA/NSTEMI), the 2011 ACCF/AHA guidelines recommend anticoagulation with subcutaneous enoxaparin or intravenous UFH be added to antiplatelet therapy (eg, aspirin and/or clopidogrel) (Class I recommendation; level of evidence: A). Enoxaparin (or fondaparinux) is preferable to UFH as an anticoagulant unless CABG is planned within 24 hours (Class IIa recommendation; level of evidence: B). In patients with ST-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, 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, 2003).

Obesity/Renal Dysfunction: The 2008 Chest guidelines recommend that dosing (prophylaxis or treatment) in patients with obesity should be weight-based (actual body weight) and not a fixed-dose regimen (Grade 2C; Hirsh, 2008). Nutescu, et al (2009) have recommended that LMWH doses should be increased (eg, by ~30%) in patients with morbid obesity (BMI ≥40 kg/m²) when used for VTE prophylaxis and should be weight based (actual body weight) without dose capping when used for VTE treatment. LMWH doses should also be weight based (actual body weight) when used for NSTEMI or STEMI; however, refer to the manufacturer's recommendations regarding maximum dose for these indications.

Patients who have a reduced calculated creatinine clearance are at risk of accumulated anticoagulant effect when they are treated with LMWHs therefore dose adjustments may be necessary depending on the degree of renal insufficiency. Some LMWHs have a greater dependency on the kidneys for elimination (eg, enoxaparin) compared to others (eg, dalteparin or tinzaparin). Of note, the 2008 Chest guidelines recommend that patients with Cl_cr <30 mL/minute who require therapeutic anticoagulation be treated with unfractionated heparin instead of LMWH (Grade 2C; Hirsh, 2008).

Anti-Xa monitoring: In patients weighing >190 kg (or BMI >40 kg/m²), monitoring of anti-Xa concentrations 4 hours after injection may be considered if the assay is available. In general, monitoring anti-Xa levels is not necessary in patients who are clinically stable, uncomplicated, or those weighing <190 kg. For patients with Cl_cr <30 mL/minute, may consider monitoring anti-Xa levels when the assay (ie, chromogenic method with calibration curve based on the LMWH) is available. May also monitor trough anti-Xa levels to determine if accumulation is occurring in patients with renal impairment (Nutescu, 2009).

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Bleeding is the major adverse effect of enoxaparin. See Effects on Bleeding.

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. Monitor for bleeding.

Dosage Forms

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

Injection, solution, as sodium:

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

Injection, solution, as sodium [preservative free]: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 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)

Lovenox®: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 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) [prefilled syringe]

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

Solution (Enoxaparin Sodium)

30 mg/0.3 mL (0.3): $23.99

40 mg/0.4 mL (0.4): $32.99

60 mg/0.6 mL (0.6): $46.99

80 mg/0.8 mL (0.8): $63.99

100 mg/mL (1): $79.99

120 mg/0.8 mL (0.8): $95.99

150 mg/mL (1): $119.99

Solution (Lovenox)

30 mg/0.3 mL (3): $259.99

40 mg/0.4 mL (4): $354.23

80 mg/0.8 mL (8): $649.98

100 mg/mL (10): $815.98

150 mg/mL (10): $1250.00

References

Anderson JL, Adams CD, Antman EM, et al, "2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines," Circulation, 2011, 123(18):e426-579.

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.

Antman EM, Anbe DT, Armstrong PW, et al,“ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction),” Circulation, 2004, 110(9):e82-292.

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International Brand Names

• Clenox (CO, PE)
• Clexa (PH)
• Clexane (AR, AU, BB, BE, BF, BG, BJ, BM, BR, BS, CH, CI, CL, CN, CO, CR, CZ, DE, DO, EC, EE, ES, ET, GB, GH, GM, GN, GR, GT, GY, HK, HN, HU, IE, IL, IN, IT, JM, KE, KP, LR, LU, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NZ, PA, PE, PH, PK, PL, PR, PY, RU, SC, SD, SG, SL, SN, SV, TH, TN, TR, TT, TW, TZ, UG, UY, VE, ZM, ZW)
• Clexane Forte (AU, IL)
• Decipar (ES)
• Klexane (DK, FI, NO, SE)
• Lomoh-40 (PH)
• Lomoh-60 (PH)
• Lovenox (AT, FR, ID, PT)
• Microparin (DO, GT, SV)
• Plaucina (ES)

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Last full review/revision February 2012

Content last modified February 2012