Enoxaparin - Drug Monograph

Introduction

Enoxaparin is a low molecular weight heparin (LMWH) anticoagulant used for the prevention and treatment of thromboembolic disorders. As a derivative of unfractionated heparin, it offers several clinical advantages including predictable pharmacokinetics, subcutaneous bioavailability, and less frequent monitoring requirements. Enoxaparin has become a cornerstone therapy in the management of venous thromboembolism (VTE) and acute coronary syndromes.

Mechanism of Action

Enoxaparin exerts its anticoagulant effect by binding to antithrombin III (ATIII), significantly enhancing ATIII's ability to inactivate coagulation factor Xa and factor IIa (thrombin). The drug demonstrates a higher ratio of anti-factor Xa to anti-factor IIa activity (approximately 4:1) compared to unfractionated heparin. This preferential inhibition of factor Xa disrupts the coagulation cascade, preventing the conversion of prothrombin to thrombin and subsequent fibrin formation.

Indications

• Treatment of deep vein thrombosis (DVT) with or without pulmonary embolism (PE)
• Prophylaxis of DVT in patients undergoing hip or knee replacement surgery
• Prophylaxis of DVT in abdominal surgery patients at high risk for thromboembolic complications
• Prevention of ischemic complications in patients with unstable angina and non-Q-wave myocardial infarction
• Treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with percutaneous coronary intervention

Dosage and Administration

• Abdominal surgery: 40 mg SC once daily
• Hip or knee replacement: 30 mg SC every 12 hours or 40 mg SC once daily

• 1 mg/kg SC every 12 hours or 1.5 mg/kg SC once daily

• 1 mg/kg SC every 12 hours (with aspirin)

• 30 mg IV bolus followed by 1 mg/kg SC every 12 hours

• CrCl <30 mL/min: Dose reduction required (consult specific guidelines)
• Monitoring anti-Xa levels recommended in severe renal impairment

Pharmacokinetics

Contraindications

• Active major bleeding
• History of heparin-induced thrombocytopenia (HIT)
• Hypersensitivity to enoxaparin, heparin, or pork products
• Thrombocytopenia with positive in vitro tests for anti-platelet antibodies in the presence of enoxaparin

Warnings and Precautions

• Spinal/Epidural Hematoma Risk: Can occur with neuraxial anesthesia or spinal puncture, potentially resulting in paralysis
• Bleeding Risk: Increased in patients with congenital or acquired bleeding disorders, recent gastrointestinal ulceration, hemorrhagic stroke, or shortly after brain, spinal, or ophthalmological surgery
• Thrombocytopenia: Monitor platelet counts; discontinue if thrombosis develops
• Renal Impairment: Increased bleeding risk; requires dose adjustment
• Elderly Patients: Increased risk of bleeding due to reduced renal function
• Pregnancy: Category B; use with caution and only if clearly needed

Drug Interactions

• Oral Anticoagulants (warfarin): Increased risk of bleeding
• Antiplatelet Agents (aspirin, clopidogrel): Additive anticoagulant effect
• NSAIDs: Increased bleeding risk
• Thrombolytics: Enhanced anticoagulant effect
• Other Anticoagulants: Avoid concomitant use

Adverse Effects

• Injection site reactions (pain, erythema, ecchymosis)
• Bleeding complications
• Elevated liver enzymes
• Anemia

• Major bleeding episodes
• Heparin-induced thrombocytopenia (HIT)
• Spinal/epidural hematoma
• Hypersensitivity reactions
• Thrombocytopenia
• Skin necrosis

Monitoring Parameters

• Complete blood count with platelets (baseline and periodically)
• Signs and symptoms of bleeding
• Serum creatinine and renal function
• Anti-Xa levels (in specific populations: obesity, renal impairment, pregnancy)
• Monitor for signs of HIT: thrombocytopenia, new thrombosis, skin lesions
• Injection sites for reactions

Patient Education

• Report any signs of bleeding (unusual bruising, blood in urine/stool, bleeding gums)
• Inform all healthcare providers about enoxaparin use before any procedures
• Use soft toothbrush and electric razor to minimize bleeding risk
• Do not take NSAIDs or aspirin without medical supervision
• Proper injection technique: rotate sites, do not massage area after injection
• Recognize signs of blood clots: swelling, pain, redness in limbs; chest pain, shortness of breath
• Keep all follow-up appointments for monitoring

References

1. FDA Prescribing Information: Lovenox (enoxaparin sodium) injection 2. Kearon C, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016;149(2):315-352 3. Amsterdam EA, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes. Circulation 2014;130:e344-e426 4. Holbrook A, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2_suppl):e152S-e184S 5. Nutescu EA, et al. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 2009;43(6):1064-1083