Lovenox - Drug Monograph

Introduction

Lovenox (enoxaparin sodium) is a low molecular weight heparin (LMWH) anticoagulant used for the prevention and treatment of thromboembolic disorders. It represents a significant advancement over unfractionated heparin with more predictable pharmacokinetics, improved bioavailability, and simplified dosing without requiring routine laboratory monitoring in most clinical scenarios.

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 exhibits 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 in the coagulation cascade prevents the conversion of prothrombin to thrombin and subsequent fibrin formation.

Indications

FDA-approved indications include:

• Prophylaxis of deep vein thrombosis (DVT) following hip or knee replacement surgery
• Prophylaxis of DVT following abdominal surgery
• Prophylaxis of DVT in medical patients at risk for thromboembolic complications
• Treatment of acute DVT with or without pulmonary embolism
• Treatment of acute ST-elevation myocardial infarction (STEMI)
• Prevention of ischemic complications of unstable angina and non-Q-wave myocardial infarction

Dosage and Administration

• DVT prophylaxis: 30 mg SC twice daily or 40 mg SC once daily
• DVT treatment: 1 mg/kg SC every 12 hours or 1.5 mg/kg SC once daily
• STEMI: Single IV bolus of 30 mg followed by 1 mg/kg SC every 12 hours

• Renal impairment (CrCl <30 mL/min): Dose reduction required
• Obesity: Use total body weight for dosing
• Pregnancy: No dosage adjustment required
• Pediatric patients: Limited data available; consult specialized references

Pharmacokinetics

• Absorption: Bioavailability approximately 90% following SC injection
• Distribution: Volume of distribution approximately 4-6 L; primarily distributes in blood
• Metabolism: Primarily hepatic via desulfation and depolymerization
• Elimination: Renal elimination with half-life of 4.5-7 hours
• Onset: Peak anti-Xa activity occurs 3-5 hours after SC administration

Contraindications

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

Warnings and Precautions

• Spinal/Epidural hematoma risk: Can occur with neuraxial anesthesia or spinal puncture
• Increased bleeding risk: Monitor for signs of bleeding
• Thrombocytopenia: Monitor platelet counts; discontinue if HIT suspected
• Renal impairment: Increased risk of bleeding; requires dose adjustment
• Elderly patients: Increased risk of bleeding complications
• Pregnancy Category B: Use cautiously during pregnancy

Drug Interactions

• Anticoagulants/antiplatelets: Increased bleeding risk with warfarin, aspirin, NSAIDs, clopidogrel
• Thrombolytics: Significant increase in bleeding risk
• SSRIs/SNRIs: Potential increased bleeding risk
• Herbal supplements: Garlic, ginger, ginkgo, and ginseng may increase bleeding risk

Adverse Effects

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

• Major bleeding events
• Heparin-induced thrombocytopenia
• Spinal/epidural hematoma
• Hypersensitivity reactions
• Skin necrosis at injection sites

Monitoring Parameters

• Routine: Signs and symptoms of bleeding
• Laboratory:

- Complete blood count (including platelets) - Serum creatinine (for renal function assessment) - Liver function tests - Anti-Xa levels (in special populations: obesity, renal impairment, pregnancy)

• Clinical: Injection sites for reactions, neurological assessment in patients with neuraxial anesthesia

Patient Education

• Proper injection technique and site rotation
• Signs of bleeding to report immediately (unusual bruising, bleeding gums, dark urine/stool)
• Importance of compliance with prescribed regimen
• Need to inform all healthcare providers of Lovenox use
• Avoidance of OTC medications without healthcare provider approval
• Recognition of signs of allergic reaction
• Use of soft-bristle toothbrush and electric razor to minimize bleeding risk

References

1. FDA Prescribing Information: Lovenox (enoxaparin sodium) injection 2. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. 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. 3. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):141S-159S. 4. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S-e43S. 5. van Dongen CJ, van den Belt AG, Prins MH, Lensing AW. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2004;(4):CD001100.