Enoxaparin Sodium (LMWH)

Mechanism

Mechanism of Action

Enoxaparin is a Low Molecular Weight Heparin (LMWH) produced by alkaline depolymerization of the benzyl ester of heparin mucosa from pig intestine. The average molecular weight is approximately 4,500 Da.

Having shorter chains than UFH, enoxaparin largely lacks the chain length necessary to simultaneously bind antithrombin and thrombin (bridging effect). Therefore, it exhibits a high selectivity for the inhibition of Factor Xa over Factor IIa (Thrombin), with an anti-Xa/anti-IIa activity ratio of approximately 4:1.

Pharmacokinetics

Pharmacokinetics

• Route of administration: Deep subcutaneous injection into abdominal fat; intravenous administration for the initial STEMI bolus when indicated.
• Bioavailability (F): Approximately 100% bioavailability after subcutaneous injection, supporting a predictable response without routine anti-Xa monitoring in most patients.
• Distribution: Lower binding affinity for acute-phase proteins and endothelial cells than unfractionated heparin. Apparent volume of distribution about 4.3 L.
• Metabolism and Excretion: Partly metabolized hepatically through desulfation and depolymerization into smaller fragments. Active fragments are eliminated predominantly renal (clearance of approximately 30% of the dose).
• Half-life (t_1/2): The anti-Xa-based half-life is approximately 4.5 hours after a single subcutaneous dose and 7 hours after repeated dosing. Renal impairment increases exposure and may require dose adjustment; 7 hours is not a specific renal-impairment value.

Indicators and dose

Indications

• VTE prophylaxis in orthopedic or general surgery and in medical patients acutely ill due to immobilization.
• Treatment of stable DVT and PE.
• Treatment of AMI with ST segment elevation (STEMI) or without elevation (NSTEMI).
• Prevention of coagulation in the extracorporeal circulation circuit during hemodialysis.

Dosing and Precision Adjustment

Black Box Warning (FDA): Neuroaxial Anesthesia

When a lumbar puncture or spinal/epidural anesthesia is planned, the use of LMWH significantly increases the risk of developing a spinal or epidural hematoma, which can lead to acute-onset irreversible neurological paralysis. A safety interval of at least 10 - 12 hours for prophylactic doses and 24 hours for therapeutic doses must be strictly observed between the last injection of enoxaparin and the insertion or removal of the neuraxial catheter. Enoxaparin should not be restarted until a minimum of 4 hours after the procedure.

Pregnancy and Breastfeeding

FDA Category B. It is the gold standard in the treatment and prophylaxis of thrombosis during pregnancy. It does not cross the placental barrier and has no reported teratogenic effects. Compatible with breastfeeding; excretion in breast milk is negligible and it is inactivated orally in the digestive tract of the infant.

Security

Contraindications

Absolute

• Hypersensitivity to enoxaparin or other LMWHs.
• Clinically significant active bleeding.
• History of antibody-mediated HIT induced by LMWH or UFH.
• Severe active coagulation disorders.

Relative

• End-stage renal failure (creatinine clearance < 15 mL/min if not on dialysis).
• Simultaneous use with neuraxial anesthesia (epidural/spinal) due to risk of spinal hematoma.
• Severe compensated liver disease.

Adverse effects (ADRs)

• Hemorrhage: Main adverse effect, typically less than with UFH, but with risk of retroperitoneal or injection site hematomas.
• Thrombocytopenia (HIT type II): Substantially lower risk than with UFH (< 1%), but possible due to cross-reactivity of antibodies against heparin-FP4 complexes.
• Elevation of transaminases: Reversible increase in AST and ALT (up to 3 times the upper limit of normal) without actual hepatocellular damage or elevation of bilirubin.
• Local reactions: Pain, erythema, ecchymosis and, rarely, skin necrosis at the injection site.

Interactions

Increased bleeding risk with the concomitant use of antiplatelet agents, oral anticoagulants, thrombolytics, NSAIDs and high-dose systemic glucocorticoids. Protamine sulfate partially neutralizes anti-Xa activity (maximum 60% neutralization) and almost completely neutralizes anti-IIa activity.