Pharmacokinetics of Clexane

The key pharmacokinetic properties of Clexane® [46] include:

• Rapid and complete absorption following subcutaneous injection
• Peak plasma anti-Xa activity reached between 3 and 5 hours after injection
• Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours after repeated dosing
• Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose

Clexane® is predominantly metabolised in the liver by desulfation or depolymerisation to lower molecular weight species and is eliminated renally [46]. A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. In patients with severe renal impairment (creatinine clearance < 30 ml/min), the AUC at steady state is significantly increased by an average of 65% after repeated, once daily subcutaneous doses of 4,000 IU (40 mg).

The elimination half-life may be prolonged in elderly patients although no dosage adjustment is necessary. A study of repeated, once daily subcutaneous doses of 150 IU/kg (1.5 mg/kg) in healthy volunteers suggests that no dosage adjustment is necessary in obese subjects (BMI 30–48 kg/m²) compared to non-obese subjects.

Clexane®, as detected by anti-Xa activity, does not cross the placental barrier during the second and third trimester of pregnancy [46].

No pharmacokinetic interactions were observed between Clexane® and thrombolytics when administered concomitantly [46].

There are special warnings and precautions for use in patients with renal impairment, the elderly, in obese patients and pregnant women. Please refer to section 4.4 of the SmPC for use of Clexane® in these patients.