Since LMWHs are eliminated predominantly via the kidneys, drug accumulation risk exists in patients with renal function impairment. Clexane® has been investigated in studies in patients with renal function impairment of various severity grades, and the Summary of Product Characteristics offers clear recommendations for dosing [39].
In the steady-state, linear correlation exists between the anti-Xa plasma clearance and creatinine clearance, which indicates decreased clearance of Clexane® in patients with impaired renal function. In mild to moderate renal function impairment (creatinine clearance 50–80 ml/min or 30–50 ml/min), in the steady state after repeated subcutaneous administration of 40 mg per day the anti-Xa exposition measured as AUC is marginally increased. In those with moderate and mild renal impairment, although no dosage adjustments are recommended in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) or mild renal impairment (creatinine clearance 50-80 ml/min), careful clinical monitoring is advised.
In patients with severe renal function impairment (creatinine clearance 15-30ml/min), in the steady state after repeated subcutaneous administration of 40 mg per day, the AUC is significantly increased by an average of 65%. Therefore, in patients with severe renal failure, the dose of the dose of Clexane® needs to be adjusted, as per the table below. Enoxaparin is not recommended for patients with end stage renal disease (CrCl <15mL/min) [39].
| Indication | Dosing regimen |
|---|---|
| Prophylaxis of venous thromboembolic disease | 2,000 IU (20 mg) SC once daily |
| Treatment of DVT and PE | 100 IU/kg (1 mg/kg) body weight SC once daily |
| Treatment of unstable angina and NSTEMI | 100 IU/kg (1 mg/kg) body weight SC once daily |
| Treatment of acute STEMI (patients under 75) | 1 x 3,000 IU (30 mg) IV bolus plus 100 IU/kg (1 mg/kg) body weight SC and then 100 IU/kg (1 mg/kg) body weight SC every 24 hours |
| Treatment of acute STEMI (patients over 75) | No IV initial bolus, 100 IU/kg (1 mg/kg) body weight SC and then 100 IU/kg (1 mg/kg) body weight SC every 24 hours |
SC, subcutaneous; IV, intravenous;
The recommended dosage adjustments do not apply to the haemodialysis indication
Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 ml/min) and mild (creatinine clearance 50-80 ml/min) renal impairment, careful clinical monitoring is advised.
| Standard dosing | Severe renal inpairment |
|---|---|
| 40 mg SC once daily | 20mg SC once daily |
| 20mg SC once daily | 20mg SC once daily |
