Enoxaparin Dosing in Renal Dysfunction
For patients with severe renal impairment (creatinine clearance <30 mL/min), enoxaparin should be dosed at 1 mg/kg subcutaneously once daily for VTE treatment and 30 mg subcutaneously once daily for VTE prophylaxis. 1
Dosing Recommendations by Renal Function
Severe Renal Impairment (CrCl <30 mL/min)
- Therapeutic dosing: 1 mg/kg subcutaneously once daily (instead of the standard twice daily regimen) 1, 2
- Prophylactic dosing: 30 mg subcutaneously once daily (instead of standard 40 mg daily) 1, 2
- Consider monitoring anti-Xa levels in patients receiving extended treatment, with target range of 0.5-1.5 IU/mL 1
Moderate Renal Impairment (CrCl 30-50 mL/min)
- Evidence suggests potential accumulation of enoxaparin with standard dosing 3, 4
- Consider dose reduction in patients with CrCl 30-50 mL/min receiving therapeutic dosing 4
- Some studies suggest using 0.8 mg/kg subcutaneously every 12 hours after an initial unadjusted dose of 1 mg/kg 4
- Standard prophylactic dosing (40 mg daily) appears appropriate for most patients 5
Rationale for Dose Adjustment
- Enoxaparin is primarily eliminated through renal excretion 1
- Renal clearance of enoxaparin is reduced by 31% in moderate renal impairment and 44% in severe renal impairment 4
- Meta-analysis shows 2-3 fold increased risk of bleeding when standard unadjusted therapeutic doses are given to patients with severe renal impairment 1
- Accumulation occurs with repeated dosing in patients with severe renal impairment, with elimination half-life increasing proportionally to the degree of renal dysfunction 5
Monitoring Considerations
- Anti-Xa monitoring should be considered for patients with severe renal impairment receiving therapeutic doses for extended periods 1
- Measure anti-Xa levels 4-6 hours after dosing, and only after the patient has received 3-4 doses 1
- Target anti-Xa range: 0.5-1.5 IU/mL for therapeutic dosing 1
Alternative Anticoagulants
- Unfractionated heparin (UFH) may be considered as an alternative in patients with severe renal impairment 1
- Comparative studies show similar rates of major bleeding between UFH and enoxaparin in patients with renal dysfunction 6
- Tinzaparin should be avoided in patients aged 70 years and older with renal insufficiency due to higher mortality rates observed in clinical trials 1
Clinical Caveats
- Patients with renal dysfunction are at higher risk of bleeding complications regardless of anticoagulant choice 6
- Female gender and prolonged duration of anticoagulation therapy are additional risk factors for bleeding in patients with renal impairment 6
- For patients with severe renal impairment receiving prophylactic enoxaparin, bioaccumulation may still occur after multiple days of therapy 5
- When switching between anticoagulants, avoid transitioning between enoxaparin and UFH due to increased bleeding risk 1