What is the recommended dosing of Lovenox (enoxaparin) in patients with impaired renal function?

From the Guidelines

Enoxaparin (Lovenox) dosing should be reduced in patients with impaired renal function, with a recommended dose of 1 mg/kg subcutaneously every 24 hours for patients with creatinine clearance (CrCl) less than 30 mL/min, as stated in the 2013 ACCF/AHA guideline 1.

Key Considerations

• For patients with CrCl less than 30 mL/min, the dose is reduced to 1 mg/kg subcutaneously every 24 hours, which is a significant reduction from the standard dose.
• The dose reduction is necessary because enoxaparin is primarily eliminated by the kidneys, and decreased renal function leads to drug accumulation, increasing the risk of bleeding complications.
• Regular monitoring of anti-Factor Xa levels may be beneficial in patients with renal impairment to ensure appropriate anticoagulation while minimizing bleeding risk.
• Renal function should be assessed before initiating therapy and periodically during treatment, especially in elderly patients, those with known renal insufficiency, or those at risk for acute kidney injury.

Additional Guidance

• Patients with moderate renal impairment (CrCl 30-50 mL/min) should be monitored closely, though formal dose adjustment is not always required, as suggested by the study in the Journal of the National Comprehensive Cancer Network 1.
• The study also recommends monitoring of peak anti-Xa levels to achieve a target range of 0.5 to 1.5 IU/mL for patients with cancer and CrCl less than 30 mL/min receiving dalteparin for extended treatment of acute VTE.
• However, the primary focus for enoxaparin dosing in renal failure remains on the adjusted dose for severe renal impairment, as outlined in the ACCF/AHA guideline 1.

From the Research

Lovenox Dosing in Renal Failure

• The recommended dosing of Lovenox (enoxaparin) in patients with impaired renal function is a topic of interest due to the increased risk of bleeding complications in this population 2, 3.
• Studies have shown that enoxaparin clearance is reduced in patients with renal impairment, resulting in a significant accumulation of the drug with standard dosing regimens 4, 5.
• A retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment found that a loading dose of 1 mg/kg followed by a regimen of 0.50 mg/kg per dose subcutaneously every 12 hours for patients with creatinine clearance ≤30 mL/min and 0.75 mg/kg per dose subcutaneously every 12 hours for patients with creatinine clearance of 30 to 60 mL/min was effective in achieving therapeutic anti-Xa levels 4.
• A population pharmacokinetic analysis suggested that a dosing strategy of 1 mg/kg followed by a regimen of 0.8 mg/kg every 12 hours in patients with moderate renal impairment or 0.66 mg/kg every 12 hours in patients with severe renal impairment should avoid accumulation of enoxaparin and keep peak anti-Xa activities between 0.5 and 1.2 IU/mL for a large majority of patients 5.
• A review of enoxaparin treatment dosing, pharmacokinetics, and clinical outcomes data in patients with renal impairment suggested that a more multitiered enoxaparin renal dosing strategy, shifting from the current two-tier approach to at least three or four tiers, should be considered 6.

Key Findings

• Enoxaparin clearance is reduced in patients with renal impairment, resulting in a significant accumulation of the drug with standard dosing regimens 4, 5.
• A dose-adjustment ratio can be used to adjust enoxaparin doses in patients with renal impairment to achieve therapeutic anti-Xa levels 4.
• Individualized enoxaparin dosing may result in a decreased risk of bleeding compared to the current FDA-approved two-tiered scheme 6.
• Reduced-dose enoxaparin may be associated with a trend toward lower incidences of thromboembolism and 30-day mortality, as well as decreased hospital length of stay, compared to unfractionated heparin 6.