What is the dose adjustment of Enoxaparin (Low Molecular Weight Heparin) based on estimated Glomerular Filtration Rate (eGFR) in patients with Impaired Renal Function?

From the Guidelines

Enoxaparin dosing should be adjusted in patients with impaired renal function based on their estimated glomerular filtration rate (eGFR), with a recommended dose reduction of 50% for patients with severe renal impairment (eGFR <30 mL/min). When considering the dose adjustment of Enoxaparin based on eGFR, it is crucial to prioritize the patient's renal function to minimize the risk of bleeding complications.

• For patients with an eGFR between 30-50 mL/min, a 25% dose reduction is recommended, as supported by studies showing reduced renal clearance of enoxaparin in this population 1.
• For patients with severe renal impairment (eGFR <30 mL/min), a 50% dose reduction is typically recommended, with close monitoring of anti-Xa levels, as enoxaparin accumulation can occur, leading to increased bleeding risk 1.
• No dose adjustment is necessary for patients with an eGFR >50 mL/min, as their renal function is sufficient to clear the drug without significant accumulation.
• For prophylactic dosing in severe renal impairment, consider reducing from 40 mg daily to 30 mg daily or 20 mg daily in very severe cases, as suggested by the manufacturer's recommendations 1.
• For therapeutic dosing, reduce from 1 mg/kg twice daily to 1 mg/kg once daily when eGFR is <30 mL/min, to minimize the risk of bleeding complications while maintaining adequate anticoagulation 1. Regular monitoring of anti-Xa levels is advisable in patients with severe renal impairment to ensure appropriate anticoagulation while minimizing bleeding complications, and renal function should be reassessed periodically during treatment, especially in elderly patients or those with fluctuating renal function 1.

From the Research

Enoxaparin Dose Adjustment Based on eGFR

The dose adjustment of Enoxaparin based on estimated Glomerular Filtration Rate (eGFR) in patients with impaired renal function is a critical consideration to minimize the risk of major bleeding. The following points summarize the key findings:

• A study published in 2004 2 proposed a pharmacokinetic program to adjust enoxaparin doses based on anti-Xa levels, with a loading dose of 1 mg/kg enoxaparin, followed by 0.50 mg/kg per dose subcutaneously every 12 hours for patients with severe renal impairment (CrCl ≤30 mL/min) and 0.75 mg/kg per dose subcutaneously every 12 hours for patients with moderate renal impairment (CrCl 30-60 mL/min).
• A population pharmacokinetic analysis published in 2005 3 suggested that enoxaparin clearance is decreased by 31% in patients with moderate renal impairment and by 44% in patients with severe renal impairment, resulting in significant accumulation with the standard 1 mg/kg dosing regimen. The study proposed a dosing strategy of 0.8 mg/kg every 12 hours for patients with moderate renal impairment and 0.66 mg/kg every 12 hours for patients with severe renal impairment.
• A meta-analysis published in 2012 4 found that the use of enoxaparin is associated with an increased risk of major bleeding in patients with a GFR <60 mL/min, with a relative risk of 1.67 compared to other anticoagulants.
• However, a study published in 2009 5 found that a single bolus of enoxaparin can be administered safely without dose adjustment in patients with renal impairment undergoing percutaneous coronary intervention, with similar ischemic events and a trend for less major bleeding compared to unfractionated heparin.

Key Considerations

• The American Heart Journal study from 2004 2 and the Clinical Pharmacology and Therapeutics study from 2005 3 suggest that dose adjustment of enoxaparin based on eGFR is necessary to minimize the risk of major bleeding in patients with impaired renal function.
• The European Journal of Clinical Pharmacology meta-analysis from 2012 4 highlights the increased risk of major bleeding associated with enoxaparin use in patients with a GFR <60 mL/min.
• The American Heart Journal study from 2009 5 suggests that enoxaparin can be administered safely without dose adjustment in patients with renal impairment undergoing percutaneous coronary intervention.

Dose Adjustment Recommendations

• For patients with moderate renal impairment (CrCl 30-60 mL/min), a dose adjustment of 0.8 mg/kg every 12 hours may be considered 3.
• For patients with severe renal impairment (CrCl ≤30 mL/min), a dose adjustment of 0.66 mg/kg every 12 hours may be considered 3.
• However, the optimal dose adjustment strategy for enoxaparin in patients with impaired renal function remains unclear and may require further study 6, 4.