What is the appropriate dosing of Augmentin (amoxicillin-clavulanate) in patients with impaired renal function?

From the FDA Drug Label

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive the 875 mg/125 mg dose Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection Hemodialysis patients should receive 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

Dosing for Augmentin in Renal Failure:

• Mild to Moderate Renal Impairment (GFR 30 mL/min or greater): No dose reduction required.
• Severe Renal Impairment (GFR 10-30 mL/min): 500 mg/125 mg or 250 mg/125 mg every 12 hours.
• End-Stage Renal Disease (GFR less than 10 mL/min): 500 mg/125 mg or 250 mg/125 mg every 24 hours.
• Hemodialysis Patients: 500 mg/125 mg or 250 mg/125 mg every 24 hours, with an additional dose during and at the end of dialysis 1.

From the Research

For patients with renal failure, Augmentin (amoxicillin-clavulanate) dosing should be adjusted based on creatinine clearance (CrCl) and consideration of augmented renal clearance (ARC), with the goal of achieving therapeutic drug concentrations while minimizing the risk of adverse effects, as supported by the most recent study on individualized antibiotic dosage regimens 2.

Key Considerations

• Renal impairment affects the clearance of both amoxicillin and clavulanic acid, necessitating dose adjustments to prevent drug accumulation and potential toxicity.
• The presence of ARC, defined as a creatinine clearance of more than 130 mL/min/1.73 m^2, requires consideration of increased dosing to achieve therapeutic concentrations, as highlighted in studies on augmented renal clearance and antibiotic dosing 3.
• The specific formulation of Augmentin (standard, XR, ES) and its different ratios of amoxicillin to clavulanic acid should be considered in dosing decisions.
• Regular monitoring of renal function is crucial during treatment to adjust dosing as needed and minimize the risk of adverse effects.

Dosing Recommendations

• For mild renal impairment (CrCl 30-70 mL/min), standard dosing can be used, but close monitoring is recommended.
• For moderate impairment (CrCl 10-30 mL/min), consider using 250-500 mg every 12 hours, taking into account the potential for ARC and the need for therapeutic drug monitoring.
• For severe renal impairment (CrCl <10 mL/min), use 250-500 mg every 24 hours, with careful consideration of the risk of drug accumulation and potential toxicity.
• Hemodialysis patients should receive a dose after each dialysis session, with adjustments based on individual patient needs and therapeutic drug monitoring.

Therapeutic Drug Monitoring

• Given the complexities of renal clearance and the potential for ARC, therapeutic drug monitoring is essential to ensure that patients with renal failure receive optimal dosing of Augmentin, as emphasized in studies on pharmacokinetics and pharmacodynamics in critically ill patients 4, 5.
• Monitoring should include regular assessment of renal function, as well as measurement of drug concentrations to guide dose adjustments and minimize the risk of adverse effects.