Amoxicillin-Clavulanate Dosing in Renal Failure
Amoxicillin-clavulanate requires dose adjustment in patients with severe renal impairment (GFR <30 mL/min), with the standard recommendation being to avoid the 875 mg tablet formulation and instead use lower doses with extended intervals to prevent amoxicillin accumulation while maintaining adequate clavulanate levels. 1
Key Dosing Principles
The critical issue with amoxicillin-clavulanate in renal failure is that amoxicillin accumulates more significantly than clavulanate as kidney function declines, creating a widening ratio between the two components that can lead to amoxicillin toxicity if standard doses are maintained. 2
Renal Function-Based Adjustments
For GFR <30 mL/min (severe renal impairment): Dosage adjustment is required because amoxicillin is primarily eliminated by the kidney, and the risk of adverse reactions increases substantially in patients with impaired renal function. 1
The pharmacokinetic data demonstrates that as GFR decreases, total body clearance of amoxicillin drops more dramatically than clavulanate clearance, resulting in disproportionate accumulation. 2
Specific dosing recommendations for severe renal impairment (GFR <30 mL/min):
Hemodialysis Considerations
For patients on hemodialysis: Amoxicillin is cleared during dialysis with a half-life of approximately 2.3-3.6 hours during the procedure. 4, 3
Administer the dose after hemodialysis to avoid premature drug removal and ensure adequate therapeutic levels. 4
A supplementary dose may be needed post-dialysis since hemodialysis effectively removes amoxicillin due to its low molecular weight and reduced protein binding. 5
Elderly Patients
Greater caution is warranted in elderly patients because they are more likely to have decreased renal function, even if not formally diagnosed with renal impairment. 1
Monitor renal function and select doses carefully in this population to prevent accumulation-related toxicity. 1
Clinical Monitoring
Assess baseline renal function using creatinine clearance or GFR before initiating therapy. 3, 2
The correlation between amoxicillin half-life and creatinine clearance is highly significant (r = 0.967), allowing for precise dosage adjustments based on measured renal function. 3
Monitor for dose-related toxicity, particularly neurological symptoms, as amoxicillin can accumulate to toxic levels in severe renal impairment. 6
Important Caveats
The fixed-ratio combination becomes problematic in renal failure because the area under the curve (AUC) ratio of amoxicillin to clavulanate increases dramatically—from approximately 4.9:1 in normal renal function to 14.7:1 in hemodialysis patients. 2
Absorption is also affected: Patients with renal impairment show a significant increase in the absorption half-life of amoxicillin, which further complicates dosing. 4
Do not use standard dosing tables without adjustment—a 30% dose reduction is recommended for each level of renal impairment (moderate and severe). 5