Renal Dosing for Amoxicillin-Clavulanate
Yes, amoxicillin-clavulanate requires renal dose adjustments in patients with impaired kidney function, with specific modifications based on glomerular filtration rate (GFR). 1
Dosing Adjustments by Renal Function
The FDA-approved dosing modifications are stratified by severity of renal impairment:
Severe Renal Impairment (GFR <30 mL/min)
- The 875 mg/125 mg dose is contraindicated in patients with GFR <30 mL/min 1
- Use 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on infection severity 1
Moderate Renal Impairment (GFR 10-30 mL/min)
- Administer 500 mg/125 mg or 250 mg/125 mg every 12 hours based on infection severity 1
- This represents a reduction in dosing frequency from the standard every 8-12 hour regimen 1
Severe Renal Impairment (GFR <10 mL/min)
- Further reduce frequency to 500 mg/125 mg or 250 mg/125 mg every 24 hours 1
- Severity of infection determines which dose strength to use 1
Hemodialysis Patients
- Administer 500 mg/125 mg or 250 mg/125 mg every 24 hours 1
- Give an additional dose both during and at the end of dialysis to compensate for drug removal 1
- This recommendation follows the established principle of post-dialysis dosing to prevent premature drug removal 2
Pharmacokinetic Rationale
The need for dose adjustment is driven by differential effects on the two components:
- Amoxicillin clearance is highly dependent on renal function, with serum half-life increasing from 71 minutes (normal function) to 16 hours (anephric patients) 3
- Clavulanic acid is less affected by renal impairment than amoxicillin, leading to a changing ratio between the two components as kidney function declines 4
- The ratio of amoxicillin to clavulanic acid increases dramatically with worsening renal function: from 4.9 (GFR 75 mL/min) to 14.7 (hemodialysis patients) 4
- Hemodialysis removes both components, with clavulanic acid having a higher extraction ratio (0.74) compared to amoxicillin (0.44) 2
Critical Pitfalls to Avoid
Do not substitute tablet strengths inappropriately in renal failure. Two 250 mg/125 mg tablets are NOT equivalent to one 500 mg/125 mg tablet because they contain different total amounts of clavulanic acid (250 mg vs. 125 mg), which becomes particularly important when renal clearance is impaired 1
Monitor for drug accumulation in chronic renal failure, as both components accumulate but at different rates, potentially leading to suboptimal ratios for beta-lactamase inhibition 2