Dosing of Amoxicillin-Clavulanate in Renal Impairment
Patients with renal impairment require specific dose adjustments of amoxicillin-clavulanate based on their glomerular filtration rate (GFR). The following recommendations are based on the FDA drug label and clinical guidelines.
Dosing Recommendations Based on Renal Function
- GFR ≥30 mL/min: Standard dosing of amoxicillin-clavulanate can be used 1
- GFR 10-30 mL/min: Use 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on infection severity 1
- GFR <10 mL/min: Use 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on infection severity 1
- Hemodialysis patients: Use 500 mg/125 mg or 250 mg/125 mg every 24 hours with an additional dose both during and at the end of dialysis 1
- Important restriction: Patients with GFR <30 mL/min should NOT receive the 875 mg/125 mg dose formulation 1
Pharmacokinetic Considerations
- In renal impairment, amoxicillin clearance decreases more significantly than clavulanic acid clearance, leading to disproportionate accumulation of amoxicillin 2
- The ratio of amoxicillin to clavulanic acid increases as renal function declines (from approximately 5:1 with normal renal function to 15:1 in patients on hemodialysis) 2
- The half-life of amoxicillin is highly correlated with creatinine clearance, increasing from approximately 1.2 hours with normal renal function to 16 hours in anephric patients 3
- During hemodialysis, the half-life of amoxicillin is reduced to approximately 2.3-3.6 hours 3, 4
Monitoring Recommendations
- Assess renal function before initiating therapy and periodically during treatment 5
- For patients with fluctuating renal function, reassess GFR every 2-3 days to adjust dosing as needed 5
- Monitor for signs of toxicity, particularly in patients with severe renal impairment, as drug accumulation may occur 2
- Pay special attention to elderly patients who often have decreased renal function even with normal serum creatinine levels 5
Clinical Pearls and Pitfalls
- Hemodialysis increases the clearance of both amoxicillin and clavulanic acid, with clavulanic acid being affected to a greater extent (extraction ratio 0.74 vs. 0.44 for amoxicillin) 6
- In critically ill patients receiving renal replacement therapy, higher doses and more frequent administration may be needed to maintain adequate antimicrobial coverage 7
- The systemic availability of both amoxicillin and clavulanic acid remains independent of renal function, but total body clearance decreases with declining renal function 2
- Dosage adjustments are essential to prevent undue accumulation of amoxicillin while maintaining adequate concentrations of clavulanic acid 2
Alternative Antimicrobials in Severe Renal Impairment
- For patients with severe infections and significant renal impairment, consider consulting with infectious disease specialists and clinical pharmacists for optimal antimicrobial selection 5
- When treating respiratory infections in patients with renal impairment, respiratory fluoroquinolones (with appropriate renal dose adjustments) may be considered as alternative agents 5