Renal Dose Adjustment for Amoxicillin
For patients with severe renal impairment (GFR <30 mL/min), reduce amoxicillin to 500 mg or 250 mg every 12 hours, and for GFR <10 mL/min, reduce to 500 mg or 250 mg every 24 hours, with an additional dose during and after hemodialysis. 1
Dosing Algorithm Based on Renal Function
Mild to Moderate Renal Impairment (GFR ≥30 mL/min)
- No dose adjustment is generally required unless the impairment is severe 1
- Standard dosing regimens (500 mg every 12 hours or 875 mg every 12 hours) can be maintained 1
Severe Renal Impairment (GFR 10-30 mL/min)
- Reduce to 500 mg or 250 mg every 12 hours, depending on infection severity 1
- Do NOT use the 875 mg dose in patients with GFR <30 mL/min 1
- The serum half-life increases significantly from 71 minutes (normal function) to approximately 16 hours in anephric patients 2
Very Severe Renal Impairment (GFR <10 mL/min)
- Reduce to 500 mg or 250 mg every 24 hours, depending on infection severity 1
- A single 250 mg dose provides adequate serum levels for 24 hours in patients with creatinine clearance below 10 mL/min 3
Hemodialysis Patients
- Administer 500 mg or 250 mg every 24 hours (depending on severity), with timing after dialysis completion 1
- Give an additional dose both during and at the end of dialysis to compensate for drug removal 1
- The half-life during hemodialysis is approximately 2.3-3.6 hours, indicating significant dialytic clearance 2, 4
Critical Considerations and Pitfalls
Absorption Remains Intact
- Amoxicillin absorption is unimpaired in patients with renal failure, so oral dosing remains effective 3
- Adequate serum and urine levels are achieved even with severe renal impairment when appropriately dosed 3
Risk of Subtherapeutic Dosing
- Recent evidence suggests that current dose reductions may be excessive for less susceptible pathogens (MIC ≥8 mg/L), potentially leading to treatment failure 5
- For highly susceptible organisms (MIC ≤2 mg/L), reduced doses maintain adequate drug exposure (>90% probability of target attainment) 5
- Standard dosing (1000 mg every 6 hours) without reduction maintains optimal exposure even in moderate renal impairment (CKD-EPI 30 mL/min/1.73 m²) 5
Calculating Renal Function
- Use creatinine clearance corrected for body weight to determine appropriate dosing 2
- The serum half-life correlates strongly (r = 0.967) with corrected creatinine clearance 2
- Loading doses should be based on patient weight, while maintenance doses depend on creatinine clearance 2
Timing Considerations
- For hemodialysis patients, administer the dose after dialysis is complete to maximize drug retention 3
- The additional dialysis dose compensates for the 2.3-3.6 hour half-life during the procedure 1, 4
Practical Application
When prescribing amoxicillin for a patient with renal impairment, first calculate the GFR or creatinine clearance, then apply the FDA-recommended adjustments 1. For infections caused by organisms with higher MICs (approaching 8 mg/L), consider maintaining standard dosing in moderate renal impairment to avoid subtherapeutic exposure 5. Always administer supplemental doses around hemodialysis sessions to maintain therapeutic levels 1.