Amoxicillin Renal Dosing
For patients with severe renal impairment (GFR <30 mL/min), reduce the amoxicillin dose by approximately 50% or double the dosing interval; for end-stage renal disease (GFR <10 mL/min), reduce to 25-50% of the normal dose and administer after hemodialysis sessions. 1
Standard Dosing Parameters
- Normal to mild renal impairment (CrCl >30 mL/min): Use standard dosing regimens without adjustment 1
- Moderate to severe impairment (CrCl 10-30 mL/min): Reduce dose by 50% OR double the dosing interval 1
- End-stage renal disease (CrCl <10 mL/min): Reduce to 25-50% of normal dose 1
The FDA label confirms that amoxicillin is primarily eliminated by the kidney and dosage adjustment is required in patients with severe renal impairment (GFR <30 mL/min). 2 High blood levels occur more readily in patients with impaired renal function due to decreased renal clearance. 2
Hemodialysis-Specific Dosing
Critical timing consideration: Always administer amoxicillin AFTER the dialysis session, never before. 1, 3
- Recommended regimen: 500 mg or 250 mg every 24 hours 1
- Supplemental dosing: Give an additional dose both during and at the end of each dialysis session to compensate for drug removal 1
- Rationale: Administering before dialysis wastes medication, leaves patients undertreated, and can lead to subtherapeutic levels and treatment failure 1
The FDA label confirms that amoxicillin may be removed from circulation by hemodialysis. 2 Research demonstrates that the half-life of amoxicillin during hemodialysis is approximately 2.3-3.6 hours, significantly shorter than in anephric patients (16 hours). 4, 5
Pharmacokinetic Basis for Adjustments
The serum half-life of amoxicillin is highly correlated with creatinine clearance (r = 0.967). 4 Expected half-life is:
Amoxicillin clearance can be well predicted using body weight and CKD-EPI calculations. 6
Important Clinical Caveats
Risk of underdosing: Recent evidence suggests that current recommended dose reductions may lead to subtherapeutic concentrations, particularly when targeting less susceptible pathogens (MIC >2 mg/L). 6 For MICs ≤2 mg/L, adequate exposure (PTA >90%) is maintained even with reduced doses. 6
Monitoring requirements:
- Patients with borderline renal function may require 24-hour urine collection to accurately define the degree of impairment before making regimen changes 1
- Close monitoring for adverse effects is warranted, as drug accumulation can occur with any degree of renal insufficiency 1
- Renal function monitoring is particularly important in elderly patients, who are more likely to have decreased renal function 2
Crystalluria risk: In case of overdosage or accumulation, maintain adequate fluid intake and diuresis to reduce the risk of amoxicillin crystalluria, which can lead to renal failure. 2 Renal impairment from crystalluria appears reversible with cessation of drug administration. 2
Special Population Considerations
Pediatric patients: Because of incompletely developed renal function in neonates and young infants, elimination of amoxicillin may be delayed, requiring dosing modifications in patients ≤12 weeks old. 2
Prophylaxis in dialysis patients: For dental or surgical prophylaxis in hemodialysis patients not allergic to penicillin, administer 2 g of amoxicillin orally 1 hour before the procedure. 7