How should amoxicillin dosage be adjusted for patients with impaired renal function (Estimated Glomerular Filtration Rate, EGFR) undergoing dialysis?

Amoxicillin Dosage Adjustment for Patients on Dialysis

For patients on dialysis, amoxicillin should be dosed at 500 mg or 250 mg every 24 hours (depending on infection severity), with an additional dose administered both during and at the end of dialysis. 1

Dosing Guidelines Based on Renal Function

Patients on Hemodialysis

• For patients on hemodialysis, the FDA-approved dosing regimen is 500 mg or 250 mg every 24 hours, depending on the severity of the infection 1
• An additional dose should be administered both during and at the end of dialysis sessions to compensate for drug removal during the dialysis procedure 1
• The half-life of amoxicillin during hemodialysis is approximately 2.3 hours, necessitating supplemental dosing 2

Patients with Severe Renal Impairment

• For patients with GFR less than 10 mL/min (not on dialysis), the recommended dosage is 500 mg or 250 mg every 24 hours, depending on the severity of infection 1
• For patients with GFR between 10-30 mL/min, the recommended dosage is 500 mg or 250 mg every 12 hours, depending on infection severity 1
• The 875 mg dose of amoxicillin should NOT be used in patients with GFR less than 30 mL/min 1

Pharmacokinetic Considerations

• Amoxicillin follows a two-compartment model with significant changes in patients with renal failure 2
• In renal failure patients, there is a significant decrease in elimination rate (β), renal clearance (κ10), and total body clearance 2
• A linear relationship exists between the elimination rate of amoxicillin and creatinine clearance, which forms the basis for dosage adjustments 2

Clinical Considerations and Cautions

• Standard dose reductions in patients with impaired kidney function could potentially lead to subtherapeutic amoxicillin concentrations, especially when targeting less susceptible pathogens with MICs > 2 mg/L 3
• For infections caused by organisms with MICs ≤ 2 mg/L, both reduced and standard dose regimens can achieve adequate target attainment in patients with impaired renal function 3
• Close monitoring of drug effect and toxicity is essential in patients with renal dysfunction 4
• Therapeutic drug monitoring may be beneficial in patients with severe renal impairment to ensure adequate drug exposure while minimizing toxicity 4

Important Caveats

• The absorption half-life of amoxicillin is significantly increased in patients with renal impairment, which may affect the timing of peak concentrations 2
• Inappropriate dosing in patients with renal dysfunction can cause toxicity or ineffective therapy, highlighting the importance of appropriate dose adjustment 5
• Renal dysfunction affects more than just the renal handling of drugs; it can also impact drug metabolism and protein binding 5