What is the appropriate Augmentin (amoxicillin‑clavulanate) dosing regimen for an adult patient with end‑stage renal disease on intermittent hemodialysis?

Augmentin Dosing in End-Stage Renal Disease on Hemodialysis

For ESRD patients on intermittent hemodialysis, administer Augmentin at reduced doses with extended intervals (typically 500/125 mg every 24 hours for oral or 1.2 g every 24 hours for IV), given immediately after each dialysis session on dialysis days.

Pharmacokinetic Rationale

The differential clearance of amoxicillin and clavulanic acid in ESRD creates unique dosing challenges:

• Amoxicillin accumulates significantly more than clavulanic acid in renal failure, with the ratio of amoxicillin to clavulanic acid exposure increasing from 4.9 in normal renal function to 14.7 in hemodialysis patients 1
• Both components are substantially removed by hemodialysis, with fractional drug removal of approximately 64% for amoxicillin and 65% for clavulanic acid during a 4-hour dialysis session 2
• The terminal half-life of amoxicillin extends from ~1 hour in normal patients to 13.6 hours in ESRD on non-dialysis days, but shortens to 2.3 hours during hemodialysis 2, 3

Specific Dosing Recommendations

For Intermittent Hemodialysis Patients:

• Reduce the standard dose and extend the dosing interval to prevent excessive amoxicillin accumulation while maintaining adequate clavulanic acid levels 1
• Administer immediately after each hemodialysis session on dialysis days, following the standard principle for medications in ESRD to prevent premature drug removal 4, 5, 6
• For oral dosing: 500 mg amoxicillin/125 mg clavulanic acid every 24 hours (rather than the standard every 8-12 hours) 1
• For IV dosing: 1.2 g (1000 mg amoxicillin/200 mg clavulanic acid) every 24 hours, given post-dialysis 2

Timing Considerations:

• On dialysis days: Dose immediately after the dialysis session to ensure adequate drug levels until the next treatment 4, 5, 6
• On non-dialysis days: Maintain the same extended interval (every 24 hours) to prevent amoxicillin accumulation 1

Critical Safety Considerations

Avoid Nephrotoxic Combinations:

• Do not combine with aminoglycosides (gentamicin, tobramycin, amikacin), as these are contraindicated in ESRD patients due to substantial risk of irreversible ototoxicity and should never be used as first-line therapy 5
• Aminoglycosides and tetracyclines should be avoided in CKD patients due to their nephrotoxicity 7

Monitoring Parameters:

• The nonrenal clearance of both amoxicillin and clavulanic acid is reduced in ESRD patients, suggesting some degree of hepatic impairment 2
• Total body clearance decreases more dramatically for amoxicillin (14.4 ml/min in ESRD vs. ~300 ml/min in normal patients) than for clavulanic acid (43.6 ml/min in ESRD) 2

Common Pitfalls to Avoid

• Do not use standard dosing regimens (every 8-12 hours) as this will lead to dangerous amoxicillin accumulation and potential toxicity 1
• Do not dose before dialysis on dialysis days, as approximately two-thirds of the drug will be removed during the session, leading to subtherapeutic levels 2
• Do not assume intermittent hemodialysis dosing applies to continuous renal replacement therapy (CRRT), as these are distinct modalities with different clearance characteristics 8