What is the appropriate dosing regimen of Augmentin (amoxicillin/clavulanate) for a patient with end‑stage renal disease receiving regular hemodialysis?

Augmentin Dosing in Hemodialysis Patients

For patients with end-stage renal disease on hemodialysis, administer Augmentin 500 mg/125 mg or 250 mg/125 mg every 24 hours (depending on infection severity), with an additional dose both during and at the end of each dialysis session.

Dosing Algorithm Based on Renal Function

For Hemodialysis Patients (GFR <10 mL/min on dialysis):

• Standard dose: 500 mg/125 mg every 24 hours for severe infections 1
• Reduced dose: 250 mg/125 mg every 24 hours for less severe infections 1
• Critical timing: Administer supplemental dose during dialysis AND at the end of dialysis 1

Rationale for Supplemental Dosing:

• Both amoxicillin and clavulanic acid are significantly removed by hemodialysis, with fractional drug removal of approximately 64-65% during a 4-hour dialysis session 2
• Dialysis clearance for amoxicillin is 77.1 mL/min and for clavulanic acid is 92.8 mL/min, substantially increasing total drug clearance during dialysis 2
• The half-life of amoxicillin drops from 13.6 hours between dialysis sessions to only 2.3 hours during hemodialysis 2, 3

Key Pharmacokinetic Considerations

Differential Drug Accumulation:

• Important caveat: Amoxicillin accumulates more than clavulanic acid in renal failure 4
• The ratio of amoxicillin to clavulanic acid exposure increases dramatically as renal function declines—from 4.9:1 in normal function to 14.7:1 in hemodialysis patients 4
• This differential accumulation is why the FDA-approved fixed-ratio formulations are specifically designed for renal dosing 1

Non-Renal Clearance Impairment:

• Total serum clearance on non-dialysis days is lower than in normal subjects for both components, suggesting some degree of hepatic impairment in ESRD patients 2
• This means even non-renal elimination pathways are compromised, further justifying conservative dosing 2

Formulation-Specific Restrictions

Critical warning: Do NOT use the 875 mg/125 mg tablet formulation in any patient with GFR <30 mL/min 1

Tablet Interchangeability Issues:

• Two 250 mg/125 mg tablets are NOT equivalent to one 500 mg/125 mg tablet (different clavulanic acid content) 1
• The 250 mg/125 mg tablet contains 125 mg clavulanic acid, while the 250 mg/62.5 mg chewable contains only 62.5 mg 1
• These formulations cannot be substituted for each other 1

Timing and Administration

Optimal Dosing Schedule:

• Administer the regular daily dose on non-dialysis days 1
• On dialysis days: give the regular dose, then provide supplemental doses during and after the 4-hour dialysis session 1, 2
• This timing prevents both underdosing (from dialytic removal) and excessive accumulation between sessions 2

Monitoring Requirements

Essential Clinical Monitoring:

• Assess for signs of drug accumulation, particularly with amoxicillin component (rash, GI disturbances, CNS effects) 4
• Monitor for therapeutic efficacy, as underdosing is common when supplemental dialysis doses are omitted 2
• Consider that residual renal function, if present, may provide additional drug clearance and could influence dosing needs 5

Common Pitfalls to Avoid

• Failing to give supplemental doses: The most common error is omitting the during-dialysis and post-dialysis doses, leading to subtherapeutic levels 1, 2
• Using inappropriate formulations: The 875 mg/125 mg strength is contraindicated in dialysis patients 1
• Assuming peritoneal dialysis dosing is the same: Peritoneal dialysis removes substantially less drug than hemodialysis, so these recommendations do NOT apply to CAPD patients 5
• Ignoring the differential accumulation: The disproportionate accumulation of amoxicillin versus clavulanic acid means standard ratios become skewed in ESRD 4