What are the dose adjustments for Augmentin (amoxicillin/clavulanate) in patients with impaired renal function?

Augmentin Dose Adjustments in Renal Impairment

For patients with creatinine clearance >30 mL/min, use standard Augmentin dosing without adjustment, but reduce doses by approximately 50% or double the dosing interval for creatinine clearance 10-30 mL/min, and further reduce to 25-50% of normal dose for end-stage renal disease (CrCl <10 mL/min). 1

Dosing Based on Renal Function

Normal to Mild Renal Impairment (CrCl >30 mL/min)

• No dose adjustment is required for patients with creatinine clearance above 30 mL/min 1
• Standard adult dosing remains appropriate: 500 mg/125 mg every 12 hours or 250 mg/125 mg every 8 hours for routine infections 2
• For severe infections or respiratory tract involvement: 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours 2

Moderate to Severe Renal Impairment (CrCl 10-30 mL/min)

• Reduce the dose by approximately 50% OR double the dosing interval 1
• This represents a critical threshold where both amoxicillin and clavulanate accumulation becomes clinically significant 2
• Monitor for gastrointestinal side effects, which may increase with accumulation 2

End-Stage Renal Disease (CrCl <10 mL/min)

• Further dose reduction to 25-50% of the normal dose is required 1
• Both amoxicillin and clavulanate are removed by hemodialysis 2, 3
• Approximately 64% of amoxicillin and 65% of clavulanic acid are removed during a 4-hour hemodialysis session 3

Hemodialysis Considerations

Timing of Administration

• Always administer Augmentin after the dialysis session, not before 1, 4
• Post-dialysis dosing prevents premature drug removal and ensures adequate drug exposure 1
• This timing facilitates directly observed therapy and avoids wasting medication 1

Pharmacokinetic Changes in Dialysis Patients

• The half-life of amoxicillin extends from approximately 1 hour in normal patients to 13.6 hours in end-stage renal disease on non-dialysis days 3
• During dialysis, the half-life shortens to 2.3 hours for amoxicillin and 1.19 hours for clavulanic acid 3
• Total serum clearance on non-dialysis days is significantly reduced, suggesting some degree of hepatic impairment may coexist in ESRD patients 3

Important Clinical Pitfalls

Crystalluria Risk

• Maintain adequate fluid intake and diuresis in patients with renal impairment to reduce the risk of amoxicillin crystalluria 2
• Crystalluria can lead to acute renal failure, particularly after overdosage or in patients with pre-existing renal dysfunction 2
• Interstitial nephritis with oliguric renal failure has been reported in patients with amoxicillin accumulation 2

Monitoring Requirements

• High blood levels occur more readily in patients with impaired renal function due to decreased clearance of both components 2
• Renal impairment from drug-related nephrotoxicity appears reversible with drug cessation 2
• In patients with chronic kidney disease and latent renal insufficiency (GFR 55-70 mL/min), Augmentin has been used successfully with standard dosing for 6-12 days 5

Hepatic Function Considerations

• Hepatically impaired patients require cautious dosing with regular hepatic function monitoring 2
• This is particularly important in ESRD patients who may have concurrent hepatic impairment 3

Practical Dosing Algorithm

1. Calculate creatinine clearance using the Cockcroft-Gault equation or estimate GFR 6, 7
2. If CrCl >30 mL/min: Use standard dosing without adjustment 1
3. If CrCl 10-30 mL/min: Reduce dose by 50% OR extend interval to every 24 hours instead of every 12 hours 1
4. If CrCl <10 mL/min or on hemodialysis: Use 25-50% of normal dose and administer after dialysis 1, 2
5. Ensure adequate hydration in all patients with renal impairment 2