Amoxicillin-Clavulanate Renal Dosing
For patients with severe renal impairment (GFR <30 mL/min), avoid the 875 mg dose entirely and reduce standard dosing 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, 2
Dosing Algorithm by Renal Function
Normal to Mild Impairment (GFR >30 mL/min)
- No dose adjustment required - use standard dosing regimens 2, 1
- Standard severe infection dose: 875 mg every 12 hours 1
- Patients with impaired renal function do not generally require dose reduction unless the impairment is severe 1
Moderate Impairment (GFR 10-30 mL/min)
- Reduce dose by 50% OR double the dosing interval 2
- The 875 mg tablet formulation should NOT be used in this population 1
- Alternative approach: use lower strength formulations with extended intervals 2
Severe Impairment/End-Stage Renal Disease (GFR <10 mL/min)
- Reduce to 25-50% of normal dose 2
- Administer dose after hemodialysis sessions, not before 2, 3
- Post-dialysis timing ensures adequate drug exposure and prevents premature removal 2
- Hemodialysis removes approximately 35-45% of amoxicillin during a 4-hour session 3
Critical Monitoring Considerations
Before Initiating Therapy
- Assess renal function before starting treatment and periodically during therapy 4
- For patients with fluctuating renal function, reassess GFR every 2-3 days to adjust dosing 4
- Elderly patients require special attention - they often have decreased renal function even with normal serum creatinine levels 4, 1
Borderline Cases
- Patients with borderline renal function may require 24-hour urine collection to accurately define the degree of impairment before making regimen changes 2
- Close monitoring for adverse effects is warranted, as drug accumulation can occur with any degree of renal insufficiency 2
Common Pitfalls to Avoid
Dosing Errors
- Do NOT assume all antibiotics require the same degree of adjustment - individualized adjustments are necessary 2
- Avoid administering before dialysis - this wastes medication and leaves patients undertreated 2
- Current dose reductions may lead to subtherapeutic concentrations, especially when targeting less susceptible pathogens (MIC ≥4-8 mg/L) 5
Special Populations
- Neonates and young infants: Amoxicillin elimination may be delayed due to incompletely developed renal function 1
- Nursing mothers: Amoxicillin is excreted in human milk and may lead to infant sensitization 1
- Geriatric patients: Greater sensitivity cannot be ruled out; monitor renal function closely as this drug is substantially excreted by the kidney 1
Pharmacokinetic Basis
- Amoxicillin half-life correlates highly with creatinine clearance (r = 0.967) 6
- Expected half-life: 71 minutes with normal function versus 16 hours in anephric patients 6
- Average half-life during hemodialysis: 2.3-3.6 hours 6, 7
- Average urinary recovery in normal function: 68% 6
Alternative Considerations
- For respiratory infections in patients with renal impairment, consider respiratory fluoroquinolones with appropriate renal dose adjustments as alternative agents 4
- Consult infectious disease specialists and clinical pharmacists for optimal antimicrobial selection in patients with severe infections and significant renal impairment 4