Amoxicillin-Clavulanate Dosing for CrCl 20 mL/min
For a patient with CrCl 20 mL/min, administer amoxicillin-clavulanate 500 mg/125 mg every 12 hours for less severe infections, or 500 mg/125 mg every 12 hours for more severe infections (not the 875 mg dose). 1
FDA-Approved Dosing Recommendations
The FDA label provides clear guidance for renal impairment 1:
- CrCl 10-30 mL/min (which includes CrCl 20): 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on infection severity 1
- The 875 mg/125 mg dose is contraindicated when GFR <30 mL/min 1
- CrCl <10 mL/min: 500 mg/125 mg or 250 mg/125 mg every 24 hours 1
Practical Dosing Algorithm
For CrCl 20 mL/min, select dose based on infection severity:
- Severe infections (pneumonia, complicated UTI, severe skin/soft tissue): 500 mg/125 mg every 12 hours 1
- Less severe infections (uncomplicated UTI, mild skin infections): 250 mg/125 mg every 12 hours 1
Critical Pharmacokinetic Considerations
The differential clearance of amoxicillin versus clavulanate creates a dosing challenge in renal impairment. 2 Research demonstrates that amoxicillin clearance decreases more dramatically than clavulanate clearance as kidney function declines 2. At CrCl 10-35 mL/min, the ratio of amoxicillin to clavulanate exposure increases to 11.9 (compared to 4.9 at normal renal function), meaning amoxicillin accumulates disproportionately 2.
Standard dose reductions may lead to subtherapeutic amoxicillin concentrations, particularly for less susceptible pathogens. 3 A 2022 study showed that recommended dose adjustments resulted in only 38-62% probability of target attainment for MIC 8 mg/L at CrCl 20-30 mL/min, compared to 100% with standard dosing 3. However, for highly susceptible organisms (MIC ≤2 mg/L), reduced doses maintain >90% target attainment 3.
Common Pitfalls to Avoid
- Do not use two 250 mg/125 mg tablets to replace one 500 mg/125 mg tablet - they contain different amounts of clavulanate and are not interchangeable 1
- Do not use the 875 mg/125 mg formulation at any dosing interval when CrCl <30 mL/min 1
- Avoid underdosing for serious infections - the standard dose reductions may be insufficient for pathogens with MIC >2 mg/L, particularly in hospitalized patients 3
Hemodialysis Considerations
If the patient progresses to hemodialysis 1:
- Administer 500 mg/125 mg or 250 mg/125 mg every 24 hours (based on severity)
- Give an additional dose both during and at the end of dialysis 1
- Hemodialysis removes amoxicillin with a half-life of 2.3 hours during dialysis 4
Monitoring Recommendations
For CrCl 20 mL/min, monitor for 5, 2:
- Clinical response within 48-72 hours
- Adverse effects related to drug accumulation (particularly amoxicillin), including rash, GI disturbances, and CNS effects
- Renal function changes that may necessitate further dose adjustment 5