Amoxicillin-Clavulanate Dosing for GFR 43 mL/min
For an adult patient with a GFR of 43 mL/min/1.73 m², amoxicillin-clavulanate should be dosed at 500 mg/125 mg every 12 hours for standard infections, or 875 mg/125 mg every 12 hours for more severe infections requiring higher doses. 1
Dosing Algorithm by Infection Severity
Standard Infections
- Dose: 500 mg amoxicillin/125 mg clavulanate every 12 hours 1
- This applies to uncomplicated urinary tract infections, mild-to-moderate respiratory infections, and skin/soft tissue infections 1
Severe Infections
- Dose: 875 mg amoxicillin/125 mg clavulanate every 12 hours 1
- Consider this for pneumonia, complicated intra-abdominal infections, or when targeting resistant organisms 1
- Do not exceed 875 mg every 12 hours in this GFR range to prevent amoxicillin accumulation 2
Critical Pharmacokinetic Considerations
The dosing adjustment is necessary because amoxicillin clearance decreases more dramatically than clavulanate clearance as renal function declines 2. At a GFR of 35-75 mL/min, the ratio of amoxicillin to clavulanate exposure increases to 5.3 (compared to 4.9 at normal GFR), meaning amoxicillin accumulates disproportionately 2. This differential accumulation necessitates:
- Extended dosing intervals (every 12 hours instead of every 8 hours) 2
- Avoidance of the 1000 mg formulation in moderate renal impairment 2
- Recognition that clavulanate levels remain adequate even with reduced dosing frequency 2
Mandatory Monitoring Requirements
Initial Assessment
- Calculate eGFR using CKD-EPI or MDRD equations incorporating age, sex, and body size—do not rely on serum creatinine alone 1
- Verify the patient is not taking concomitant nephrotoxic drugs or ACE-inhibitors/ARBs that could further compromise renal function 1
Follow-up Monitoring
- Recheck serum creatinine and potassium at 5-7 days after starting therapy, particularly if the patient is on ACE-inhibitors, ARBs, or other nephrotoxic agents 1
- Assess clinical response at 48-72 hours; if no improvement, re-evaluate the dosing regimen and consider alternative pathogens or complications such as abscess formation 1
Special Population Alerts
Older Adults (≥65 years)
- The 500 mg/125 mg every 12 hours dose is appropriate, but maintain heightened vigilance for adverse effects including diarrhea and hepatotoxicity 1
- Older patients with GFR around 30-45 mL/min have increased risk of drug accumulation due to age-related changes in volume of distribution 2
Patients Approaching GFR <30 mL/min
- If GFR declines below 30 mL/min during therapy, further dose reduction is required (typically 500 mg/125 mg every 24 hours) 2
- The amoxicillin-to-clavulanate exposure ratio increases dramatically to 11.9 when GFR falls to 10-35 mL/min 2
Common Pitfalls to Avoid
- Do not use every-8-hour dosing at this GFR level, as it will cause excessive amoxicillin accumulation and increase toxicity risk 2
- Do not assume clavulanate requires the same adjustment as amoxicillin—clavulanate has significant non-renal clearance that is preserved in renal impairment 2
- Do not dose based on serum creatinine alone without calculating eGFR adjusted for age and body size, as this leads to inappropriate dosing in elderly or low-body-weight patients 1
- Avoid penicillin formulations exceeding 6 g/day when GFR <15 mL/min due to neurotoxicity risk, though this is not yet a concern at GFR 43 3