From the FDA Drug Label
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive the 875 mg/125 mg dose Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection Hemodialysis patients should receive 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
The recommended renal dose of amoxicillin-clavulanate is as follows:
- For patients with a glomerular filtration rate of 10 to 30 mL/min: 500 mg/125 mg or 250 mg/125 mg every 12 hours.
- For patients with a glomerular filtration rate less than 10 mL/min: 500 mg/125 mg or 250 mg/125 mg every 24 hours.
- For hemodialysis patients: 500 mg/125 mg or 250 mg/125 mg every 24 hours, with an additional dose both during and at the end of dialysis 1.
From the Research
Amoxicillin-clavulanate requires dose adjustment in patients with renal impairment, with the most recent and highest quality study suggesting that for adults with creatinine clearance (CrCl) 30-60 mL/min, use 500/125 mg every 12 hours, and for CrCl 10-30 mL/min, reduce to 500/125 mg every 24 hours 2.
Key Considerations
- In severe renal impairment (CrCl <10 mL/min), the dose should be 500/125 mg every 24 hours, with additional consideration for hemodialysis patients who should receive doses after dialysis sessions.
- For children with renal impairment, reduce the frequency rather than the dose strength, following similar principles based on creatinine clearance.
- These adjustments are necessary because both amoxicillin and clavulanic acid are primarily eliminated by the kidneys, and accumulation in renal failure can lead to toxicity, with clavulanic acid accumulation being particularly concerning as it can cause central nervous system effects 3.
Dosing Recommendations
- Always calculate the patient's creatinine clearance using the Cockcroft-Gault formula or other appropriate methods before prescribing, and monitor renal function during treatment, especially in elderly patients or those with fluctuating kidney function.
- Consider augmented renal clearance (ARC) in critically ill patients, which may require increased dosing of amoxicillin-clavulanic acid to achieve therapeutic targets 4.
- For patients with ARC, a 1-h infusion may be preferable to bolus dosing, and four-hourly dosing of 25 mg/kg may be required to achieve the therapeutic target for both amoxicillin and clavulanic acid 2.