What is the appropriate dosing of amoxicillin‑clavulanate (Augmentin) in an adult with an estimated glomerular filtration rate of approximately 45 mL/min/1.73 m²?

Augmentin Dosing with GFR 45 mL/min/1.73 m²

For a patient with a GFR of 45 mL/min/1.73 m², standard-dose Augmentin (amoxicillin-clavulanate) should be dose-reduced to prevent amoxicillin accumulation while maintaining adequate clavulanic acid levels.

GFR Classification and Risk Category

• A GFR of 45 mL/min/1.73 m² falls into the G3a category (moderately reduced GFR: 45-59 mL/min/1.73 m²), representing moderate chronic kidney disease. 1
• This level of renal function requires careful medication dosing adjustments for renally-cleared antibiotics. 1

Pharmacokinetic Rationale for Dose Adjustment

• Amoxicillin clearance decreases more dramatically than clavulanic acid clearance as renal function declines, leading to disproportionate accumulation of amoxicillin relative to clavulanic acid. 2
• At a GFR of 35-75 mL/min/1.73 m² (which includes your patient's GFR of 45), the ratio of amoxicillin to clavulanic acid area-under-curve increases to 5.3 ± 2.4 compared to 4.9 ± 1.2 at normal GFR. 2
• This differential accumulation necessitates dose reduction to prevent amoxicillin toxicity (particularly neurotoxicity with high doses) while maintaining therapeutic clavulanic acid levels. 2

Specific Dosing Recommendations

For Mild to Moderate Infections

• Reduce the standard dose by 50% or extend the dosing interval from every 8 hours to every 12 hours. 1
• A practical regimen would be Augmentin 500/125 mg every 12 hours instead of every 8 hours for mild-moderate infections. 2
• Alternatively, use Augmentin 250/125 mg every 8 hours for less severe infections. 2

For Severe Infections Requiring Higher Doses

• If higher doses are clinically necessary, do not exceed 6 grams per day of amoxicillin component to avoid neurotoxicity risk. 1
• Monitor closely for signs of drug accumulation, including neurological symptoms. 1

Clinical Evidence Supporting Dose Adjustment

• A study of 88 patients with urogenital infections, including 26 patients with GFR 55-70 mL/min/1.73 m² (similar to your patient), demonstrated that Augmentin 375 mg three times daily for 6-12 days was effective and well-tolerated in patients with mild renal impairment. 3
• This supports the safety and efficacy of reduced-dose regimens in this GFR range. 3

Critical Monitoring Parameters

• Assess renal function before initiating therapy to confirm the GFR and guide initial dosing. 1
• Monitor for signs of drug accumulation, particularly if treatment extends beyond 7-10 days, including neurological symptoms (confusion, seizures with very high doses). 1
• Avoid concomitant nephrotoxic agents (NSAIDs, aminoglycosides) that could further compromise renal function. 1

Common Pitfalls to Avoid

• Do not use standard full-dose regimens (e.g., 875/125 mg every 8 hours) without dose adjustment at this GFR level, as amoxicillin will accumulate excessively. 2
• Do not assume the fixed-ratio formulation maintains optimal proportions in renal impairment—the pharmacokinetics change differentially for the two components. 2
• Do not overlook the risk of crystalluria if very high doses are used when GFR approaches 15 mL/min/1.73 m², though this is less of a concern at GFR 45. 1
• Temporarily suspend or further reduce the dose if the patient develops acute illness, dehydration, or receives IV contrast that could acutely worsen renal function. 1