Amoxicillin Dosing for GFR 35 mL/min
For an adult with GFR 35 mL/min, standard-dose amoxicillin (500 mg every 8 hours or 1000 mg every 12 hours) requires no dose adjustment, as current evidence demonstrates that dose reductions at this level of renal function lead to subtherapeutic drug concentrations and treatment failure. 1, 2
Key Dosing Principles
No Dose Reduction Required at GFR 35 mL/min
The KDOQI guidelines explicitly state that penicillins, including amoxicillin, do not require dose adjustment until GFR falls below 15 mL/min. 1
Recent pharmacometric modeling demonstrates that recommended dose reductions in patients with impaired kidney function result in clinically relevant reductions in probability of target attainment, with only 38% achieving therapeutic levels at GFR 30 mL/min when doses are reduced. 2
For MICs ≤2 mg/L (covering most susceptible pathogens), standard dosing maintains >90% probability of target attainment even with GFR as low as 10 mL/min. 2
When Dose Adjustment IS Required (GFR <15 mL/min)
Only when GFR drops below 15 mL/min should you consider dose modifications, primarily by extending the dosing interval rather than reducing the dose. 1
For patients on hemodialysis, amoxicillin half-life extends to 2.3-3.6 hours, and a single 250-500 mg dose after dialysis provides adequate serum levels for 24 hours. 3, 4, 5
Clinical Context and Infection Severity
Standard Infections (Mild-Moderate)
For acute bacterial rhinosinusitis or uncomplicated infections, use amoxicillin 500 mg every 8 hours or high-dose amoxicillin 1000 mg every 8 hours (for resistant organisms). 1
At GFR 35 mL/min, maintain these standard doses without adjustment. 1, 2
High-Risk Situations Requiring Amoxicillin-Clavulanate
Consider amoxicillin-clavulanate (not plain amoxicillin) if the patient has used antibiotics in the past month, has moderate-to-severe infection, is >65 years old, or has diabetes/chronic disease. 1
For amoxicillin-clavulanate at GFR 35 mL/min, the ratio of amoxicillin to clavulanic acid increases (5.3:1 compared to 4.9:1 at normal GFR), but this does not require dose adjustment at this level of renal function. 6
Critical Pitfalls to Avoid
Do Not Over-Reduce Doses
The most common error is applying overly conservative dose reductions based on outdated nomograms that recommend adjustments starting at GFR 30-50 mL/min. 2, 3
These reductions were developed before modern pharmacokinetic/pharmacodynamic understanding and lead to treatment failures, particularly against less susceptible pathogens (MIC 4-8 mg/L). 2
Monitor for Specific Toxicities Only at Very Low GFR
Neurotoxicity with high-dose penicillins (>6 g/day) only occurs when GFR <15 mL/min. 1
Crystalluria risk exists only with very high doses when GFR <15 mL/min. 1
At GFR 35 mL/min, these toxicities are not clinically relevant concerns. 1
Pharmacokinetic Rationale
Amoxicillin clearance correlates strongly with creatinine clearance (r=0.967), with expected half-life of 71 minutes at normal renal function extending to approximately 2-3 hours at GFR 35 mL/min. 3, 4
This modest prolongation in half-life actually improves time above MIC without causing accumulation to toxic levels. 2
The volume of distribution and systemic availability remain independent of renal function, so loading doses never require adjustment. 6