Amoxicillin-Clavulanate Dosing Regimens

Pharmacokinetic Rationale

• The American Academy of Otolaryngology-Head and Neck Surgery notes that clavulanate causes gastrointestinal toxicity in a dose-dependent manner, with diarrhea becoming problematic when the daily clavulanate dose exceeds approximately 10 mg/kg per day 1
• The American Academy of Otolaryngology-Head and Neck Surgery also states that three-times-daily dosing of amoxicillin-clavulanate historically caused high rates of gastrointestinal side effects compared to alternative antibiotics, making compliance difficult 1

Pharmacodynamics of Amoxicillin

• Amoxicillin has a shorter half-life of approximately 1 hour and requires more frequent dosing to maintain adequate serum concentrations above the minimum inhibitory concentration for time-dependent bacterial killing 2
• The Infectious Diseases Society of America implies that pharmacodynamic optimization for beta-lactams like amoxicillin requires maintaining drug concentrations above the minimum inhibitory concentration for 40-50% of the dosing interval, which is more reliably achieved with three-times-daily dosing for standard amoxicillin formulations 2