Amoxicillin with Clavulanate Dosing Recommendations
For adults with respiratory infections, the standard dose is 500 mg/125 mg every 12 hours or 875 mg/125 mg every 12 hours, with the higher dose recommended for more severe infections. 1
Adult Dosing
- For mild to moderate infections, the standard dose is 500 mg amoxicillin/125 mg clavulanate every 12 hours or 250 mg/125 mg every 8 hours 1
- For more severe infections and respiratory tract infections, the recommended dose is 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours 1
- High-dose amoxicillin-clavulanate (2 g orally twice daily) is recommended for areas with high prevalence of resistant pathogens or in patients with risk factors for resistant infections 2, 3
- Risk factors warranting high-dose therapy include: recent antibiotic use, close contact with treated individuals, failed previous antibiotic therapy, high prevalence of resistant bacteria, moderate to severe infections, frontal or sphenoidal sinusitis, history of recurrent infections, comorbidities, immunocompromised status, or age over 65 3, 4
Pediatric Dosing
- For neonates and infants <12 weeks: 30 mg/kg/day divided every 12 hours (based on amoxicillin component) 1
- For children ≥12 weeks with less severe infections: 25 mg/kg/day every 12 hours or 20 mg/kg/day every 8 hours 4, 1
- For children ≥12 weeks with more severe infections (otitis media, sinusitis, lower respiratory tract infections): 45 mg/kg/day every 12 hours or 40 mg/kg/day every 8 hours 1
- High-dose amoxicillin-clavulanate for children is defined as 90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in two divided doses 5, 4
- Children weighing ≥40 kg should be dosed according to adult recommendations 1
- The twice-daily regimen is associated with significantly less diarrhea than three-times-daily dosing 1, 6
Special Considerations
- Amoxicillin-clavulanate should be taken at the start of a meal to enhance absorption of clavulanate and minimize gastrointestinal intolerance 1
- For acute bacterial sinusitis, amoxicillin-clavulanate is recommended over amoxicillin alone in both adults (weak recommendation, low quality evidence) and children (strong recommendation, moderate quality evidence) 2
- Treatment duration for uncomplicated acute bacterial sinusitis in adults is 5-7 days 2, 3
- For children with acute bacterial sinusitis, a longer treatment duration of 10-14 days is recommended 2, 5
- Patients with renal impairment (GFR <30 mL/min) should not receive the 875 mg/125 mg dose 1
Clinical Pearls and Pitfalls
- Two 250 mg/125 mg tablets should not be substituted for one 500 mg/125 mg tablet, as they are not equivalent in amoxicillin content despite containing the same amount of clavulanic acid 1
- The 250 mg/125 mg tablet and the 250 mg/62.5 mg chewable tablet are not interchangeable due to different amounts of clavulanic acid 1
- High-dose immediate-release amoxicillin-clavulanate has shown better clinical improvement at day 3 compared to standard-dose therapy in adults with acute bacterial sinusitis, but with increased risk of severe diarrhea 7
- Recent research suggests that high-dose amoxicillin-clavulanate may not provide additional benefit over standard-dose in adults with acute sinusitis, highlighting the importance of appropriate dose selection based on individual patient factors and local resistance patterns 8
- Once or twice daily dosing of amoxicillin-clavulanate has shown comparable efficacy to three-times-daily dosing, which may improve medication adherence 6