Amoxicillin-Clavulanate Dosing Recommendations
The recommended dosing for amoxicillin-clavulanate varies based on patient age, infection severity, and risk factors for resistant pathogens, with standard adult dosing being 500/125 mg every 8 hours or 875/125 mg every 12 hours for most infections, while high-dose formulations (2000/125 mg twice daily for adults or 90/6.4 mg/kg/day in two divided doses for children) are recommended for suspected resistant pathogens. 1, 2
Adult Dosing
Standard Dosing
- For adults with mild to moderate infections without risk factors for resistant pathogens: 500/125 mg every 8 hours or 875/125 mg every 12 hours for 7-10 days 3, 1
- The 875/125 mg every 12 hours regimen has been shown to be as effective as the 500/125 mg every 8 hours regimen, with comparable clinical success rates (93% vs. 94%) 4
- The twice-daily regimen may be associated with less moderate or severe diarrhea compared to the three-times-daily regimen 4
High-Dose Regimen
- For adults with risk factors for resistant pathogens: 2000/125 mg (high-dose amoxicillin component) twice daily 1, 2
- Risk factors warranting high-dose therapy include: 1, 2
- Recent antibiotic use (within 4-6 weeks)
- Treatment failure with standard dosing
- Moderate to severe infections (e.g., frontal or sphenoidal sinusitis)
- Comorbid conditions or immunocompromised status
- Age >65 years
- High prevalence of resistant bacteria in the community
Pediatric Dosing
Standard Dosing
- For children with mild infections: 25 mg/kg/day of amoxicillin component divided every 12 hours or 20 mg/kg/day divided every 8 hours 1
- For moderate infections: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours 1, 2
High-Dose Regimen
- For children with risk factors for resistant pathogens: 90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate divided into two doses 1, 2, 5
- Pediatric risk factors include: 1, 2
- Age under 2 years
- Daycare attendance
- Recent antibiotic use (within 30 days)
- Concurrent conjunctivitis (suggesting Moraxella catarrhalis)
- Areas with high prevalence of penicillin-resistant Streptococcus pneumoniae (>10%)
Duration of Therapy
- Respiratory infections: 7-10 days 1
- Sinusitis: 10-14 days or until the patient is symptomatically improved for 7 days 1
- Uncomplicated urinary tract infections: 3-7 days 1
Special Considerations
Pharmacokinetics
- The high-dose formulation for adults (2000/125 mg) consists of immediate-release and sustained-release components designed to maintain plasma amoxicillin concentrations above the MIC for a longer period 6
- The terminal half-lives of amoxicillin (1.27 hours) and clavulanate (1.03 hours) are similar across different formulations 6
Efficacy Against Resistant Pathogens
- High-dose amoxicillin-clavulanate provides better coverage against penicillin-resistant Streptococcus pneumoniae 5
- The 14:1 ratio of amoxicillin to clavulanate in the high-dose pediatric formulation is less likely to cause diarrhea than other preparations 2
Adverse Effects
- The most common adverse effects are gastrointestinal disturbances, particularly diarrhea 7
- Diarrhea is generally less frequent with twice-daily dosing compared to three-times-daily dosing 5
- Clavulanic acid dose is restricted to 125 mg in adult formulations due to tolerability issues 8
Common Pitfalls and Caveats
- A recent randomized clinical trial found no significant benefit of high-dose versus standard-dose amoxicillin-clavulanate for adults with acute sinusitis, with 44.3% of standard-dose and 36.4% of high-dose patients reporting improvement at day 3 9
- Probenecid decreases the renal tubular secretion of amoxicillin and may increase blood concentrations; co-administration is not recommended 7
- Amoxicillin-clavulanate may affect intestinal flora, potentially reducing the efficacy of oral contraceptives 7
- Concurrent use with allopurinol may increase the incidence of rashes 7
- Monitoring is recommended when anticoagulants are prescribed concurrently with amoxicillin-clavulanate, as abnormal prolongation of prothrombin time has been reported 7