Upper Dose Limits of Oral Amoxicillin
The maximum daily dose of oral amoxicillin is 4 grams per day for adults and 90 mg/kg per day for children, with specific formulations allowing higher doses when combined with clavulanic acid. 1, 2
Adult Dosing Limits
- Standard adult dosing range is 750 to 1750 mg/day divided every 8 to 12 hours according to FDA labeling 2
- For respiratory infections requiring higher coverage against resistant organisms, high-dose amoxicillin is defined as 4 g/day 1
- When treating H. pylori infections, the maximum dose is 1 gram three times daily (3 g/day) when used in dual therapy with lansoprazole 2
- For patients with severe renal impairment (GFR >30 mL/min), dose reduction is required 2
Pediatric Dosing Limits
- Standard pediatric dosing is 20 to 45 mg/kg/day divided every 8 to 12 hours 2
- For neonates and infants ≤3 months, the upper limit is 30 mg/kg/day divided every 12 hours 2
- For Group A streptococcal pharyngitis, the maximum dose is 50 mg/kg once daily (maximum 1,000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) 1
- For respiratory tract infections with resistant pathogens, high-dose amoxicillin for children is defined as 90 mg/kg/day 1
- For uncomplicated urinary tract infections in children, amoxicillin can be dosed at 40-90 mg/kg/day in 2-3 divided doses (maximum 4000 mg/day) 1
Special Situations with Higher Dosing
- For community-acquired pneumonia in children, doses of 70-90 mg/kg/day have been studied and shown to be as safe as lower doses (35-50 mg/kg/day) 3
- For single-dose prophylaxis for bacterial endocarditis in adults, 2.0 g has been shown to be effective and better tolerated than 3.0 g 4
- For acute otitis media with resistant organisms, especially during viral coinfection, doses of 75-90 mg/kg/day may be recommended 5
Amoxicillin-Clavulanate Combinations
- High-dose amoxicillin/clavulanate is defined as 4 g of amoxicillin with 250 mg of clavulanate per day for adults 1
- For children, high-dose amoxicillin/clavulanate is 90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate (in two divided doses) 1
- For chronic carriers of Group A Streptococcus, amoxicillin/clavulanate can be dosed at 40 mg amoxicillin per kg per day in three doses (maximum 2,000 mg amoxicillin per day) 1
Clinical Considerations
- The upper limit of amoxicillin is often determined by gastrointestinal tolerability rather than toxicity concerns 1
- Serum levels of amoxicillin increase linearly with dose, as gastrointestinal absorption is not a limiting factor 1
- The difference in adverse effects between lower and higher doses is generally negligible, though higher doses may increase risk of gastrointestinal side effects 1, 6
- When combined with clavulanic acid, the maximum daily dose of amoxicillin may be limited by clavulanic acid-associated side effects rather than amoxicillin itself 6
Common Pitfalls
- Using first-generation cephalosporins instead of amoxicillin for conditions like Lyme disease, as they are ineffective against B. burgdorferi 1
- Underdosing amoxicillin when treating resistant S. pneumoniae, particularly during viral coinfection 5
- Failing to adjust dosing in patients with severe renal impairment 2
- Using unnecessarily high doses when lower doses would be effective, increasing the risk of side effects and antimicrobial resistance 3