Maximum Daily Dose of Clavulanate
The maximum daily dose of clavulanate for adults is 375 mg per day, typically administered as 125 mg three times daily or 125 mg twice daily depending on the formulation. 1
Adult Dosing Guidelines
The clavulanate component in amoxicillin-clavulanate formulations is standardized across different preparations, with specific maximum amounts:
- Standard adult formulations contain 125 mg of clavulanate per dose
- For twice-daily dosing: 125 mg × 2 = 250 mg clavulanate per day
- For three-times-daily dosing: 125 mg × 3 = 375 mg clavulanate per day
The FDA-approved labeling for amoxicillin-clavulanate clearly states that the maximum daily clavulanate dose should not exceed 375 mg in adults 1. This is important because while increasing the amoxicillin component may be beneficial for certain resistant pathogens, increasing clavulanate beyond this threshold does not provide additional clinical benefit and may increase gastrointestinal side effects.
Formulation Considerations
It's important to note that different formulations contain varying ratios of amoxicillin to clavulanate:
- 250/125 mg tablets (twice or three times daily)
- 500/125 mg tablets (twice or three times daily)
- 875/125 mg tablets (twice daily)
The FDA label specifically warns that two 250/125 mg tablets should not be substituted for one 500/125 mg tablet, as this would deliver excess clavulanate (250 mg vs 125 mg) 1.
Pediatric Dosing
For pediatric patients, clavulanate dosing is weight-based:
- Standard pediatric formulation: 6.4 mg/kg/day divided in two doses 2
- Maximum pediatric clavulanate dose: 10 mg/kg/day 3
The high-dose pediatric formulation (90/6.4 mg/kg/day of amoxicillin/clavulanate) was specifically designed to increase the amoxicillin component while maintaining the same clavulanate exposure to minimize gastrointestinal side effects 2.
Clinical Considerations
- Higher doses of clavulanate do not improve efficacy against resistant pathogens but do increase the risk of gastrointestinal side effects, particularly diarrhea 4
- When higher antibiotic potency is needed, increasing the amoxicillin component while maintaining the clavulanate at standard doses is the recommended approach 5
- Studies have shown that twice-daily formulations with reduced total daily clavulanate have improved gastrointestinal tolerability compared to three-times-daily regimens 4
Special Populations
For patients with renal impairment:
- No dose adjustment is needed for mild to moderate renal impairment
- For severe renal impairment (GFR <30 mL/min), the dose should be reduced or the dosing interval extended 1
- Patients on hemodialysis should receive doses every 24 hours plus an additional dose during and after dialysis 1
Remember that while the amoxicillin component may be increased for certain resistant pathogens (up to 4000 mg/day), the clavulanate component should remain at or below the maximum daily dose to minimize adverse effects while maintaining beta-lactamase inhibition.