Maximum Dose of Co-Amoxiclav
For adults with normal renal function, the maximum recommended dose of co-amoxiclav is 875 mg amoxicillin/125 mg clavulanate every 8 hours (total daily dose: 2625 mg amoxicillin/375 mg clavulanate), or alternatively 2000 mg amoxicillin/125 mg clavulanate every 12 hours (total daily dose: 4000 mg amoxicillin/250 mg clavulanate) for severe respiratory tract infections. 1
Standard Adult Dosing Framework
The FDA-approved dosing for adults varies by infection severity 1:
- Standard infections: 500 mg/125 mg every 12 hours or 250 mg/125 mg every 8 hours 1
- Severe infections and respiratory tract infections: 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours 1
High-Dose Formulation for Resistant Pathogens
For community-acquired pneumonia with suspected resistant organisms (particularly penicillin-resistant Streptococcus pneumoniae with amoxicillin MICs ≥4 mg/L), the pharmacokinetically enhanced formulation of 2000 mg/125 mg twice daily represents the highest validated dosing regimen. 2
- This high-dose regimen achieved 94.7% clinical success in treating community-acquired pneumonia 2
- Successfully eradicated penicillin-resistant S. pneumoniae in 3/3 patients with amoxicillin MICs of 8 mg/L 2
- The twice-daily 2000/125 mg regimen is associated with significantly less diarrhea compared to three-times-daily dosing 1
Critical Dosing Considerations
The 875 mg/125 mg every 12 hours regimen causes significantly less severe diarrhea and fewer withdrawals compared to 500 mg/125 mg every 8 hours, making it preferable when both are clinically appropriate. 1
Important Formulation Warnings
- The 250 mg/125 mg tablet contains 125 mg clavulanate, while the 250 mg/62.5 mg chewable tablet contains only 62.5 mg clavulanate—these are not interchangeable 1
- Different amoxicillin-to-clavulanate ratios mean tablets cannot be substituted for each other 1
Special Population Adjustments
For patients with hepatic impairment, dose with caution and monitor hepatic function at regular intervals. 1
For pediatric patients ≥40 kg, use adult dosing recommendations. 1
Infection-Specific Maximum Dosing
For severe infections requiring optimal pharmacodynamic coverage:
- Melioidosis: Co-amoxiclav 1750 mg/250 mg every 4-6 hours is required to achieve adequate time above MIC (T>MIC ≥90% in 95.8% of patients at 4-hour intervals vs only 10.8% at 12-hour intervals) 3
- Community-acquired pneumonia: 2000 mg/125 mg every 12 hours for 7-10 days 2
- Mild-moderate community-acquired pneumonia: 625 mg three times daily for 5 days may be sufficient in 76% of outpatients 4
Common Pitfall to Avoid
Do not exceed 2000 mg amoxicillin per dose or 4000 mg amoxicillin per day in standard practice, as these represent the upper limits validated in clinical trials for safety and efficacy. 1, 2 Higher doses have not been studied for safety and may increase risk of adverse effects without proven additional benefit.