Maximum Dose of Co-Amoxiclav for Adults with Normal Renal Function
For adults with normal renal function, the maximum oral dose of co-amoxiclav is 875 mg amoxicillin/125 mg clavulanic acid every 8 hours (total daily dose: 2625 mg amoxicillin/375 mg clavulanic acid), or alternatively 2000 mg amoxicillin/125 mg clavulanic acid every 12 hours (total daily dose: 4000 mg amoxicillin/250 mg clavulanic acid) for severe or resistant infections. 1
Standard Dosing Regimens
Moderate Infections
- Standard dose: 500 mg/125 mg every 12 hours or 250 mg/125 mg every 8 hours for most community-acquired infections 1
- This regimen provides adequate coverage for typical respiratory and soft tissue infections without resistance risk factors 2
Severe Infections and Respiratory Tract Involvement
- High-dose regimen: 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours 1
- This is the FDA-approved maximum for standard formulations in adults with normal renal function 1
Maximum High-Dose Regimen (Resistant Pathogens)
- Extended-release maximum: 2000 mg/125 mg twice daily (total 4000 mg amoxicillin/250 mg clavulanic acid daily) 3, 4
- This achieves 90-92% predicted clinical efficacy against penicillin-resistant Streptococcus pneumoniae with MICs up to 4-8 mg/L 3
- Indicated when antibiotic resistance is likely: recent antibiotic use (past 4-6 weeks), age >65 years, healthcare exposure, treatment failure, or community resistance prevalence >10% 3, 4
Critical Dosing Considerations
Clavulanic Acid Limitation
- The clavulanic acid component is restricted to 125 mg per dose (maximum 375 mg daily in divided doses) due to gastrointestinal tolerability issues 1, 5
- Two 250 mg/125 mg tablets should never be substituted for one 500 mg/125 mg tablet, as this doubles the clavulanic acid dose and increases adverse effects 1
- Gastrointestinal adverse events (nausea, vomiting, diarrhea) occur in 15-40% of patients, with higher rates at increased clavulanic acid doses 3, 6
Administration Timing
- Take at the start of meals to enhance clavulanic acid absorption and minimize gastrointestinal intolerance 1
- May be taken without regard to meals, but meal-time administration is preferred 1
Special Clinical Scenarios
Severe ESBL Infections (Off-Label High-Dose)
- Research suggests maximal therapeutic doses up to 2875 mg amoxicillin twice daily with 125 mg clavulanic acid may break resistance in select ESBL-producing Klebsiella pneumoniae urinary tract infections 7
- This exceeds standard FDA-approved dosing and should only be considered in consultation with infectious disease specialists for recurrent infections failing carbapenem therapy 7
Intravenous Maximum Dose
- IV formulation: 1200 mg (1000 mg amoxicillin/200 mg clavulanic acid) every 6-8 hours for severe infections 3
- For critically ill patients or those with augmented renal clearance, doses up to 2200 mg every 6-8 hours have been studied 8
Common Prescribing Pitfalls
Avoid These Errors
- Do not exceed 4000 mg/day of amoxicillin component in standard practice 4
- Do not exceed 375 mg/day of clavulanic acid in divided doses to prevent dose-related diarrhea 1, 6
- Do not use 875 mg/125 mg formulation in patients with GFR <30 mL/min—this dose is contraindicated in severe renal impairment 1
- Patients weighing ≥40 kg should receive adult dosing, not pediatric weight-based calculations 3
Reassessment Timeline
- Evaluate clinical response at 48-72 hours; lack of improvement warrants dose escalation to high-dose regimen or alternative therapy 3
- For respiratory infections, if no improvement after 3-5 days on standard dosing, switch to high-dose amoxicillin-clavulanate or respiratory fluoroquinolone 4
Duration of Therapy
- Respiratory infections: 5-7 days (as effective as 10 days with fewer adverse events) 3, 4
- Sinusitis: 5-7 days for adults, 10-14 days for children 3, 4
- Urinary tract infections: 3-7 days for uncomplicated cases 3
- Community-acquired pneumonia: 7-10 days, may extend to 14 days based on clinical response 3