Will 875-125 mg Amoxicillin-Clavulanate Three Times Daily Work?
No, taking 875-125 mg amoxicillin-clavulanate three times daily is not an FDA-approved dosing regimen and would result in excessive clavulanate exposure, significantly increasing your risk of gastrointestinal side effects, particularly severe diarrhea. 1
FDA-Approved Dosing for 875-125 mg Tablets
The 875-125 mg formulation is specifically designed and approved for twice-daily dosing only 1:
- Standard adult dose: One 875-125 mg tablet every 12 hours for more severe infections and respiratory tract infections 1
- This twice-daily regimen provides adequate coverage for respiratory infections including community-acquired pneumonia, acute bacterial rhinosinusitis, and acute exacerbations of chronic bronchitis 2
- Treatment duration is typically 5-14 days depending on the specific infection 2, 3
Why Three Times Daily Dosing with 875 mg Tablets Is Problematic
Clavulanate overdosing: Taking 875-125 mg three times daily would give you 375 mg of clavulanate per day (125 mg × 3), which is 50% higher than the maximum recommended daily clavulanate dose 1:
- The FDA explicitly warns against substituting formulations because different tablet strengths contain different amounts of clavulanate 1
- Excessive clavulanate significantly increases the risk of diarrhea and gastrointestinal intolerance 1, 4
- In clinical trials, higher clavulanate doses resulted in statistically significant increases in severe diarrhea (2% vs 1%) and treatment withdrawals 1
Correct Three-Times-Daily Regimen (If Needed)
If three-times-daily dosing is clinically indicated for your infection, you should use the 500-125 mg tablet instead 1:
- Correct dose: One 500-125 mg tablet every 8 hours 1
- This provides 375 mg total daily clavulanate, which is the appropriate amount for three-times-daily dosing 1
- Clinical trials demonstrate equivalent efficacy between 875-125 mg twice daily and 500-125 mg three times daily for respiratory and urinary tract infections 1, 5, 6
Clinical Evidence Supporting Twice-Daily Dosing
The 875-125 mg twice-daily regimen has been extensively validated 1, 5, 6:
- In pivotal FDA trials with 1,191 patients, the 875-125 mg every 12 hours regimen showed comparable efficacy to 500-125 mg every 8 hours for lower respiratory tract infections and complicated urinary tract infections 1
- Clinical cure rates were equivalent (81% vs 80% at 2-4 days post-therapy) 1
- The twice-daily regimen had significantly less severe diarrhea (1% vs 2%, p<0.05) 1
- For community-acquired pneumonia, clinical success rates were 91.5-93% with twice-daily dosing 5
Specific Infection-Based Recommendations
For respiratory infections (sinusitis, bronchitis, pneumonia): Use 875-125 mg twice daily for 7-14 days 7, 2, 8
For skin/soft tissue infections: Use 875-125 mg twice daily for 7-10 days 2, 3
For chronic rhinosinusitis: Studies used 625 mg (500 mg amoxicillin component) three times daily, not 875 mg three times daily 7
Critical Safety Considerations
- Never substitute two 250-125 mg tablets for one 500-125 mg tablet because this doubles the clavulanate dose 1
- Take at the start of meals to minimize gastrointestinal side effects and enhance clavulanate absorption 1
- If you have renal impairment with GFR <30 mL/min, you should not use the 875-125 mg dose at all 1
Bottom line: Use your 875-125 mg tablets twice daily (every 12 hours), not three times daily. If your healthcare provider specifically wants three-times-daily dosing, you need to obtain 500-125 mg tablets instead.