Amoxicillin Dosing: 1000mg Daily vs 850mg Twice Daily
When the calculated dose exceeds 1000mg, you should NOT give 1000mg once daily—instead, give the full dose divided into twice-daily or three-times-daily administration, as guideline-recommended regimens consistently use divided dosing for amoxicillin to maintain therapeutic serum levels throughout the day. 1, 2, 3
Why Divided Dosing is Essential
Amoxicillin's pharmacokinetics require divided dosing for optimal efficacy. The standard adult dosing regimens across all major guidelines consistently recommend divided doses rather than once-daily administration for therapeutic purposes:
- For H. pylori eradication: 1000mg twice daily (total 2000mg/day) is the standard recommendation 1, 3
- For Lyme disease: 500mg three times daily (total 1500mg/day) is recommended 1
- For respiratory and skin infections: Either 500mg three times daily or 875mg twice daily depending on severity 2, 3
The Problem with Once-Daily Dosing Above 1000mg
There is no evidence supporting once-daily amoxicillin dosing for therapeutic purposes in adults, and the FDA label explicitly does not recommend this approach. 3 The only exception is a single 1000mg once-daily regimen specifically validated for streptococcal pharyngitis, but this is the maximum recommended once-daily dose. 2
Absorption limitations make higher once-daily doses ineffective. Amoxicillin absorption from the gastrointestinal tract is saturable—giving more than approximately 1000mg at once does not proportionally increase serum levels and wastes medication. 4, 5
Correct Approach When Dose Exceeds 1000mg
If your calculated dose is above 1000mg daily, divide it appropriately:
- For doses of 1500mg/day: Give 500mg three times daily 1, 3
- For doses of 1750mg/day: Give 875mg twice daily 2, 3
- For doses of 2000mg/day: Give 1000mg twice daily 1, 3
Clinical Rationale
Divided dosing maintains therapeutic serum concentrations throughout the dosing interval. Studies demonstrate that serum levels remain substantially higher than the MIC for target organisms for 6 hours after a 2000mg dose, but this doesn't extend to 24 hours. 5 Therefore, maintaining coverage requires redosing every 8-12 hours depending on the total daily dose and infection severity.
Compliance concerns favor twice-daily over three-times-daily regimens when clinically appropriate. Electronic monitoring studies show dose-taking compliance of 79% for once-daily, 69% for twice-daily, 65% for three-times-daily, and 51% for four-times-daily regimens. 6 When choosing between 500mg TID and 875mg BID for similar total daily doses, the twice-daily regimen offers better compliance without sacrificing efficacy. 2, 6
Common Pitfall to Avoid
Never substitute two 250mg tablets for one 500mg tablet when using amoxicillin-clavulanate combinations, as this results in excessive clavulanate dosing and increased gastrointestinal side effects. 2 This warning applies specifically to combination products, not plain amoxicillin, but highlights the importance of using appropriate formulations and dosing schedules.