Should Amoxicillin-Clavulanate Be Taken With Food?
Yes, amoxicillin-clavulanate should be taken at the start of a meal to minimize gastrointestinal side effects and enhance absorption of the clavulanate component. 1
Administration Guidance
The FDA label explicitly states that each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset. 1
While amoxicillin-clavulanate may be taken without regard to meals from an absorption standpoint, the absorption of clavulanate potassium is specifically enhanced when administered at the start of a meal. 1
Taking the medication at the start of a meal (rather than on an empty stomach) significantly reduces gastrointestinal side effects, particularly diarrhea, which is the most common and problematic adverse effect associated with clavulanate. 2
Clinical Rationale
The clavulanate component has reduced relative bioavailability when dosed 30 and 150 minutes after the start of a high-fat breakfast, supporting administration at the start of meals rather than after eating. 1
Gastrointestinal side effects become especially problematic when clavulanate doses exceed approximately 10 mg/kg per day, making food administration even more critical for tolerability. 2
Dosing three times daily is associated with significantly higher incidence of gastrointestinal side effects compared to twice-daily dosing, independent of food intake. 2
Common Pitfall to Avoid
Do not instruct patients to take amoxicillin-clavulanate on an empty stomach or between meals, as this increases the risk of nausea, diarrhea, and other gastrointestinal complaints that may lead to treatment discontinuation. 1
Patients should be counseled that if diarrhea is severe or lasts more than 2-3 days, they should contact their physician, as this may indicate Clostridium difficile infection. 1