Adverse events of metronidazole and amoxicillin: Retrospective analysis of a large data set of five randomized clinical trials

Aim To evaluate the frequency of side effects associated with intake of metronidazole (MTZ) + amoxicillin (AMX) in periodontal treatment, and to explore associations between these events and patients' features. Materials and Methods Data of five randomized clinical trials testing MTZ + AMX adjunctive to mechanical therapy were evaluated. Volunteers answered an adverse event questionnaire. Results Information from 656 subjects was assessed. The frequency of side effects in the antibiotic- and placebo-treated groups ranged from 1.0% to 17.7% and 0.9% to 13.7%, respectively. The events more frequently observed in the antibiotic than in the placebo group were diarrhoea and metallic taste (p < .05). Diabetes significantly raised the odds of a patient reporting discomfort (odds ratio [OR] = 2.6), diarrhoea (OR = 4.0), weakness (OR = 6.0) and excessive sleepiness (OR = 2.9). In systemically healthy volunteers, using antibiotics 3 months post-mechanical treatment (healing phase) (OR = 3.0), being a woman (OR = 3.9) and aged <= 49 (OR = 4.5) significantly increased the chances of reporting adverse events. Conclusions The occurrence of side effects during MTZ + AMX treatment ranged from uncommon (1%) to very common (17.7%). The main factors raising the chances of a patient reporting adverse events were diabetes and taking antibiotics in the healing phase, instead of in the active phase of treatment. Patients <= 49 years old and females also tend to report more side effects.