Introduction: Phenobarbital is one of the drugs most used in the treatment of epilepsy, with different formulations available on the market today. Objectives: The objective of this study was to evaluate the effect of interchangeability on the profile of the adverse effect, on quality of life and on plasma concentrations before and after the exchange of phenobarbital formulations in patients with epilepsy. Methods: This is a before and after study, in which adult patients with a diagnosis of epilepsy were included in outpatient treatment with phenobarbital. The Adverse Events Profile (AEP) and Quality of Life in Epilepsy-31 (QOLIE) questionnaires were applied before and after the brand change in phenobarbital, as well as the determination of the plasma concentration of phenobarbital. In the first meeting, the “Interchangeable Pharmaceutical Product in the Treatment of Epilepsy” questionnaire was also applied. Physical-chemical tests to evaluate the quality of the tablets were performed according to the parameters of the Brazilian pharmacopoeia. Results: The population was composed of eight patients; six were females, with a mean age of 51.4 (SD=5.4) years old and four did not have a full first degree. Of the interviewees, six had no knowledge of the three types of existing antiepileptic formulations. Significant differences were found for the “Emotional wellbeing” domain of quality of life before and after the formulation change (p=0.016) and no significant difference between frequencies of adverse effects and plasma concentrations. Conclusion: The results suggest the importance of pharmacovigilance, in addition to being able to subsidize new clinical studies regarding the interchangeability between antiepileptics. In addition, the physical-chemical tests point to the need to strengthen health surveillance actions.