Generic Drug Switch in Epilepsy – Pharmacokinetic and Clinical Aspects

Background and aim: Generic drugs contain the same active ingredients as brand- name drugs, with the advantage of much lower costs. The aim of this thesis was to contribute new knowledge to the ongoing debate on the safety of generic antiseizure drug (ASD) substitutions. There was a particular emphasis on the pharmacokinetic and clinical outcomes.

Methods: In papers I and II, a prospective naturalistic study of generic drug switching of levetiracetam (LEV) was conducted with repeated LEV serum concentration measurements and assessment of quality of life before and after the switch. In paper III, a cross-sectional survey study was conducted to explore associations between the characteristics of people with epilepsy (PWE) and their attitudes toward the generic substitution of ASDs. In paper IV, an online survey study of physicians’ perspectives on generic ASD substitution in epilepsy was conducted.

Results: Paper I: Fluctuation of LEV serum concentrations was equal with branded LEV and the generic LEV. Within-subject variability was much larger than the small, non-significant differences between the two LEV products. No switchbacks occurred. Paper II: Irrespective of brand or generic treatment, subjects were less worried about seizures at the end of the study compared to at inclusion. Paper III: High proportions of PWE express concerns about generic substitution of ASDs. Survey respondents with prior experience of generic ASD substitution were more likely to accept a future switch. Paper IV: Neurologists in two major Swedish healthcare regions generally have positive attitudes toward the generic substitution of ASDs in epilepsy.

Conclusions: Current evidence suggests that the pharmacokinetic consequences of generic substitutions of bioequivalent immediate release second-generation ASDs are negligible at group level. Data on clinical aspects of generic substitutions are not as robust, but real-world prospective data indicate that possible substitution risks are generally small to non-existent in treatment-adherent individuals. Future studies should elaborate on interventions to ensure treatment adherence and reduce worries in connection with a switch. A structured nurse-led follow-up could be a cost-effective example of such an intervention that could facilitate successful generic substitution and lead to substantial cost savings.