Improved CNS tolerability following conversion from immediate-to extended-release carbamazepine

Objectives - Tolerability of 'narrow therapeutic ratio' (NTR) antiepileptic drugs may improve with uniform drug delivery. We determined whether conversion from immediate-release carbamazepine (IR-CBZ) to extended-release carbamazepine (ER-CBZ) decreased the incidence of CNS side-effects associated with drug concentration oscillations. Methods - We compared CNS side effects and seizure frequency for patients with partial-onset seizures (n = 61) treated with IR-CBZ for ≥1 year with conversion to ER-CBZ for ≥1 year. We compared tolerability findings with absorption variability of the formulations. Results - Incidence of CNS side-effects decreased from 49% during IR-CBZ treatment to 20% following conversion to ER-CBZ. Patients also had improved tolerability of high doses (≥1200 mg/day) during ER-CBZ treatment. Pharmacokinetic analysis showed absorption and drug concentration were much more variable for the immediate-release formulation. Conclusions - This study suggests that ER-CBZ formulations, with smoother drug delivery and less variable absorption, provide improved CNS tolerability compared with immediate-release formulations.