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


Gregory Krauss MD, Johns Hopkins University School of Medicine, Meyer 2-147, 600 N Wolfe St, Baltimore, MD 21287, USA
Tel.: 410-955-2822
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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.