Improved CNS tolerability following conversion from immediate- to extended-release carbamazepine.
OBJECTIVE
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 > or =1 year with conversion to ER-CBZ for > or =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 (> or =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.
Miller
A D
AD
Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Krauss
G L
GL
Hamzeh
F M
FM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D002220:Carbamazepine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D002220:Carbamazepine