Extended-release formulations of antiepileptic drugs: rationale and comparative value

Abstract

Extended-release products are designed to prolong the absorption of drugs with short half-lives, thereby allowing longer dosing intervals while minimizing fluctuations in serum drug levels. The relationship between serum drug concentration and clinical effects of antiepileptic drugs (AEDs) can be complex and reducing fluctuations in serum drug levels is not equally advantageous for all AEDs. Extended-release formulations have been shown to be particularly valuable for carbamazepine, whereas for other AEDs advantages, other than prolongation of the dosing interval, have not been clearly demonstrated. Differences in bioavailability may exist between extended-release and immediate-release formulations and among different brands of extended-release products. Therefore, when switching from one formulation to another, careful monitoring of clinical response and attention to the need for dose adjustment are warranted.

FIGURE 1

Comparative effectiveness of lamotrigine and carbamazepine (expressed as the percentage of patients retained in the trial at the end of the assessment period) in two randomized, double-blind trials among patients aged 65 years or older with new-onset epilepsy. Duration of follow-up was 24 weeks in trial A and 40 weeks in trial B. The two trials had a very similar design and identical twice-daily dosing regimens, but carbamazepine was administered in an immediate-release (IR) formulation in trial A and in extended-release (ER) formulation in trial B. Abbreviations: IR, immediate release; ER, extended release; N, number of subjects in the intent-to-treat population. References:*39, ^†40.