Pros and Cons of Extended-Release Antiepileptic Drugs

Weighing Your Options With Extended Release Meds

Extended-release (ER) preparations offer a means to decrease dosing frequency compared with immediate-release (IR) medications. In addition, ER preparations offer more consistent serum drug levels with higher troughs, which may protect against breakthrough seizures, and lower peaks, which may mitigate dose-related side effects.

ER formulations, which include controlled-release, delayed-release, modified-release, slow-release, and sustained-release preparations, aim to achieve more consistent serum drug levels. (For simplification, the term "ER" is used in this article to represent these different formulations.) ER preparations are available for many antiepileptic drugs (AEDs), including carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, topiramate, and valproate.^[4]

More than one ER formulation may be available for a given AED. For example, carbamazepine is available in two different ER formulations. Shire's Carbatrol® relies on Microtrol® technology that uses combinations of three different types of beads with different dissolution characteristics within a single capsule, whereas Novartis' Tegretol® XR uses tablets with an osmotic-release delivery system.

Although compliance may be enhanced by a once-a-day ER product, clinicians may hesitate to prescribe such preparations because the consequences of a missed dose may be more severe owing to the extended interval before the next dose.^[3] Pellock and Brittain^[4] recently addressed this issue in an industry-sponsored computer-modeling pharmacokinetics study. Defining "forgiveness" (F) as the "margin of therapeutic effect following a missed dose," the authors calculated F as the difference between duration of action (D) and dosing interval (I), or F = D – I.

Concentration/time curves were calculated for IR and ER formulations (called "XR" in their study). For both formulations, duration of action increased with larger doses. The duration of action was longer post-dose for ER than IR products, which tended to mitigate the drop in level from a missed dose.

The authors observed, "Compared with TID [three times daily] dosing of the IR formulation, the forgiveness interval was the same (XR_BID) or even longer (XR_qd) with the XR AEDs." They attributed this effect to the slower release rate and prolonged time of absorption of the ER product.