ARTICLE : GENERIC AND BRAND NAME AEDS – CONSIDERATIONS FOR CLINICIANS AND PATIENTS
Issues for Generics Specific to Epilepsy
The characteristics of epilepsy and the potential serious ramifications of therapy failure must be considered. Epilepsy is not like other medical conditions, such as elevated cholesterol, because of the seriousness of seizure events. Epilepsy patients are particularly vulnerable to the disadvantages of generic products, since slight deviations in the serum concentrations of AEDs can be the difference between keeping a patient seizure free and the occurrence of a breakthrough seizure. A breakthrough seizure after a long remission can have significant psychosocial and physical consequences for the epilepsy patient in areas of life such as employment and driving, and could lead to injury.
Antiepileptic drugs have a high potential for central nervous system-related adverse events. This is usually related to the serum concentration of the drug. Some AEDs have narrow a therapeutic index, which is defined by the FDA as less than a two-fold difference between the minimum toxic concentration and the minimum effective concentration. Carbamazepine, phenytoin, and sodium valproate in particular have narrow therapeutic indices. Individual patients may have an even narrower difference between efficacy and toxicity.
The rate and extent of absorption or bioavailability often differs between different generic versions of branded products, and each differs from the branded formulation itself. Changes in the bioavailability of an AED in a particular patient can have serious effects for that patient.
Titration is particularly important when treating a patient with AEDs. Management regimens may become very complex, with titration sometimes taking weeks in order to avoid adverse effects. Patients need their medication to be consistent during titration so that prescribed changes of dose have predictable consequences. During the titration period, if there is a switch to a generic or if one generic is changed to another when a prescription is refilled, there is a potential for a change in seizure control. In addition, AEDs must be managed to account for drug interactions with other medications, such as hormonal contraceptives. A change in serum concentration of one drug may lead to changes in serum concentrations of co-medications.
Generics are susceptible to changes over time. Excipients and colorants used in generic products may differ from the brand, potentially causing problems. In 2000, there were more than 26 different generic preparations for five brand name AEDs, with multiple suppliers and formulations. 3 Pharmacies may change supplier depending on price and availability. For reasons discussed above, it is desirable for physicians to be able to use a single-source generic during initiation, titration, and maintenance of AED therapy; however, patients and physicians generally do not have any indication of a change from one refill to another unless they specifically ask. Patients can also become confused by changes in their medication. Generic names are not as easy to remember, spell, or pronounce as branded names. In addition, generic products usually differ in appearance from the brand and from other generic versions of the same product.
Generics are substituted for branded medicines as a cost-saving measure. Yet the savings associated with a generic may be offset by costs associated with office visits, lab tests, emergency room visits, or hospitalizations when the generic provokes seizures or adverse effects.
