Abstracts

To assess whether a switch from a brand name antiepileptic drug (AED) to a generic AED, or from a generic AED to another generic AED results in breakthrough seizures or adverse events. According to the FDA, generic drugs must be bioequivalent to brand name AEDs, defined as no less than 80% and no more than 125% average maximum plasma concentrations. Controversy exists whether AEDs, which have a narrow therapeutic range, are interchangeable with brand name drugs with respect to seizure control and adverse effects. The literature contains reports of breakthrough seizures and adverse events after generic substitution, but the extent of these occurrences is unknown. We designed a 13 question survey for neurologists in order to evaluate whether breakthrough seizures and/or adverse events had occurred during the past year among epilepsy patients who were switched to a generic AED from a brand name AED, or from one generic AED to another generic AED. Other survey questions included the proportion of patients in the practice with epilepsy, geographic practice location, type of patient insurance, and consequences of breakthrough seizures or adverse events, if they occurred. The survey was mailed on 7/11/03 to 6,420 US neurologists, whose names and addresses were obtained from a list broker. The estimated time of completion of the survey was 5 minutes. No compensation or honoraria was offered for completion of the survey. The last date of acceptance of results was 8/25/03. Three hundred and one neurologists responded (4.7%). One hundred and ninety-six neurologists (68%) reported breakthrough seizures and 162 (56%) reported increased side effects attributable to a switch from a brand name to a generic AED in the past year. Ninety-four neurologists (33%) reported breakthrough seizures and 76 (27%) reported increased side effects attributable to a switch from one generic to another generic AED. Six percent of neurologists reported 1 patient, 47% reported 2-4 patients, and 28% reported 5 or more patients suffering from breakthrough seizures or increased side effects. In order to treat the consequences of generic drug substitution, 188 neurologists reported the need for phone consultations, 166 extra office visits, 128 emergency room visits, and 46 hospital admissions. Seventy-seven neurologists reported that patients missed work, 25 indicated that the doctor patient relationship was undermined, and 23 reported patient injury.
Figure 1: Hyperintense DWI pattern after status epilepticus (right temporoparietal and pulvinar hyperintensities) More than two thirds of neurologists who responded to this survey reported breakthrough seizures, and more than half observed increased side effects due to generic substitution of brand name AEDs in the past year. Consequences included additional phone consultations, office visits, emergency room visits, hospitalizations, loss of work, patient injury, and deterioration of the doctor patient relationship. Physicians should carefully weigh the cost/benefit ratio of switching to generic from brand name AEDs or generic to generic AEDs in patients with epilepsy. (Supported by Shire, US)