Abstracts

Rationale: To present a case series on the increase of breakthrough seizures associated with switching from branded to generic levetiracetam. Methods: We report a small cluster of increased incidence of seizures with generic substitution of levetiracetam (LEV). Five patients self-reported to their neurologist at an ambulatory epilepsy center an increase in seizure activity after switching from brand name LEV to generic formulations. While the adverse events were reported in the time frame of April to May 2009, the increase in seizures had occurred from November 2008 to April 2009 resulting in increased physician office visits, emergency room and hospital admissions. To confirm the timeline of increased seizure activity with generic use and to appropriately report these adverse events to the FDA, a call was made to each patient's pharmacy to collect dispensing dates, information regarding the generic's manufacturer dispensed, and lot numbers. The reporting pharmacist did a subsequent chart review to submit these adverse events to the FDA's Adverse Event Reporting Program (MedWatch). The MedWatch program is dependent on voluntary reporting from healthcare professionals and consumers. A convenience of the MedWatch program is the allowance for submissions via prepaid postal service envelope, phone, fax, and internet. Reports are not difficult to complete and can be submittted in less than 30 minutes, though many physicans and pharmacists fail to follow-up on adverse event reporting to the FDA. Mylan Pharmaceutical received FDA approval in November 2008 to manufacture the generic formulation of LEV tablets. And while all 5 of our patients were taking the Mylan formulation, to date there are 18 applicants listed in the FDA Orange Book to manufacture generic tablets. A review of the current literature via a MEDLINE search did not identify any case studies, abstracts, or research publications reporting this adverse event with generic LEV. Results: Subsequent to the increase in seizure frequency with generic LEV, all 5 patients returned to the brand name formulation and returned to baseline seizure control. Conclusions: These 5 patients demonstrate the need to revisit the FDA's regulations regarding therapeutic equivalence for generic formulations of antiepileptic drugs (AEDs). Breakthrough seizures not only affect a patient's quality of life, e.g. revocation of a driver's license, social stigma, loss of productivity, but in addition breakthrough seizures also contribute to the growing costs of health care for the patient and patient assistance programs. MedWatch reporting is easily accessible to consumers, physicians, and pharmacists. After identification of an adverse event, physician office support staff could also complete the data collection and MedWatch forms. Many consumers are unaware such a reporting system exists or that consumers can file an adverse event.