Abstracts

Rationale: Epilepsy is the most common neurological disorder requiring medical treatment during pregnancy, affecting 0.3-0.8% of pregnant women.1 Treatment must balance risk of seizures with potential for adverse effects from drug use on the exposed offspring.2 The use of new AEDs by fertile women with epilepsy has increased considerably; however, there is sparse information about many of these new AEDs regarding pregnancy.3 Perampanel (PER) is a selective, orally active, noncompetitive AMPA receptor antagonist approved in >40 countries, including the US and in the EU, for adjunctive treatment of partial seizures with or without secondarily generalized seizures in patients with epilepsy aged ≥12yrs and in Canada in patients aged ≥18yrs. There are no adequate and well-controlled studies specifically in pregnant women treated with PER. A review of pregnancies in the PER clinical studies has been compiled.Methods: Total safety database included data from epilepsy and nonepilepsy populations and healthy volunteers from phase 1 studies (Table 1). In epilepsy studies, enrolled participants were receiving 1–3 concomitant AEDs. Protocols required that female participants of childbearing potential have a negative pregnancy test before entering a study and agree to be abstinent or use ≥1 medically acceptable method of contraception (eg, double-barrier method, IUD, or vasectomized partner) throughout the study period. Urine pregnancy tests were administered to all subjects on a scheduled basis as part of protocol. Pregnancy was captured as a treatment-emergent adverse event and confirmed with urine and serum pregnancy tests.Results: As of 4/17/15, there have been 25 pregnancies in 22 women enrolled in all PER clinical studies (Table 1). The majority of pregnancies occurred in the open-label extension (OLE) of the phase 3 partial seizure studies. Of the pregnancies, 12 resulted in induced abortions, 5 resulted in spontaneous abortions, 5 resulted in the birth of a healthy infant, 1 resulted in a neonate death, and 2 subjects were lost to follow-up. Of the 5 healthy births, the number of days between the last menstrual period and the discontinuation of PER (days fetus could have possibly been exposed to PER and concomitant AEDs in utero) ranged from 22-107 (1 subject=22 days; 1 subject=39 days; 1 subject=57 days; and 1 subject=107 days; 1 subject=no information).Conclusions: There are no adequate and well-controlled studies of PER in pregnant women; therefore, the US PI notes that PER is a pregnancy category C agent based on available animal data. 25 total pregnancies occurred in all PER clinical studies (>5000 subjects) despite protocol requirements. Outcomes of most pregnancies were deemed by investigator to be unrelated to study drug. Physicians are encouraged to enroll pregnant patients on PER in the North American Antiepileptic Drug (NAAED) Pregnancy Registry in order to continue to provide more data and further characterize the profile of PER in pregnant women. 1Bech.BMJ2014;349:g5159 2Harden.Continuum2014;20:60 3Reimers.BMJ2014;23:585 Support: Eisai Inc.