Safety and Equivalency of Buccal Film Formulation of Diazepam in Peri-ictal and Interictal Periods
In results presented at the American Epilepsy Society (AES) Annual Meeting in New Orleans, LA, bioavailability and safe administration of a buccal film formulation of 12.5 mg diazepam (Aquestive, Warren, NJ) were demonstrated to be equal during both periods without seizure (ie, interictal) and during or within 5 minutes of seizure (peri-ictal). The rate of adverse events was low; adverse events included somnolence (5.7%) and dizziness, nausea, numbness, and oral tingling (2.9% each).
This formulation of diazepam is a film that is placed on the inner cheek that has the potential to be the first orally-available formulation. Diazepam is approved as rescue treatment for patients with acute repetitive seizures (ARS), also known as seizure clusters in patients with medically refractory epilepsy. It is estimated that 30% to 40% of patients with epilepsy have seizures that are medically refractory to treatment, and the only rescue therapy currently available is a rectal gel formulations. It is expected that having an oral formulation may provide options that will increase adherence to treatment, particularly for adults when they are outside their homes.
In this study, patients age 17 to 65 years with poorly controlled focal or tonic-clonic seizures who had at least 1 seizure every 3 days or at least 10 seizures per month (n = 35) were treated peri-ictally while admitted to an epilepsy monitoring unit and interictally when they had not had a seizure within the last 3 hours on an outpatient basis (remained in clinic for 8 hrs postadministration). All subjects received both treatments and plasma diazepam levels were measured at 0.25, 0.5, 1, 1.5, 2, and 4 hours after administration. The 2 different drug administrations were separated by 2 to 3 weeks.