FDA Sends CRL For Diazepam, Insomnia Linked to Cognitive Impairment, Midazolam Underutilized By EMS


Neurology News Network for the week ending October 2, 2020.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

The FDA has sent a complete response letter to Aquestive Therapeutics for its new drug application for diazepam buccal film for the management of seizure clusters. The agency indicated that certain weight groups in a study that was part of the NDA showed a lower drug exposure level than what was desired. Aquestive noted in a release that it plans to provide the FDA with additional information on pharmacokinetic modeling in order to demonstrate that the desired levels of exposure can be achieved with dose adjustments. Additionally, the regulatory agency stated that a small number of deviations from protocol were identified in blood draws in 1 of the studies included. No other safety, clinical, or Chemistry, Manufacturing and Control issues were identified in the CRL, and no further clinical studies are anticipated as necessary to complete the resubmission for the therapy

Data from an analysis of the Penn State Adult Cohort suggest that insomnia accompanied by objective short sleep duration is linked to an increased prevalence of cognitive impairment, particularly as it relates to cardiometabolic health. All told, those who reported poor sleep or chronic insomnia who slept for fewer than 6 hours were twice as likely to have cognitive impairment and possible vascular cognitive impairment compared with those who slept more than 6 hours. Julio Fernandez-Mendoza, clinician scientist, Penn State Hershey Sleep Research & Treatment Center told NeurologyLive. “These data are among the first to indicate that patients who complain of insomnia and who sleep objectively short in the lab have a higher prevalence of mild cognitive impairment, particularly that associated with cardiometabolic risk factors. From a practice standpoint, patients with insomnia who have cardiometabolic risk factors should be objectively evaluated for their nighttime sleep and cognition, and not just evaluated by self-reports.

A cross-sectional analysis examining the use of midazolam by an emergency medical services agency for treatment of adults with status epilepticus showed a significant deviation from evidence-based benzodiazepine use, contributing to the need for rescue therapy and respiratory support. In total, 2494 cases of status epilepticus in adults were included in the analysis, with 1537 patients given midazolam at any dose (39.4% given 5 mg or more), yielding an administration rate of 62%. Led by Elan L. Guterman, MD, neurologist, University of California San Francisco, the data showed that undertreatment with midazolam was associated with an increased need for rescue therapy, with 282 (18%) patients needing a second dose. Those who received rescue therapy were less likely to have received an initial midazolam dose of 5 mg or more, had lower Glasgow Coma Scale (GCS) scores, and were evaluated by providers who had seen a higher number of patients with status epilepticus during the study period.

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