Intranasal Diazepam FDA Approved for Seizure Clusters

January 13, 2020

The drug, which is a schedule IV controlled substance, is the first nasal spray approved as rescue medication in patients 6 years and older with epilepsy.

Jacqueline A. French, MD

The US FDA has approved intranasal diazepam (Valtoco; Neurelis) for the treatment of acute, intermittent, stereotypic episodes of frequent seizure activity, otherwise known as seizure clusters or acute repetitive seizures.1

The drug, which is a schedule IV controlled substance, is the first intranasal rescue formulation approved for patients age 6 and older. Notably, the FDA has granted the drug 7 years of Orphan Drug Exclusivity.

An interim analysis of data from the phase 3 open-label study showed a good safety and tolerability profile consistent with what is expected for diazepam, regardless of usage frequency. The results, which were presented at the 2019 American Epilepsy Society Annual Meeting, December 6-10, in Baltimore, Maryland, demonstrated no trends for usage frequency effects on clinical or laboratory parameters, as well as olfactory changes.2

“In the past, [there have been agents] that have burned the inside of the nose, so you lost your sense of smell. To know that it doesn’t happen with this therapy is essential,” said Jacqueline A. French, MD, professor of neurology at NYU Langone Medical Center, in an interview with NeurologyLive.

WATCH: Jacqueline A. French, MD: Improving Rescue Treatment With Intranasal Diazepam

Valtoco consists of a proprietary formulation of diazepam that is delivered via the Intravail system, which enables the noninvasive delivery and transmucosal absorption of the drug.

“Intranasal medications used during the preictal state pose several advantages over rectal diazepam, which until recently was the only FDA-approved emergency therapy available. It is likely that that medication would be administered faster, especially for patients who have adult weight and habitus,” Eric Segal, MD, co-director of Epileptology, Hackensack Meridian Health, told NeurologyLive. “Additionally, many adult patients only used oral benzodiazepines instead of the approved rectal. With less stigma associated with a nasal formulation, it is likely that more patients will have emergency medications readily available. Faster access and availability will hopefully prevent the potential sequel associated with seizures.”

Notable safety information includes the risk for profound sedation, respiratory depression, coma, and death with concomitant use of benzodiazepines and opioids. In the case of necessary concomitant use, healthcare providers should limit the dose and duration of treatment to the minimum required, and closely monitor patients for signs of respiratory depression and sedation. The drug is also contraindicated in patients with a known sensitivity to diazepam and those with acute narrow-angle glaucoma.

The most common adverse events associated with intranasal diazepam include somnolence, headache, and nasal discomfort. Healthcare providers and patients should be aware that use of benzodiazepines may exacerbate glaucoma and may be associated with central nervous system depression; as such, patients should wait until symptoms have subsided before operating machinery, driving a car, or riding a bicycle. The drug manufacturer also notes that Valtoco should not be used in neonates or infants, as adverse events, including “gasping syndrome,” can occur in these patients who are exposed to benzyl alcohol-preserving drugs.

REFERENCES

1. Neurelis Announces FDA Approval for Seizure Rescue Treatment VALTOCO® (Diazepam Nasal Spray) that Incorporates the Science of Intravail® for Consistent and Reliable Absorption [news release]. San Diego, CA: Neurelis Inc. January 13, 2020. prnewswire.com/news-releases/neurelis-announces-fda-approval-for-seizure-rescue-treatment-valtoco-diazepam-nasal-spray-that-incorporates-the-science-of-intravail-for-consistent-and-reliable-absorption-300985345.html. Accessed January 13, 2020.

2. Miller I, Wheless JW, Hogan RE, et al. Safety and tolerability of NRL-1, an intranasal formulation of diazepam, in relationship to usage frequency in subjects with epilepsy: interim results from a phase 3, open-label, repeat dose study. Presented at: 2019 American Epilepsy Society Annual Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 1.22.