A review of a diazepam nasal spray for the treatment of acute seizure clusters and prolonged seizures

ABSTRACT

Introduction

Some people with epilepsy experience acute repetitive seizures (ARS), also termed seizure clusters, which have a negative impact on patient and caregiver quality of life, emotional wellbeing, daily function, and may pose risk of injury or death. In addition, these events increase healthcare utilization in emergency departments and hospitals, which might be avoided with use of an at-home rescue medication. Intranasal formulations of benzodiazepines used as rescue medications provide a means of delivering rescue medication that is socially acceptable and more easily administered than rectal drug.

Areas covered

This article provides a review of intranasal diazepam covering development, pharmacokinetics, dosing, safety, adverse effects, and efficacy. The authors compare it with rectal diazepam and intranasal midazolam.

Expert opinion

Intranasal rescue drugs are a valuable treatment modality for seizure clusters and prolonged seizures that are effective and well tolerated with the potential to enhance patient quality of life, reduce the incidence of seizure-related injury, and lessen the need for hospital visits. The literature does not provide evidence comparing the various rescue agents, and head-to-head comparison studies are needed. An inhaled benzodiazepine as a seizure rescue drug is currently undergoing clinical trials.

KEYWORDS:

• Intranasal
• diazepam
• rescue medication
• acute repetitive seizures
• seizure cluster

Article highlights

• Patients with refractory epilepsy who experience seizure clusters benefit from having a rescue medication to abort subsequent seizures once a cluster has begun and avoid hospitalization.

• Until recently, rectal diazepam was the main formulation of rescue benzodiazepine that was not an oral pill.

• The FDA approved version nasal diazepam has demonstrated similar bioavailability as the rectal formulation.

• Nasal diazepam is overall well tolerated by patients and no serious adverse effects were reported.

• Direct comparisions in efficacy between nasal diazepam and midazolam have yet to occur, but a notable difference is nasal diazepam is approved for ages 6 and older compared to 12 and older for nasal midazolam.

Declaration of interest

M Sperling has received compensation for speaking at CME programs from Neurology Live, Medscape, Projects for Knowledge, international Medical Press, Eisai, and UCB pharma. He is an advisor for scientific publications for Neurelis. He consults for Medtronic with payments to Thomas Jefferson University. He has received research support from Eisai; Medtronic; Neurelis; SK Life Science; Takeda; Xenon; Cerevel; UCB pharma; and Engage Pharmaceuticals. He has received royalties from Oxford University press. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.