Concomitant cannabidiol does not impact safety and effectiveness of diazepam nasal spray for seizure clusters: Post hoc analysis of a phase 3 safety study

Jurriaan M Peters; Vinay Puri; Eric Segal; Sunita N Misra; Adrian L Rabinowicz; Enrique Carrazana

doi:10.1016/j.yebeh.2023.109248

Concomitant cannabidiol does not impact safety and effectiveness of diazepam nasal spray for seizure clusters: Post hoc analysis of a phase 3 safety study

Epilepsy Behav. 2023 Jul:144:109248. doi: 10.1016/j.yebeh.2023.109248. Epub 2023 May 19.

Authors

Jurriaan M Peters¹, Vinay Puri², Eric Segal³, Sunita N Misra⁴, Adrian L Rabinowicz⁴, Enrique Carrazana⁵

Affiliations

¹ Harvard Medical School and Boston Children's Hospital, 300 Longwood Ave, FE9, Boston, MA 02115, USA. Electronic address: Jurriaan.Peters@childrens.harvard.edu.
² Norton Children's Neuroscience Institute, University of Louisville, 411 E. Chestnut St., Suite 645, Louisville, KY 40202, USA.
³ Hackensack University Medical Center and Northeast Regional Epilepsy Group, 20 Prospect Avenue, Suite 800, Hackensack, NJ 07601, USA.
⁴ Neurelis, Inc., 3430 Carmel Mountain Road, Suite 300, San Diego, CA 92121, USA.
⁵ Neurelis, Inc., 3430 Carmel Mountain Road, Suite 300, San Diego, CA 92121, USA; John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.

PMID: 37210793
DOI: 10.1016/j.yebeh.2023.109248

Abstract

People with epilepsy may experience episodes of frequent seizure activity (seizure clusters, acute repetitive seizures), and benzodiazepines are the cornerstone of rescue treatment. Cannabidiol (CBD) can be used as an adjunctive treatment for epilepsy, and it may interact with other antiseizure drugs, such as benzodiazepines. Here, we examined the safety and effectiveness of intermittent use of diazepam nasal spray in patients with seizure clusters who also received CBD treatment. This analysis included data from patients aged 6 to 65 years enrolled in a phase 3, long-term safety study of diazepam nasal spray. Age- and weight-based dosing of diazepam nasal spray were administered during a 12-month treatment period. Concomitant CBD use was recorded, and treatment-emergent adverse events (TEAEs) were collected. Of 163 treated patients, 119 (73.0%) did not receive CBD, 23 (14.1%) received the US Food and Drug Administration-approved highly purified CBD and 21 (12.9%) received another form of CBD. On average, patients receiving highly purified CBD were younger and more likely to have epileptic encephalopathies, including Dravet syndrome or Lennox-Gastaut syndrome, than patients who received another CBD preparation or no CBD. Rates of TEAEs and serious TEAEs were greater in patients who received any form of CBD (90.9% and 45.5%, respectively) compared with no CBD (79.0% and 26.1%, respectively). However, the lowest rates of TEAEs attributed to diazepam nasal spray were reported in patients who received highly purified CBD (13.0%), and this result was maintained in those who received concomitant clobazam. Use of second doses of diazepam nasal spray, a proxy for effectiveness, was lowest in the highly purified-CBD group (8.2%) compared with the no-CBD (11.6%) and other-CBD groups (20.3%). These results suggest that CBD does not alter the safety and effectiveness of diazepam nasal spray and supports concomitant use in appropriate patients.

Keywords: Acute repetitive seizure; Dravet syndrome; Encephalopathy; Lennox-Gastaut syndrome; Rescue; Rett syndrome.

Publication types

Clinical Trial, Phase III

MeSH terms

Anticonvulsants / adverse effects
Cannabidiol* / adverse effects
Diazepam / adverse effects
Epilepsy* / drug therapy
Humans
Nasal Sprays
Seizures / chemically induced
Seizures / drug therapy
Treatment Outcome

Substances

Anticonvulsants
Cannabidiol
Diazepam
Nasal Sprays