Evidence map›Paper›PMID 35377464›Full record

ArticleEpilepsia2022

Lack of clinically relevant differences in safety and pharmacokinetics after second-dose administration of intranasal diazepam within 4 h for acute treatment of seizure clusters: A population analysis.

Gregory D Cascino, Daniel Tarquinio, James W Wheless, Robert Edward Hogan, Michael R Sperling, Jay Desai, Blanca Vazquez, Emil Samara, Sunita N Misra, Enrique Carrazana and 2 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 10 institutions in 2 countries.

Gregory D CascinoMayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-5380-2977
Daniel TarquinioCenter for Rare Neurological Diseases, Atlanta, Georgia, USA.
James W WhelessLe Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, Tennessee, USA.ORCID 0000-0002-4735-3431
Robert Edward HoganWashington University in St Louis, St Louis, Missouri, USA.ORCID 0000-0003-2272-5005
Michael R SperlingThomas Jefferson University, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-0708-6006
Jay DesaiChildren's Hospital of Los Angeles, California, USA.
Blanca VazquezComprehensive Epilepsy Center, New York University, New York, New York, USA.
Emil SamaraPharmaPolaris International, Washington, District of Columbia, USA.
Sunita N MisraNeurelis, San Diego, California, USA.ORCID 0000-0002-7624-8825
Enrique CarrazanaNeurelis, San Diego, California, USA.ORCID 0000-0001-8788-0722
Adrian L RabinowiczNeurelis, San Diego, California, USA.ORCID 0000-0003-1299-0606
DIAZ.001.05 Study Group
Neurelis (United States) · USChildren's Hospital of Los Angeles · USEpilepsy Action · GBMayo Clinic · USNational Center for Infectious Diseases · USPolaris (United States) · USThomas Jefferson University · USUniversity of Hawaiʻi at Mānoa · USUniversity of Tennessee Health Science Center · USWashington University in St. Louis · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveCurrent diazepam nasal spray labeling requires waiting 4 h before administering a second dose. The objective of the current analyses was to examine safety and pharmacokinetic profiles of second doses of diazepam nasal spray given 0-4 h after the first dose.

methodsTwo datasets were analyzed. The first, a long-term, repeat-dose safety study of diazepam nasal spray, compared rates of treatment-emergent adverse events (TEAEs), serious TEAEs, and treatment-related TEAEs for patients receiving ≥1 second dose ≤4 h versus all second doses >4 h after the first. The second was a population pharmacokinetic analysis using data from three phase 1 studies to model drug exposure when a second dose of diazepam nasal spray was administered across multiple time points (1 min-4 h) following the first dose.

resultsIn the repeat-dose safety study, a second dose of diazepam nasal spray was administered ≤24 h after the first to treat 485 seizure clusters in 79 patients. Rates of TEAEs were similar between patients receiving ≥1 second dose in ≤4 h (89.5%, n = 38) compared with >4-24 h only (80.5%, n = 41). The most common treatment-related TEAEs were associated with nasal discomfort, which was mild or moderate and transient. There were no reports of respiratory or cardiac depression. The pharmacokinetic simulations of second doses predicted comparable elevations of plasma diazepam concentrations with administrations across a range of intervals after the first dose (1 min-4 h). SIGNIFICANCE: These data indicate that the safety and pharmacokinetic profiles of a second dose of diazepam nasal spray administered within 4 h of the first dose are consistent with those associated with current labeling. This is potentially important for patients with seizure clusters who have a recurrent seizure within 4 h of first treatment and might benefit from immediate retreatment to reduce the risk of progression to status epilepticus.

Indexed as

DiazepamEpilepsy, GeneralizedAdministration, IntranasalAnticonvulsantsHumansNasal SpraysSeizuresAnticonvulsantsDiazepamNasal Spraysacute repetitive seizurebenzodiazepinenasal sprayseizure emergency

Identifiers

PMID35377464
PMCPMC9543781
OpenAlexW4224095667

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.