Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy. Issue 10 (25th August 2014)

• Record Type: Journal Article
• Authors: Sperling, Michael R.; Haas, Kevin F.; Krauss, Gregory; Seif Eddeine, Hussam; Henney, Herbert R.; Rabinowicz, Adrian L.; Bream, Gary; Squillacote, David; Carrazana, Enrique J.
• Is Part Of: Epilepsia. Volume 55:Issue 10(2014:Oct.)
• Page Start: 1544
• Page End: 1550
• Publication Date: 2014-08-25
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12755
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12755-abs-0001"> <title>Summary</title> <sec id="epi12755-sec-0001" sec-type="section"> <title>Objective</title> <p>To determine the feasibility of administering a diazepam nasal spray formulation (diazepam‐NS) to adults with epilepsy during a generalized tonic–clonic seizure or in the postictal period following a tonic–clonic or other seizure type, to assess pharmacokinetics and to assess tolerability.</p> </sec> <sec id="epi12755-sec-0002" sec-type="section"> <title>Methods</title> <p>An open‐label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam‐NS approximating 0.2 mg/kg. Plasma diazepam concentrations were measured serially up to 12 h postdose, and maximum observed plasma concentration (C<sub>max</sub>); time to maximum concentration (T<sub>max</sub>); and the area under the plasma concentration–time curve for time zero to last sampling time (AUC<sub>0–12</sub>) were estimated and dose‐normalized. Pharmacodynamic assessments included Kaplan‐Meier analysis to determine the time‐to‐next seizure. Safety and tolerability were assessed.</p> </sec> <sec id="epi12755-sec-0003" sec-type="section"> <title>Results</title> <p>Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic–clonic seizure, seven within 5 min following the last clonic jerk, and 13 in the postictal period ≥5 min after a tonic–clonic or following other seizure‐types. Diazepam median T<sub>max</sub> was 45 min. Dose‐normalized mean C<sub>max</sub> and AUC<sub>0–12</sub> values of diazepam were comparable among patients regardless of the timing of diazepam‐NS administration in relation to seizure. Of those treated, 65% were seizure‐free during the 12‐h observation period and 35% had post‐dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12 h postdose.</p> </sec> <sec id="epi12755-sec-0004" sec-type="section"> <title>Significance</title> <p>Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic–clonic seizures or in the postictal periods following tonic–clonic or other seizure types.</p> </sec> </abstract>