A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations

Rectal diazepam is established as a standard rescue or emergency treatment for seizure or status epilepticus; however, the rectal route of administration has not been universally accepted. To determine if an alternative route of administration of a benzodiazepine was equally effective, we compared a novel midazolam HCl concentrated nasal spray (MDZ‐n) with diazepam rectal solution (DZP‐r) in the treatment of prolonged seizures in a residential epilepsy center. In 21 adult patients with medically refractory epilepsy, 124 seizure‐exacerbations were treated by their caregivers, alternatively with 10 mg DZP‐r and 10 mg concentrated MDZ‐n, two or three treatments with each medication for each patient. No difference was demonstrated in efficacy or time to effect between the two drugs. Common treatment emerging adverse effects were drowsiness for both drugs in more than 50% of the administrations, and short‐lasting local irritation after 29% of MDZ‐n. No severe adverse events occurred. The nasal spray was preferred to the rectal solution by 16 of 21 caregivers and patients conjointly. MDZ‐n was equal to DZP‐r with respect to efficacy and side effects in the suppression of seizure exacerbations. The majority of patients and caregivers preferred the nasal spray over the rectal formulation.

[1]  E. Molyneux,et al.  Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: an open randomised trial , 2006, The Lancet.

[2]  M. Bhattacharyya,et al.  Intranasal midazolam vs rectal diazepam in acute childhood seizures. , 2006, Pediatric neurology.

[3]  Jacqueline Collier,et al.  Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial , 2005, The Lancet.

[4]  S. Carley,et al.  Intranasal midazolam in patients with fits , 2005, Emergency Medicine Journal.

[5]  R. Body,et al.  Buccal midazolam as an alternative to rectal diazepam for prolonged seizures in childhood and adolescence , 2005, Emergency Medicine Journal.

[6]  M. Gemma Management of status epilepticus , 1994, Intensive Care Medicine.

[7]  S. Carley,et al.  Best evidence topic report. Intranasal midazolam in patients with fits. , 2005, Emergency medicine journal : EMJ.

[8]  R. Body,et al.  Best evidence topic report. Buccal midazolam as an alternative to rectal diazepam for prolonged seizures in childhood and adolescence. , 2005, Emergency medicine journal : EMJ.

[9]  John W. Miller,et al.  Treatment of out-of-hospital status epilepticus with diazepam rectal gel , 2003, Seizure.

[10]  J. Kapur Prehospital Treatment of Status Epilepticus with Benzodiazepines is Effective and Safe , 2002, Epilepsy currents.

[11]  D. Jonker,et al.  Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers. , 2002, British journal of clinical pharmacology.

[12]  P. Zorlu,et al.  Effects of Intranasal Midazolam and Rectal Diazepam on Acute Convulsions in Children: Prospective Randomized Study , 2002, Journal of child neurology.

[13]  M R Segal,et al.  A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. , 2001, The New England journal of medicine.

[14]  C. Okuyaz,et al.  Nasal Midazolam Effects on Childhood Acute Seizures , 2000, Journal of child neurology.

[15]  M. Ibitoye,et al.  Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy? , 2000, Seizure.

[16]  Rod C Scott,et al.  Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial , 1999, The Lancet.

[17]  H. Striebel,et al.  Midazolam pharmacokinetics following intravenous and buccal administration. , 1998, British journal of clinical pharmacology.

[18]  G. Geldner,et al.  Comparison between three transmucosal routes of administration of midazolam in children , 1997, Paediatric anaesthesia.

[19]  R. Goldberg,et al.  Intranasal midazolam in patients with status epilepticus. , 1997, Annals of Emergency Medicine.

[20]  R. Janknegt,et al.  Absorption of clonazepam after intranasal and buccal administration. , 1995, British journal of clinical pharmacology.

[21]  S. Shorvon Status Epilepticus: Its Clinical Features and Treatment in Children and Adults , 1994 .

[22]  R. Dieckmann Rectal diazepam for prehospital pediatric status epilepticus. , 1994, Annals of emergency medicine.