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

Abstract

SUMMARYRectal 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 seizureexacerbations 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.

Intranasal Delivery of Two Benzodiazepines, Midazolam and Diazepam, by a Microemulsion System

“…However, diazepam via intravenous and rectal routes have several drawbacks [5][6][7][8]: 1) The establishment of an intravenous access is not practical in an emergency situation when the patient is not in a hospital. A highly qualified, trained medical person is required for this procedure; 2) The use of rectal diazepam results in variable plasma levels and fails to terminate 30% of seizures [9].…”

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

“…Clinical studies on the use of intranasal BDZs for the acute management of seizures are available for MDZ [13][14][15][16][17][18][19][20][21][22] and LZP [23,24] suggesting that, in both cases, the intranasal delivery is a potentially efficient alternative root of administration (Table 3) and ad hoc technologies are currently under investigation. In particular, there are two intranasal DZP formulations currently under development by Neurelis (10 mg) and Acorda Therapeutics (20 mg) and a MDZ intranasal formulation by Upsher-Smith Laboratories (2.5 mg, 5 mg, 7.5 mg) [10].…”

“…A number of trials compared intranasal MDZ with either rectal DZP or intravenous DZP [13][14][15][16][17][18][19][20][21][22] (Table 3). Available data suggests that intranasal MDZ is effective, safe and more efficient that rectal DZP in controlling seizure activity [7] (Table 3).…”

Benzo versus Benzo: And the Winner Is…

“…A number of different benzodiazepines as well as different routes of administration have been pitted against each other. Studies have compared rectal diazepam versus intranasal and buccal midazolam, intravenous lorazepam versus intravenous diazepam, and buccal midazolam versus intravenous diazepam, to name a few (1)(2)(3)(4). The current study takes a slightly different tack, as it compares two different routes of administration of the same benzodiazepine, namely, lorazepam.…”