Oromucosal midazolam: a review of its use in pediatric patients with prolonged acute convulsive seizures.
Oromucosal midazolam (Buccolam™) is a benzodiazepine approved for the treatment of pediatric patients with acute, prolonged, convulsive seizures. This article reviews the pharmacologic properties of oromucosal midazolam and its clinical efficacy and tolerability for the treatment of prolonged acute convulsive seizures in pediatric patients aged 3 months to <18 years. Midazolam exerts its action by enhancing the effects of γ-aminobutyric acid (GABA) on GABA(A) receptors, resulting in neural inhibition. Oromucosal midazolam has a rapid onset (<10 minutes; due to rapid absorption across the buccal membrane and high lipophilicity) and short duration of effect (categorized by the short elimination half-life of midazolam and its active metabolite). The oromucosal administration of the drug avoids first-pass hepatic metabolism; as a result, it has a higher bioavailability than oral midazolam. Oromucosal midazolam is at least as effective at seizure cessation as rectal or intravenous diazepam and appears as well tolerated as these diazepam formulations in pediatric patients with acute convulsive seizures (additionally, midazolam has been available for use for decades in various formulations, and is historically well tolerated). Moreover, oromucosal midazolam was associated with a similar or shorter time to response than rectal diazepam. While the time to response was longer with oromucosal midazolam than with intravenous diazepam, the latter took significantly longer to apply than the former, leading to a significantly shorter overall controlling time with oromucosal midazolam. Respiratory depression occurred at a similar rate in recipients of oromucosal midazolam to that observed in recipients of rectal diazepam. Overall, oromucosal midazolam is at least as effective as rectal diazepam and as effective as intravenous diazepam in the treatment of children with prolonged acute convulsive seizures, and is generally well tolerated in this population. It has several advantages over rectal diazepam, the previous gold standard of treatment, such as having a more socially acceptable administration route and having a likely more predictable absorption profile. Oromucosal midazolam is a promising first-line treatment option for children with prolonged acute convulsive seizures, in particular where intravenous access is precluded.
Adis, Auckland, New Zealand.
Karly P
KP
Garnock-Jones
D000278:Administration, Buccal; D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D006801:Humans; D007223:Infant; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D008874:Midazolam