FDA Approves Diazepam Nasal Spray for Children Aged 2 to 5 With Seizure Clusters
The US Food and Drug Administration (FDA) has expanded approval of immediate-use VALTOCO (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity—also known as seizure clusters or acute repetitive seizures—in pediatric patients over 2 years of age. The drug was previously approved in 2020 for use in patients over 6 years old.
"For children who have episodes of frequent seizures, the current standard of care requiring rectal administration of medication to stop a seizure can be a significant challenge for caregivers and children alike," said Jurriaan M Peters, MD, PhD, director, Localization Laboratory, Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, and associate professor in neurology at Harvard Medical School.
Diazepam nasal spray utilizes an intravail transmucosal absorption enhancement technology that facilitates noninvasive drug delivery. The drug's orphan drug designation remains in place due to its clinical superiority over rectal diazepam, which was recognized by the FDA in 2020.
Approval was supported by phase 1/2a clinical study data demonstrating safety and pharmacokinetic efficacy in children aged 2 to 5, with common adverse reactions including somnolence, headache, and nasal discomfort.
Boxed Warnings and Contraindications
- Diazepam nasal spray carries FDA-mandated boxed warnings for:
- Risks associated with concomitant use of benzodiazepines and opioids (ie, profound sedation, respiratory depression, coma, death);
- Potential for abuse, misuse, and addiction that can lead to overdose or death; and
- Risk of dependence and potentially life-threatening withdrawal reactions if used more frequently than recommended.
Diazepam nasal spray is contraindicated in patients with the following conditions:
- Hypersensitivity to diazepam
- Acute narrow-angle glaucoma
Clinical Considerations for Neurologists
Clinicians should be vigilant regarding central nervous system (CNS) depression with the use of diazepam nasal spray both when administered alone and when co-administered with other CNS depressants or alcohol. As with other antiepileptic drugs, diazepam nasal spray may increase the risk of suicidal ideation and behavior as well as increase the risk of intraocular pressure in patients with glaucoma. Treating patients with diazepam nasal spray who are late in their pregnancy can result in sedation and withdrawal symptoms in the neonate.
Diazepam nasal spray remains a Schedule IV controlled substance and is not approved for neonates due to the risk of serious adverse reactions related to its benzyl alcohol content.
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