What is the recommended dose and administration of midazolam (benzodiazepine) nasal spray for acute seizure management?

Midazolam Nasal Spray for Acute Seizure Management

The recommended dose of midazolam nasal spray for acute seizure management is 5 mg for adults and adolescents 12 years and older, with the option for a second dose if seizures do not terminate within 10 minutes or recur within 10 minutes to 6 hours after administration. 1, 2

Dosing Recommendations by Age

Adults and Adolescents (≥12 years)

• Standard dose: 5 mg administered as a single nasal spray 1, 3
• A second 5 mg dose may be given if seizures do not terminate within 10 minutes or recur within 10 minutes to 6 hours 2
• No dosage adjustment is needed based on age (≥12 years), sex, race, body weight, or body mass index 4

Pediatric Patients (6 months to 12 years)

• For children 6 months to 5 years: 0.2 mg/kg intranasally 5
• For children 6 to 12 years: dosing should be adjusted based on weight, typically 0.2 mg/kg intranasally 5, 6

Special Populations

• Elderly patients (≥60 years) or debilitated patients may require dose reduction due to increased risk of respiratory depression 1
• Patients with hepatic impairment may require dose reduction due to decreased clearance 7, 1
• Patients on concomitant CNS depressants may require dose reduction 8, 1

Administration Technique

• Administer as a single spray into one nostril while the patient is in a recumbent position 3
• No need for priming the device before use 3
• Can be administered by non-healthcare providers in outpatient settings 4, 2

Clinical Efficacy

• Treatment success (defined as seizure termination within 10 minutes and no recurrence within 6 hours) is achieved in approximately 55% of seizure episodes with a single 5 mg dose 2
• With a second dose, treatment success increases to approximately 80% 2
• Intranasal midazolam has shown comparable efficacy to intramuscular and buccal routes for acute seizure management 6

Pharmacokinetics and Onset of Action

• Rapid absorption with peak plasma concentrations (tmax) reached in 9.0-21.5 minutes 4
• Onset of CNS effects within 10 minutes after administration 4
• Duration of action: return to baseline alertness by approximately 4 hours post-dose 4
• Elimination half-life: 3.6-8.1 hours 4

Safety Considerations

• Monitor for respiratory depression, especially in patients with underlying respiratory disease or when combined with other CNS depressants 7, 8
• Most common adverse effects include nasal discomfort (12.4%) and somnolence (9.3%) 2
• Serious respiratory depression occurs in approximately 1% of cases 5
• Avoid co-administration with moderate or strong CYP3A4 inhibitors as they may prolong midazolam effects 4
• Use with caution when co-administered with mild CYP3A4 inhibitors 4

Practical Considerations

• Intranasal administration provides a non-invasive alternative to intravenous or intramuscular routes, particularly valuable in outpatient settings 4, 6
• High satisfaction rate among caregivers compared to other routes of administration 6
• No evidence of tolerance development with repeated intermittent use over extended periods 2
• No reports of drug abuse or dependence with midazolam nasal spray in clinical studies 2

Algorithm for Acute Seizure Management with Midazolam Nasal Spray

1. Identify seizure requiring intervention (typically lasting >5 minutes or cluster of seizures) 6
2. Administer 5 mg midazolam nasal spray (adults and adolescents ≥12 years) or weight-based dose for younger children 1, 5
3. Position patient on their side to prevent aspiration 8
4. Monitor respiratory status and oxygen saturation if possible 8
5. If seizure does not terminate within 10 minutes or recurs within 10 minutes to 6 hours, administer a second dose 2
6. If seizures continue after second dose, seek emergency medical care 9