What is the recommended dose of midazolam (Benzodiazepine) nasal spray for an ongoing seizure based on age and weight?

Midazolam Nasal Spray Dosing for Ongoing Seizures

For patients 12 years and older experiencing an ongoing seizure, administer midazolam nasal spray 5 mg as a single dose, which can be repeated once if the seizure does not terminate within 10 minutes or recurs between 10 minutes and 6 hours after the first dose. 1, 2

Age and Weight-Based Dosing Algorithm

Pediatric Patients (Children and Adolescents ≥12 years)

• Standard dose: 5 mg intranasal (not weight-based for nasal spray formulation) 1, 2
• This fixed dose has been validated in clinical trials for patients 12 years and older regardless of weight 3, 4
• Maximum of 2 doses per seizure cluster episode 2

Important Distinction: Nasal Spray vs Other Intranasal Formulations

The commercially available midazolam nasal spray uses a fixed 5 mg dose for patients ≥12 years, which differs from weight-based intranasal dosing recommendations (0.2 mg/kg, maximum 6 mg) that apply to compounded or off-label intranasal preparations used in younger children. 1

Dosing for Younger Children (<12 years)

For children under 12 years where the commercial nasal spray is not indicated, alternative routes should be used:

• Intranasal (compounded): 0.2 mg/kg (maximum 6 mg per dose) 1
• Intramuscular: 0.2 mg/kg (maximum 6 mg per dose) 5, 1
• Intravenous: 0.05-0.10 mg/kg over 2-3 minutes (maximum single dose 5 mg) 5, 1
• May repeat every 10-15 minutes if seizures persist 5, 1

Efficacy and Timing Expectations

Treatment success occurs in 55% of seizure cluster episodes after a single 5 mg dose, increasing to 80.2% when a second dose is administered. 2 The medication demonstrates:

• Rapid absorption with peak concentration at 9-21.5 minutes 6
• Onset of sedation within 10 minutes 6
• Seizure termination typically within 3-4 minutes in responders 7

Critical Safety Monitoring

Respiratory Depression Risk

• Monitor oxygen saturation continuously and be prepared to provide respiratory support regardless of administration route 5, 1
• Apnea can occur up to 30 minutes after administration, particularly when combined with other sedatives 5
• Have flumazenil available for reversal, though note it will also reverse anticonvulsant effects and may precipitate seizures 5, 1

Common Adverse Effects

The most frequently reported side effects within 2 days of administration are:

• Nasal discomfort (12.4% of patients) 2
• Somnolence (9.3% of patients) 2
• No treatment-related respiratory depression was observed in extended safety trials 2

Escalation for Refractory Seizures

If seizures persist despite two doses of nasal spray:

• IV loading dose: 0.15-0.20 mg/kg 5, 1
• Continuous infusion: Start at 1 μg/kg/min (0.06 mg/kg/hr), titrate by 1 μg/kg/min increments every 15 minutes 5, 1
• Maximum infusion rate: 5 μg/kg/min (0.3 mg/kg/hr) 5, 1

Common Pitfalls to Avoid

• Do not delay treatment attempting IV access when nasal spray is immediately available 1
• The commercial nasal spray formulation is NOT weight-based; do not attempt to calculate doses based on patient weight for the 5 mg spray device 3, 2
• Do not use lower doses for seizure control—they are ineffective 1
• Watch for paradoxical agitation, especially in younger children (6% incidence) 8
• Avoid rapid IV administration if that route is used, as it increases risk of oversedation and hypotension 1

Drug Interactions Requiring Dose Adjustment

• Avoid coadministration with moderate or strong CYP3A4 inhibitors (may prolong effects due to decreased clearance) 6
• Use caution with mild CYP3A4 inhibitors 6
• CYP3A4-inducing antiepileptic drugs do not require dose adjustment for nasal spray 6