Nayzilam nasal spray: seizure clusters in patients with epilepsy from age 12 years. Seizalam intramuscular injection and the specified 10 mg/0.7 mL intramuscular autoinjector: status epilepticus in adults. Other midazolam formulations have separate labels.
Role
Rescue / acute treatment
Class
1,4-benzodiazepine
Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.
U.S. products unless another country is named. Strengths are per unit or stated volume.
Nayzilam (intranasal)
Product / formulation
midazolam nasal spray
Labeled ages
12 years and older
Clinical context
FDA-labeled acute treatment of seizure clusters in the listed age range.
Dosing boundary
One 5-mg single-use device sprayed into one nostril; a prescribed second 5-mg dose uses a new device in the opposite nostril.
Repeat dose / frequency
If prescribed and the patient has not responded, after 10 minutes in the opposite nostril. Do not repeat for breathing trouble or uncharacteristic excessive sedation. No more than 2 doses per episode; no more than 1 episode every 3 days and 5 episodes per month.
Product pharmacokinetics
Tmax: Median 17.3 minutes (range 7.8–28.2) in healthy adults. Bioavailability: Approximately 44% absolute bioavailability in healthy adults. Terminal half-life: Midazolam median 2.1–6.2 hours; active 1-hydroxymidazolam 2.7–7.2 hours in Nayzilam studies.
Evidence basis
Treatment success: seizure termination within 10 minutes after the initial blinded dose and no seizure recurrence from 10 minutes through 6 hours. U.S. label: 53.7% with Nayzilam versus 34.3% with placebo; absolute difference +19.4 percentage points (p=0.011). Termination within 10 minutes: 80.6% versus 70.1%; no recurrence from 10 minutes through 6 hours: 58.2% versus 37.3%.
Nayzilam 5 mg in one nostril. Seizalam: 10 mg IM in adults, with continuous respiratory/cardiac monitoring.
Pediatric
Nayzilam from age 12 years: the labeled initial dose is 5 mg. No younger-pediatric or other-route seizure regimen is listed here.
Titration / repeat dosing
Nasal: if needed, 5 mg in opposite nostril after 10 minutes; maximum 2 doses, ≤1 episode/3 days and ≤5/month. Do not repeat with breathing difficulty or uncharacteristic excessive sedation.
Boxed: opioid-associated respiratory depression, abuse/misuse/addiction, and dependence/withdrawal. No reliable single incidence estimate; risk depends on exposure and co-sedatives. Avoid abrupt withdrawal after repeated use.
Contraindications
Nayzilam: midazolam hypersensitivity and acute narrow-angle glaucoma. Review the separate IM product label.
Midazolam exposure late in pregnancy or during labor can cause neonatal sedation, respiratory depression or withdrawal. Published benzodiazepine observational data do not show a clear major-malformation association; animal developmental neurotoxicity is reported.
Pregnancy / postpartum monitoring
Monitor exposed newborns for sedation, feeding difficulty and withdrawal.
Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.
Direct pivotal trialGuideline-supported off-label use
Trial summary
Study design / duration
Nasal: randomized, double-blind, placebo-controlled outpatient cluster trial, 201 treated after test-dose screening; success = termination within 10 minutes and no recurrence through 6 hours. RAMPART: double-blind Phase 3 prehospital noninferiority trial, n=893.
Primary endpoint
Nayzilam treatment success: seizure termination within 10 minutes after the initial blinded dose and no recurrence from 10 minutes through 6 hours. RAMPART used seizure absence without rescue therapy at emergency-department arrival.
Results
Nayzilam: 53.7% versus 34.3% placebo, absolute difference +19.4 percentage points (p=0.011). RAMPART: 73.4% IM midazolam versus 63.4% IV lorazepam, absolute difference +10.0 points in the prehospital route strategy.
Confidence intervals
Nayzilam treatment-success 95% CI: 45.3%–62.2% with active treatment and 23.0%–45.7% with placebo; the label does not give a CI for the absolute difference. Use the RAMPART publication/FDA review for its prespecified noninferiority interval.
Discontinuations
The Nayzilam label does not report a Comparative Phase adverse-event discontinuation rate. Its open-label test-dose phase screened tolerability before the randomized phase, limiting generalizability.
Exposure duration
Nayzilam randomized phase: one outpatient seizure cluster, 6-hour primary window, time to next seizure through 24 hours. RAMPART: a single prehospital status-epilepticus episode through emergency-department arrival.
A 1,4-benzodiazepine that enhances GABA-dependent gating of benzodiazepine-sensitive GABA-A chloride channels at the classical α/γ subunit-interface site. This is distinct from the GABA-binding site and from GABA-B receptors.
The classical teaching is increased opening/burst frequency for benzodiazepines versus longer openings for barbiturates. Single-channel behavior depends on preparation and conditions, so this is a useful distinction rather than an absolute kinetic rule.
Route, onset, duration, active metabolites and clearance distinguish these drugs clinically, but those pharmacokinetic differences are not separate receptor mechanisms.
Adult values unless specified. Vd/F denotes apparent oral distribution volume.
Pharmacokinetics
Bioavailability
Nayzilam nasal: approximately 44% absolute bioavailability. IV: 100%; IM absorption is generally high (>90%).
Elimination half-life
Intranasal Nayzilam: median elimination half-life 2.1–6.2 hours. Parenteral values vary with clinical setting and patient factors; do not infer that route alone determines terminal half-life.
Volume of distribution
Nayzilam label: estimated total volume 226.5 L. This is a route/study-specific estimate, not a universal weight-based value.
Active metabolite(s)
Yes: 1-hydroxymidazolam (α-hydroxymidazolam); its glucuronide can accumulate in renal failure and contribute to prolonged effects.
Active-metabolite half-life
1-hydroxymidazolam: 2.7–7.2 hours in Nayzilam studies. The glucuronide half-life exceeded 25 hours in an acute-renal-failure ICU study; do not apply that as a normal-population value.
Protein binding
~97%
Metabolism / elimination
CYP3A4/5
Critical illness, renal failure, hepatic impairment and CYP3A inhibitors can substantially prolong sedation.
1,4-benzodiazepine; route-specific rescue products are not interchangeable.
Sources & review status
Representative sources are selected product labels, not an exhaustive list of generic manufacturers. Consult the exact product and formulation prescribed. Brand-name package inserts are linked separately.
The historical Versed record covers the injectable sedation/anesthesia product; it does not establish a seizure-rescue indication or replace current product labeling.
Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 1/2023. This is a draft reference; final review is pending.
