Valtoco nasal spray and diazepam rectal gel: seizure clusters in patients with epilepsy from age 2 years. Libervant buccal film: seizure clusters at ages 2–5 years. Diazepam injection: adjunctive treatment of status epilepticus. Oral Valium: adjunctive treatment of convulsive disorders, not sole therapy.
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.
Adjunctive treatment of convulsive disorders; not sole therapy. Safety and effectiveness below 6 months are not established. Not a rapid seizure-cluster rescue formulation.
U.S. products unless another country is named. Strengths are per unit or stated volume.
Valtoco (intranasal)
Product / formulation
diazepam nasal spray
Labeled ages
2 years and older
Clinical context
FDA-labeled acute treatment of seizure clusters in the listed age range.
Dosing boundary
Age- and weight-band dose: 0.5 mg/kg at ages 2–5, 0.3 mg/kg at ages 6–11, and 0.2 mg/kg at age 12 and older. One 5- or 10-mg device for those doses; 15 or 20 mg requires one device in each nostril.
Repeat dose / frequency
If prescribed and needed, at least 4 hours after the first dose; use a new blister pack. Do not repeat for concerning breathing, need for breathing assistance, or extreme drowsiness. No more than 2 doses per episode; no more than 1 episode every 5 days and 5 episodes per month.
Product pharmacokinetics
Tmax: 1.5 hours in healthy adults. Bioavailability: 97% absolute bioavailability relative to IV diazepam in healthy adults. Terminal half-life: Diazepam mean 49.2 hours after a 10-mg nasal dose. Active nordazepam can persist much longer; the Valtoco label cites diazepam metabolism but does not give a Valtoco-specific nordazepam half-life.
Evidence basis
No product-specific randomized efficacy endpoint. FDA-labeled effectiveness is based on relative bioavailability to diazepam rectal gel, whose controlled trials assessed seizure frequency, global assessment, time to next seizure, and seizure-free status during 12- or 24-hour observation. Bridged rectal-gel evidence: Study 1 seizure-free during observation, 62% versus 20% (absolute difference +42 percentage points); Study 2, 55% versus 34% (+21 points). These are not direct Valtoco effect estimates.
FDA-labeled acute treatment of seizure clusters in the listed age range.
Dosing boundary
Age- and weight-based rectal dose: 0.5 mg/kg at ages 2–5, 0.3 mg/kg at ages 6–11, and 0.2 mg/kg at age 12 and older, rounded upward to the available 2.5-mg dose increments shown in the label.
Repeat dose / frequency
A prescriber may order a second dose 4–12 hours after the first dose. No more than 1 episode every 5 days and 5 episodes per month; follow the prescribed number of doses for the episode.
Product pharmacokinetics
Tmax: 1.5 hours in healthy adults. Bioavailability: 90% absolute bioavailability relative to injectable diazepam in healthy adults. Terminal half-life: Diazepam about 46 hours and active desmethyldiazepam about 71 hours after a 15-mg rectal dose.
Evidence basis
Study 1: seizure frequency during observation plus caregiver global assessment incorporating seizure frequency, severity, and nature. Study 2: seizure frequency over 12 hours; time to next seizure and seizure-free status were additional outcomes. Study 1 median 0 versus 0.3 seizures/hour and seizure-free status 62% versus 20% (+42 points). Study 2 median 0 versus 2.0 seizures/12 hours and seizure-free status 55% versus 34% (+21 points).
FDA-labeled acute treatment of seizure clusters in the listed age range.
Dosing boundary
Weight-band whole film placed on the inside of the cheek: 5 mg at 6–10 kg, 7.5 mg at 11–15 kg, 10 mg at 16–20 kg, 12.5 mg at 21–25 kg, and 15 mg at 26–30 kg. Do not split, chew, swallow, or administer with liquids.
Repeat dose / frequency
If prescribed and needed, at least 4 hours after the first dose. Do not repeat for concerning breathing, need for assisted breathing/intubation, or more sleepiness than normal. No more than 2 doses per episode; no more than 1 episode every 5 days and 5 episodes per month.
Product pharmacokinetics
Tmax: Approximately 1 hour in fasting healthy adults. Bioavailability: The current U.S. label does not state an absolute percentage. Approval relied in part on adult relative-bioavailability studies comparing Libervant with diazepam rectal gel. Terminal half-life: Diazepam about 86 hours and active desmethyldiazepam about 147 hours in Libervant studies. In children age 2–5, literature-based IV diazepam half-life is about 15–21 hours; the label cautions that age and study context matter.
Evidence basis
No product-specific randomized efficacy endpoint. Effectiveness was bridged from controlled diazepam rectal-gel trials using seizure frequency, global assessment, time to next seizure, and seizure-free status, together with adult/pediatric pharmacokinetic and open-label safety data. Bridged rectal-gel evidence: seizure-free status 62% versus 20% (+42 points) in Study 1 and 55% versus 34% (+21 points) in Study 2. These are not direct Libervant effect estimates.
Adjunctive oral treatment in selected convulsive disorders and other labeled non-epilepsy indications. It is not an FDA-approved outpatient rapid seizure-cluster rescue product.
Dosing boundary
Use the exact oral product label and prescribed schedule; oral concentrate and solution concentrations are not interchangeable by volume.
Product pharmacokinetics
Oral diazepam is more than 90% absorbed; terminal elimination may be up to about 48 hours in adults and varies strongly with age and liver function.
Evidence basis
Legacy diazepam evidence and product labeling; do not extrapolate nasal, rectal, or buccal rescue dosing to oral products.
Adjunctive treatment of status epilepticus in a monitored setting, as described in the injection label.
Dosing boundary
Use the current injection label and institutional emergency protocol with airway, respiratory, and cardiovascular monitoring.
Product pharmacokinetics
IV bioavailability is 100%. Diazepam terminal half-life is strongly age-dependent (about 15 hours at age 18 in cited IV data, longer with age); active metabolites can persist much longer.
Evidence basis
Established emergency use supported by product labeling and U.S. status-epilepticus guidance.
Nasal: 0.2 mg/kg, using the labeled weight-band dose (5–20 mg). IV status: 5–10 mg slowly, at least 1 minute per 5 mg; may repeat every 10–15 minutes to 30 mg with respiratory support available.
Pediatric
Nasal/rectal: ages 2–5, 0.5 mg/kg; 6–11, 0.3 mg/kg; ≥12, 0.2 mg/kg. Use the specific product’s weight table; nasal and rectal dose bands differ. Pediatric IV dosing is product/protocol specific.
Titration / repeat dosing
Rescue, not daily titration. Valtoco and Libervant: prescribed second dose ≥4 hours later; rectal gel: prescribed second dose 4–12 hours later. Maximum 2 doses/episode for Valtoco and Libervant; all three diazepam cluster products are limited to ≤1 episode/5 days and ≤5/month. Withhold repeat dosing for concerning breathing or excessive sedation and obtain emergency help.
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
Valtoco: diazepam hypersensitivity; acute narrow-angle glaucoma. Consult the separate injection label for route-specific restrictions.
Serious precautions & monitoring
Use an individualized rescue plan. IV treatment requires airway/respiratory monitoring; recurrent seizures require further status management.
Diazepam exposure late in pregnancy can cause neonatal sedation or withdrawal. Published benzodiazepine observational data do not show a clear association with major birth defects; animal developmental toxicity is reported.
Pregnancy / postpartum monitoring
After exposure near delivery, monitor the newborn for respiratory depression, hypotonia, feeding difficulty and withdrawal.
Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.
Direct pivotal trialPharmacokinetic bridgeGuideline-supported off-label useObservational evidence
Trial summary
Study design / duration
Rectal study: randomized, double-blind, caregiver-administered treatment; 91 treated patients, children and adults, with age-dependent 12/24-hour observation. Nasal safety study: repeated outpatient treatment, open label.
Primary endpoint
Product-specific. Diazepam rectal-gel trials assessed seizure frequency, caregiver global assessment, time to next seizure, and seizure-free status over 12–24 hours. Valtoco and Libervant did not use a direct randomized efficacy endpoint; their effectiveness was pharmacokinetically bridged to rectal gel.
Results
Rectal-gel Study 1: seizure-free during observation 62% versus 20% (+42 percentage points). Study 2: 55% versus 34% (+21 points). These bridged results are not direct Valtoco or Libervant effect estimates.
Confidence intervals
The current U.S. labels report p-values but not confidence intervals for the rectal-gel endpoint differences.
Discontinuations
Controlled rectal-gel trials: 2% with diazepam rectal gel and 2% with placebo discontinued for adverse events. No product-specific randomized efficacy-trial discontinuation rate exists for Valtoco or Libervant.
Exposure duration
Rectal-gel efficacy observation: 12 hours in children and 24 hours in adults in Study 1; 12 hours in Study 2. Valtoco safety exposure included 255 patients (143 for at least 1 year); Libervant safety exposure included 197 patients (107 for at least 6 months; 48 for at least 1 year).
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
Route-specific: nasal Valtoco approximately 97% and rectal gel approximately 90% absolute bioavailability relative to IV. The Libervant label does not state an absolute percentage; its approval used adult relative-bioavailability comparisons with rectal gel. Oral diazepam is >90% absorbed; absorption is not the same measurement as absolute bioavailability.
Elimination half-life
Route-, study- and population-dependent: mean diazepam half-life 49.2 hours after 10 mg intranasal Valtoco, about 46 hours after 15 mg rectal gel, and about 86 hours in Libervant studies; oral Valium terminal elimination is up to 48 hours. IV literature values cited in these labels are about 15–21 hours in children and about 15 hours at age 18, increasing markedly with age. These cross-study differences do not prove that formulation alone changes elimination and do not define rescue onset or duration.
Volume of distribution
Approximately 0.8–1.0 L/kg at steady state (Valtoco label).
Active metabolite(s)
Yes: N-desmethyldiazepam (nordazepam), temazepam and oxazepam.
Active-metabolite half-life
Active desmethyldiazepam (nordazepam): about 71 hours after rectal gel and about 147 hours in Libervant studies; other diazepam sources report up to 100 hours. Temazepam: 3.5–18.4 hours (mean 8.8); oxazepam: 5.7–10.9 hours (mean 8.2), from their own product-label studies after direct dosing. Values are route-, study-, age-, and population-specific.
Protein binding
~98%
Metabolism / elimination
CYP2C19 / CYP3A4
Age, liver disease and repeated dosing may prolong exposure. Long terminal half-life does not establish the duration of rapid rescue protection.
Yes: oral, injectable and rectal products; verify nasal-product availability separately.
Related drugs
1,4-benzodiazepine family: clonazepam, lorazepam, midazolam; clobazam is a 1,5-benzodiazepine.
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.
Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 6/2025. This is a draft reference; final review is pending.
