Rescue-treatment comparison

Four outpatient seizure-cluster products. Follow the patient’s prescribed seizure action plan; products, doses, and repeat-dose intervals are not interchangeable. For an emergency, call emergency services.

Plasma peak time is not time to seizure control. Separate studies do not establish that one product is more effective than another.

Clinical detail	Valtoco	Nayzilam	Diastat / diazepam rectal gel	Libervant
Labeled ages	2 years and older	12 years and older	2 years and older	2 through 5 years
Dose method	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. See age/weight table ↓	One 5-mg single-use device sprayed into one nostril; a prescribed second 5-mg dose uses a new device in the opposite nostril.	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. See age/weight table ↓	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. See age/weight table ↓
Tmax (plasma peak; not onset)	1.5 hours in healthy adults	Median 17.3 minutes (range 7.8–28.2) in healthy adults	1.5 hours in healthy adults	Approximately 1 hour in fasting healthy adults
Second-dose timing	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.	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.	A prescriber may order a second dose 4–12 hours after the first dose.	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.
Maximum frequency	No more than 2 doses per episode; no more than 1 episode every 5 days and 5 episodes per month.	No more than 2 doses per episode; no more than 1 episode every 3 days and 5 episodes per month.	No more than 1 episode every 5 days and 5 episodes per month; follow the prescribed number of doses for the episode.	No more than 2 doses per episode; no more than 1 episode every 5 days and 5 episodes per month.
Bioavailability	97% absolute bioavailability relative to IV diazepam in healthy adults.	Approximately 44% absolute bioavailability in healthy adults.	90% absolute bioavailability relative to injectable diazepam in healthy adults.	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 (not rescue duration)	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.	Midazolam median 2.1–6.2 hours; active 1-hydroxymidazolam 2.7–7.2 hours in Nayzilam studies.	Diazepam about 46 hours and active desmethyldiazepam about 71 hours after a 15-mg rectal dose.	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.
Clinical endpoint / 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. [5] [6] [1]	Treatment success: seizure termination within 10 minutes after the initial blinded dose and no seizure recurrence from 10 minutes through 6 hours. [7] [2]	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. [5] [6] [3]	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. [5] [6] [4]
Absolute effect	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. [5] [6] [1]	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%. [7] [2]	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). [5] [6] [3]	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. [5] [6] [4]
U.S. product labels	Open Valtoco DailyMed label (PDF) ↗	Open Nayzilam DailyMed label (PDF) ↗	Open Representative source · diazepam rectal gel — generic DailyMed label (PDF) ↗ Diastat / Diastat AcuDial rectal gel — FDA brand label (2023, PDF) ↗	Open Libervant DailyMed label (PDF) ↗

Valtoco dosing by age and weight

Use the labeled age and weight band. The 15- and 20-mg doses require two devices, with one spray in each nostril.

Age	Weight	Dose	Device / administration
2–5 years	6–11 kg	5 mg	One 5-mg device. One spray in one nostril.
	12–22 kg	10 mg	One 10-mg device. One spray in one nostril.
	23–33 kg	15 mg	Two 7.5-mg devices. One spray in each nostril.
6–11 years	10–18 kg	5 mg	One 5-mg device. One spray in one nostril.
	19–37 kg	10 mg	One 10-mg device. One spray in one nostril.
	38–55 kg	15 mg	Two 7.5-mg devices. One spray in each nostril.
	56–74 kg	20 mg	Two 10-mg devices. One spray in each nostril.
12 years and older	14–27 kg	5 mg	One 5-mg device. One spray in one nostril.
	28–50 kg	10 mg	One 10-mg device. One spray in one nostril.
	51–75 kg	15 mg	Two 7.5-mg devices. One spray in each nostril.
	76 kg and up	20 mg	Two 10-mg devices. One spray in each nostril.

Only label-listed weight bands are shown. Do not extrapolate a dose outside these bands; confirm the prescribed dose and device strength. The 2–5-year table ends at 33 kg and the 6–11-year table at 74 kg.

Valtoco — U.S. dosing section ↗

Diastat / diazepam rectal gel dosing by age and weight

The label uses 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 dose. Use the prescribed, pharmacy-set rectal delivery system.

Age	Weight	Dose	Device / administration
2–5 years	6–10 kg	5 mg	One rectal delivery system set to 5 mg.
	11–15 kg	7.5 mg	One rectal delivery system set to 7.5 mg.
	16–20 kg	10 mg	One rectal delivery system set to 10 mg.
	21–25 kg	12.5 mg	One rectal delivery system set to 12.5 mg.
	26–30 kg	15 mg	One rectal delivery system set to 15 mg.
	31–35 kg	17.5 mg	One rectal delivery system set to 17.5 mg.
	36–44 kg	20 mg	One rectal delivery system set to 20 mg.
6–11 years	10–16 kg	5 mg	One rectal delivery system set to 5 mg.
	17–25 kg	7.5 mg	One rectal delivery system set to 7.5 mg.
	26–33 kg	10 mg	One rectal delivery system set to 10 mg.
	34–41 kg	12.5 mg	One rectal delivery system set to 12.5 mg.
	42–50 kg	15 mg	One rectal delivery system set to 15 mg.
	51–58 kg	17.5 mg	One rectal delivery system set to 17.5 mg.
	59–74 kg	20 mg	One rectal delivery system set to 20 mg.
12 years and older	14–25 kg	5 mg	One rectal delivery system set to 5 mg.
	26–37 kg	7.5 mg	One rectal delivery system set to 7.5 mg.
	38–50 kg	10 mg	One rectal delivery system set to 10 mg.
	51–62 kg	12.5 mg	One rectal delivery system set to 12.5 mg.
	63–75 kg	15 mg	One rectal delivery system set to 15 mg.
	76–87 kg	17.5 mg	One rectal delivery system set to 17.5 mg.
	88–111 kg	20 mg	One rectal delivery system set to 20 mg.

Only label-listed weight bands are shown; do not extrapolate beyond them. The label also permits a prescribed 2.5-mg partial replacement dose when some of the first dose is expelled; this is not a separate age–weight band. Older or debilitated patients may require a lower prescribed dose.

Diastat / diazepam rectal gel — U.S. dosing section ↗

Libervant dosing by age and weight

U.S. labeling is limited to children 2 through 5 years of age. Select one whole buccal film by body weight.

Age	Weight	Dose	Device / administration
2–5 years	6–10 kg	5 mg	One 5 mg film inside the cheek.
	11–15 kg	7.5 mg	One 7.5 mg film inside the cheek.
	16–20 kg	10 mg	One 10 mg film inside the cheek.
	21–25 kg	12.5 mg	One 12.5 mg film inside the cheek.
	26–30 kg	15 mg	One 15 mg film inside the cheek.

Only label-listed weight bands are shown; do not extrapolate outside 6–30 kg. Do not split, chew, or intentionally swallow the film, or administer with liquids.

Libervant — U.S. dosing section ↗

Trial endpoints and exposure

Valtoco

diazepam nasal spray

Pharmacokinetic bridge

Endpoint: 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. [5] [6] [1]
Absolute effect: 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. [5] [6] [1]
Confidence intervals: The current U.S. label does not report confidence intervals for the bridged rectal-gel endpoint differences. [1]
Discontinuations: No Valtoco-specific controlled efficacy-trial discontinuation rate is available. In the bridged rectal-gel controlled trials, adverse-event discontinuations were 2% with diazepam rectal gel and 2% with placebo. [1]
Exposure: Current label pooled safety population: 255 patients age 2 and older; 143 received Valtoco for at least 1 year. Published 2021 open-label safety study: 163 treated patients age 6–65; 133 had at least 12 months of exposure. These are different study populations. [1] [8]

Nayzilam

midazolam nasal spray

Direct pivotal trial

Endpoint: Treatment success: seizure termination within 10 minutes after the initial blinded dose and no seizure recurrence from 10 minutes through 6 hours. [7] [2]
Absolute effect: 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%. [7] [2]
The trial publication reports placebo treatment success as 34.4% (p=0.0109); the displayed 34.3% follows the U.S. label. [7] [2]
Confidence intervals: Treatment-success 95% CI: 45.3%–62.2% with Nayzilam and 23.0%–45.7% with placebo. The label does not report a confidence interval for the between-group absolute difference. [2]
Discontinuations: Published trial: 16/292 patients (5.5%) discontinued for a treatment-emergent adverse event during the test-dose phase; none did so during the comparative phase. Tolerability screening before randomization limits generalizability. [7]
Exposure: 292 patients received an in-clinic test dose; 262 were randomized and 201 treated an outpatient cluster (134 Nayzilam, 67 placebo). The primary endpoint covered 6 hours; time to next seizure was evaluated through 24 hours. [2] [7]

Diastat / diazepam rectal gel

diazepam rectal gel

Direct pivotal trial

Endpoint: 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. [5] [6] [3]
Absolute effect: 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). [5] [6] [3]
Confidence intervals: The current U.S. label reports p-values but not confidence intervals for these endpoint differences. [3]
Discontinuations: Controlled trials: 2% with diazepam rectal gel and 2% with placebo discontinued for adverse events. Across 573 exposed patients, 1.4% discontinued because of an adverse event. [3]
Exposure: Study 1: 125 randomized, 91 treated (47 children, 44 adults); observation lasted 12 hours in children and 24 hours in adults. Study 2: 158 enrolled, 114 treated (56 diazepam, 58 placebo); observation lasted 12 hours. [3] [5] [6]

Libervant

diazepam buccal film

Pharmacokinetic bridge

Endpoint: 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. [5] [6] [4]
Absolute effect: 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. [5] [6] [4]
Confidence intervals: The current U.S. label does not report confidence intervals for the bridged rectal-gel endpoint differences. [4]
Discontinuations: No Libervant-specific randomized efficacy-trial discontinuation rate is available. The label reports the bridged rectal-gel controlled-trial rate of 2% in each group. [4]
Exposure: Current label pooled safety population: 197 patients; 107 received Libervant for at least 6 months and 48 for at least 1 year. These counts are not a randomized efficacy cohort. Bridged rectal-gel efficacy observations lasted 12–24 hours. [4] [5] [6]

Know the emergency boundary before a cluster occurs. Call emergency services when the written plan directs, when seizures continue despite prescribed treatment, when the episode differs from prior clusters, or when duration, recovery, color, breathing, injury, pregnancy, or caregiver concern makes the event unsafe. A convulsive seizure lasting 5 minutes or recurrent convulsions without recovery is status epilepticus until proven otherwise and requires an emergency protocol.

Study references and U.S. labels

Indications and label PDFs checked 26 September 2026. Other dosing and trial fields last reviewed 15 September 2026.