# VALTOCO (diazepam nasal spray) CIV

> VALTOCO is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 2 years of age and older. See information about VALTOCO for HCPs, including full [Prescribing Information](https://www.valtoco.com/PI), Boxed Warning, and [Instructions for Use](https://valtoco.com/VALTOCO_Instructions_For_Use.pdf).

> This site is intended for Health Care Professionals. For the Patient version of the site please visit https://www.valtoco.com/.


## Indication
VALTOCO (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 2 years of age and older.

## IMPORTANT SAFETY INFORMATION

> **WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS**
> - **Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.**
> - **The use of benzodiazepines, including VALTOCO, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing VALTOCO and throughout treatment, assess each patient's risk for abuse, misuse, and addiction.**
> - **The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although VALTOCO is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of VALTOCO may precipitate acute withdrawal reactions, which can be life-threatening. For patients using VALTOCO more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue VALTOCO.**

**Contraindications:** VALTOCO is contraindicated in patients with:
- Hypersensitivity to diazepam
- Acute narrow-angle glaucoma

**Central Nervous System (CNS) Depression**

Benzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits.

The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner.

**Suicidal Behavior and Ideation**

Antiepileptic drugs (AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior.

**Glaucoma**

Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.

**Neonatal Sedation and Withdrawal Syndrome**

Use of VALTOCO late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to VALTOCO during pregnancy or labor for signs of sedation and monitor neonates exposed to VALTOCO during pregnancy for signs of withdrawal; manage these neonates accordingly.

**Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative**

VALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including "gasping syndrome," can occur in neonates and low-birth-weight infants treated with benzyl alcohol–preserved drugs, including VALTOCO. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known.

**Adverse Reactions**

The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.

**Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance.**

To report SUSPECTED ADVERSE REACTIONS, contact Neurelis, Inc. at 1-866-696-3873 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see full [Prescribing Information](https://www.valtoco.com/sites/default/files/pdf/Prescribing_Information.pdf), including Boxed Warning.

**References**

1. Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia. 2018;59(12):2179-2193. doi:10.1111/epi.14596
2. Detyniecki K, O'Bryan J, Choezom T, et al. Prevalence and predictors of seizure clusters: a prospective observational study of adult patients with epilepsy. Epilepsy Behav. 2018;88:349-356. doi:10.1016/j.yebeh.2018.09.035
3. Haut SR, Shinnar S, Moshe SL, O'Dell C, Legatt AD. The association between seizure clustering and convulsive status epilepticus in patients with intractable complex partial seizures. Epilepsia. 1999;40(12):1832-1834. doi:10.1111/j.1528-1157.1999.tb01607.x
4. Haut SR, Shinnar S, Moshe SL. Seizure clustering: risks and outcomes. Epilepsia. 2005;46(1):146-149. doi:10.1111/j.0013-9580.2005.29004.x
5. Zhong R, Chen Q, Zhang X, Lin W. The occurrence of seizure clusters in patients with epilepsy is partly determined by epilepsy severity: a single-center retrospective observational study. Front Neurol. 2021;12:794086. doi:10.3389/fneur.2021.794086
6. Penovich PE, Buelow J, Steinberg K, Sirven J, Wheless J. Burden of seizure clusters on patients with epilepsy and caregivers: survey of patient, caregiver, and clinician perspectives. Neurologist. 2017;22(6):207-214. doi:10.1097/NRL.0000000000000140
7. Munger Clary HM, Giambarberi L, Floyd WN, Hamberger MJ. Afraid to go out: poor quality of life with phobic anxiety in a large cross-sectional adult epilepsy center sample. Epilepsy Res. 2023;190:107092. doi:10.1016/j.eplepsyres.2023.107092
8. Salinsky MC, Wegener K, Sinnema F. Epilepsy, driving laws, and patient disclosure to physicians. Epilepsia. 1992;33(3):469-472. doi:10.1111/j.1528-1157.1992.tb01693.x
9. Sillanpaa M, Schmidt D. Seizure clustering during drug treatment affects seizure outcome and mortality of childhood-onset epilepsy. Brain. 2008;131(pt 4):938-944. doi:10.1093/brain/awn037
10. Sutula TP, Hagen J, Pitkanen A. Do epileptic seizures damage the brain? Curr Opin Neurol. 2003;16(2):189-195. doi:10.1097/01.wco.0000063770.15877.bc
11. Naylor DE. Treating acute seizures with benzodiazepines: does seizure duration matter? Epileptic Disord. 2014;16(spec no 1):S69-S83. doi:10.1684/epd.2014.0691
12. Niquet J, Baldwin R, Suchomelova L, et al. Benzodiazepine-refractory status epilepticus: pathophysiology and principles of treatment. Ann NY Acad Sci. 2016;1378(1):166-173. doi:10.1111/nyas.13147
13. O'Dell C, Wheless JW, Cloyd J. The personal and financial impact of repetitive or prolonged seizures on the patient and family. J Child Neurol. 2007;22(5)(suppl):61S-70S. doi:10.1177/0883073807303070
14. Seizure rescue therapies. Epilepsy Foundation. April 14, 2019. https://www.epilepsy.com/treatment/seizure-rescue-therapies.
15. Valtoco. Prescribing Information. Neurelis Inc. https://www.valtoco.com/PI
16. Data on file. REF-01944. Neurelis, Inc.
17. Data on file. REF-01945. Neurelis, Inc.
18. Penovich P, Wheless JW, Hogan RE, et al. Examining the patient and caregiver experience with diazepam nasal spray for seizure clusters: results from an exit survey of a phase 3, open-label, repeat-dose safety study. Epilepsy Behav. 2021;121(pt A):108013. doi:10.1016/j.yebeh.2021.108013
19. Wheless JW, Miller I, Hogan RE, et al; DIAZ.001.05 Study Group. Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy. Epilepsia. 2021;62(10):2485-2495. doi:10.1111/epi.17041
20. Segal EB, Wheless JW, Zafar M, et al; DIAZ.001.008 Study Group. Pharmacokinetics and 180-day safety of diazepam nasal spray in pediatric patients with epilepsy aged 2-5 years. Epilepsia. Published online July 12, 2025. doi:10.1111/epi.18473
21. Hogan RE, Tarquinio D, Sperling MR, et al. Pharmacokinetics and safety of VALTOCO (NRL-1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri-ictal) and nonseizure (interictal) conditions: a phase 1, open-label study. Epilepsia. 2020;61(5):935-943. doi:10.1111/epi.16506
22. Misra SN, Sperling MR, Rao VR, et al. Significant improvements in SEIzure interVAL (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters. Epilepsia. 2022;63(10):2684-2693. doi:10.1111/epi.17385
23. Data on file. REF-02211. Neurelis, Inc.
24. Data on file. REF-02212. Neurelis, Inc.
25. Misra SN, Jarrar R, Stern JM, Becker DA, Carrazana E, Rabinowicz AL. Rapid rescue treatment with diazepam nasal spray leads to faster seizure cluster termination in epilepsy: an exploratory post hoc cohort analysis. Neurol Ther. 2024;13(1):221-231. doi:10.1007/s40268-021-00360-4
26. Dhaliwal JS, Rosani A, Saadabadi A. Diazepam. In: StatPearls. StatPearls Publishing; 2025. https://www.ncbi.nlm.nih.gov/sites/books/NBK537022
27. Greenblatt DJ, Arendt RM, Abernethy DR, Giles HG, Sellers EM, Shader RI. In vitro quantitation of benzodiazepine lipophilicity: relation to in vivo distribution. Br J Anaesth. 1983;55(10):985-989. doi:10.1093/bja/55.10.985
28. Agarwal SK, Kriel RL, Brundage RC, Ivaturi VD, Cloyd JC. A pilot study assessing the bioavailability and pharmacokinetics of diazepam after intranasal and intravenous administration in healthy volunteers. Epilepsy Res. 2013;105(3):362-367. doi:10.1016/j.eplepsyres.2013.02.018
29. Tanimoto S, Koplowitz LP, Lowenthal RE, Koplowitz B, Rabinowicz AL, Carrazana E. Evaluation of pharmacokinetics and dose proportionality of diazepam after intranasal administration of NRL-1 to healthy volunteers. Clin Pharmacol Drug Dev. 2020;9(6):719-727. doi:10.1002/cpdd.767
30. Rabinowicz AL, Carrazana E, Maggio ET. Improvement of intranasal drug delivery with Intravail alkylsaccharide excipient as a mucosal absorption enhancer aiding in the treatment of conditions of the central nervous system. Drugs R D. 2021;21(4):361-369. doi:10.1007/s40268-021-00360-5
31. Hogan RE, Gidal BE, Koplowitz B, Koplowitz LP, Lowenthal RE, Carrazana E. Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers. Epilepsia. 2020;61(3):455-464. doi:10.1111/epi.16449
32. Clinical superiority findings: 2019: Neurelis Pharmaceuticals, Inc. for Valtoco (diazepam nasal spray). US Food and Drug Administration. Accessed November 14, 2025. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/clinical-superiority-findings
33. Cramer JA, Faught E, Davis C, Misra SN, Carrazana E, Rabinowicz AL. Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study. Epilepsy Behav. 2022;134:108811. doi:10.1016/j.yebeh.2022.108811
34. Data on file. REF-01869. Neurelis, Inc.
35. St. Louis EK. Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care. Curr Neuropharmacol. 2009;7(2)106-114. doi:10.2174/157015909788848857
36. Valtoco. Instructions for Use. Neurelis, Inc. https://www.valtoco.com/sites/default/files/pdf/Instructions_For_Use.pdf


## Important Resources
- [Important Safety Information](https://www.valtocohcp.com/#isi_section)
- [Prescribing Information](https://www.valtoco.com/PI)
- [Medication Guide](https://www.valtoco.com/med_guide)
- [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf)
- [For Patients](https://www.valtoco.com/)


## Additional Information
This section act as a guide for navigating the content on https://valtocohcp.com/ based on the page descriptions.

* [Why Treat Quickly?](https://www.valtocohcp.com/why-treat-quickly/): Learn why you should encourage patients to treat seizures as early as possible. Please see full [Prescribing Information](https://www.valtoco.com/PI), including Boxed Warning, and [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf).
* [Why VALTOCO?](https://www.valtocohcp.com/why-valtoco/): Learn about the efficacy of VALTOCO, including information on pharmacokinetics, patient preference, and more. Please see full [Prescribing Information](https://www.valtoco.com/PI), including Boxed Warning, and [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf).
* [Safety](https://www.valtocohcp.com/safety/): Review clinical trial safety data, potential side effects, drug interactions, and warnings and precautions for VALTOCO when prescribing as an immediate-use seizure medication. Please see full [Prescribing Information](https://www.valtoco.com/PI), including Boxed Warning, and [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf).
* [Dosing & Usage](https://www.valtocohcp.com/dosing-and-usage/): Learn about VALTOCO dosing, administration, usage instructions, and how to properly prescribe for patients with episodes of frequent seizures. Please see full [Prescribing Information](https://www.valtoco.com/PI), including Boxed Warning, and [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf).
* [Resources](https://www.valtocohcp.com/resources/): Access resources like Instructions for Use and brochures to educate patients prescribed VALTOCO for episodes of frequent seizures. Please see full [Prescribing Information](https://www.valtoco.com/PI), including Boxed Warning, and [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf).
* [Savings & Support](https://www.valtocohcp.com/savings-and-support/): Discover copay and patient assistance programs to help patients access VALTOCO. Learn about personalized support available from [myNEURELIS](https://www.myneurelis.com/). Please see full [Prescribing Information](https://www.valtoco.com/PI), including Boxed Warning, and [Instructions for Use](https://www.valtoco.com/sites/default/files/VALTOCO_5mg_and_10mg_Instructions_For_Use.pdf).

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