VALTOCO gives
patients and care
partners confidence
anytime, anywhere

swipe
Rapid- 4 minutes

4-minute median time from VALTOCO administration to seizure cessation2,*,†

  • Seizures treated in the first 5 minutes with VALTOCO stopped within a median of 2
    minutes3

Time to administer and onset of action

icon

Early intervention with VALTOCO

icon
Reliable- 1 Dose

87% of seizure episodes used a single dose of VALTOCO over a 24-hour period5,*

  • 89% of seizure episodes in patients aged 6 to 17 years6

Use of single doses of VALTOCO over 24 hours

icon
Ready- 1 Hour

A majority of patients returned to their usual selves within 1 hour of administration of VALTOCO9,‡

  • Treatment-related somnolence was reported in 1.8% of patients5

The number of seizure-free days between treated seizure clusters doubled over a 12-month period in patients using VALTOCO10,§

Return to self and mean sedation levels

icon

Analysis of time between treated seizure clusters

icon

*This was an exploratory analysis; the study did not have prespecified efficacy endpoints.5

Median time to seizure cessation of 4 minutes (range, -1-1151 minutes).2

59% of patients returned to their usual selves within 60 minutes of administration of VALTOCO as recorded in patient and caregiver surveys.9

§SEIVAL was measured as the time between VALTOCO doses using seizure diary data from the open-label safety study. Seventy-six of the 163 patients (47%) who received >_1 dose of VALTOCO in the study had >_1 SEIVAL in each of Periods 1, 2, 3, and 4 and were included in the consistent cohort for Periods 1-4. Retreatments, defined as second doses given within 24 hours of the first doses, were eliminated from the analysis.10

VALTOCO sprayer

Only VALTOCO uses Intravail®
technology for rapid and reliable
absorption of diazepam12,13

swipe

VALTOCO was formulated to address the principal limitations of intranasal drug delivery. Intravail® technology facilitates increased drug absorption across the nasal mucosa by increasing permeability of cell membranes and temporarily loosening tight junctions between cells, allowing the drug to pass through.14

Administration of VALTOCO results
in rapid absorption of diazepam with nearly
100% bioavailability1,12

Therapeutic plasma levels of VALTOCO sustained for 24 hours 1,12
Therapeutic plasma levels of VALTOCO sustained for 24 hours

Reduction in seizure activity can occur at a diazepam concentration as low as 30 ± 15 ng/mL15,16

Predictable pharmacokinetics with low interpatient and intrapatient variability17

VALTOCO demonstrated 2- to 4-fold less pharmacokinetic variablity than Diastat® (diazepam rectal gel) regardless
of patient weight17

Pharmacokinetic variability profiles of VALTOCO and Diastat 17

AUC, area under the curve; Cmax, maximum serum concentration.

90% CI

Pharmacokinetic variability profiles of VALTOCO and Diastat
  • VALTOCO pharmacokinetics were not notably altered when administered during seizures vs under normal conditions11

See how VALTOCO works to optimize diazepam nasal delivery

Learn how the unique formulation of VALTOCO optimizes diazepam for nasal delivery, and how it helps patients manage episodes of frequent seizure activity whenever, wherever.

Video
Sprayer icon

VALTOCO was deemed clinically superior in administration to Diastat® (diazepam rectal gel) by the US Food and Drug Administration (FDA)18,19

The intranasal route of administration of VALTOCO provides a major contribution to patient care over the rectal
route of administration by providing a significantly improved ease of use.18

Because of this, the FDA has determined that VALTOCO deserves orphan drug exclusivity.19

VALTOCO was
strongly
preferred in
a patient survey9,*

swipe

*Data collected from patient diaries and patient and care partner surveys.9

90% icon

90% said it was “extremely easy” or “very easy” to train others to administer VALTOCO

87% icon

87% felt more comfortable being treated in public with VALTOCO than with diazepam rectal gel

84% icon

84% said they would prefer using VALTOCO as their seizure rescue exclusively in the future

79% icon

79% were very comfortable doing activities outside the home with VALTOCO available

Improvements in seizure
worry and social functioning20 swipe

PATIENTS WITH EPILEPSY
Reductions in Seizure Worry   Improvements in Social Functioning

Mean total QOLIE-31-P scores increased from day 0 (n=71) to day 365 (n=53) by 5.2 points (from 57.3 to 62.5), which also exceeded the MIC threshold of 5.19.

MIC, minimally important change; QOLIE-31-P, Quality of Life in Epilepsy—Problems.

Crowd of people
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 6 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, including Boxed Warning.

IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING

icon

IMPORTANT SAFETY INFORMATION,  INCLUDING BOXED WARNING

icon
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, including Boxed Warning.

References

1. Valtoco. Package insert. Neurelis Inc; 2023; 2. Data on file. REF-01245. Neurelis Inc; 3. Data on file. REF-01288. Neurelis Inc; 4. Desai J, Hogan RE, Wheless JW, et al; DIAZ.001.05 Study Group. Timing to administration and ease of dosing of diazepam nasal spray rescue therapy for seizure clusters: results from a phase 3, long-term, open-label, repeat-dose safety study. Poster presented at: American Academy of Neurology 74th Annual Meeting; April 2-7, 2022; Seattle, WA; 5. 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; 6. Tarquinio D, Dlugos D, Wheless JW, et al. Safety of Valtoco® (diazepam nasal spray) in children and adolescents with epilepsy: final subgroup results from a phase 3, long-term, open-label, repeat-dose safety study. Poster presented at: Child Neurology Society 50th Annual Meeting; September 29 – October 2, 2021; Boston, MA; 7. Sperling MR, Wheless JW, Hogan RE, et al; DIAZ.001.05 Study Group. Use of second doses of Valtoco® (diazepam nasal spray) across 24 hours after the initial dose for out-of-hospital seizure clusters: results from a phase 3, open-label, repeat-dose safety study. Epilepsia. 2022;63(4):836-843. doi:10.1111/epi.17177; 8. Data on file. REF-01292. Neurelis Inc; 9. 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; 10. 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; 11. 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; 12. 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; 13. 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; 14. 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; 15. Milligan N, Dhillon S, Richens A, Oxley J. Rectal diazepam in the treatment of absence status: a pharmacodynamic study. J Neurol Neurosurg Psychiatry. 1981;44(10):914-917. doi:10.1136/jnnp.44.10.914; 16. Dhir A, Rogawski MA. Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats. Epilepsia. 2018;59(5):935-944. doi:10.1111/epi.14069; 17. 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; 18. Woodcock J; US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER). Petition Response Letter from FDA CDER to Arent Fox LLP. Docket No. FDA-2019-P-5121. January 10, 2020. Accessed January 5, 2023. https://www.regulations.gov/document?D=FDA-2019-P-5121-0011; 19. Clinical superiority findings: 2019: Neurelis Pharmaceuticals, Inc. for Valtoco (diazepam nasal spray). US Food and Drug Administration. Accessed January 5, 2023. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/clinical-superiority-findings; 20. 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

icon

Get Copay Card

Eligible Patients

Pay as little as $20
Terms and conditions apply

See Copay Details
icon

Order Demo Kit

Learn How to Use VALTOCO

Includes demo sprayer and dosing information

Order Kit Now