What Are Seizure Clusters?

A seizure cluster, also known as episodes of frequent seizure activity, is often defined as 2 or more seizures in a 24-hour period.1,2

Despite a stable regimen of anti-seizure medications (ASMs), seizures are common and tend to be unpredictable.3,4

Family Fishing

Seizures May Be More Common Than Previously Realized5-7

~40% of patients continue to have seizures despite ASM therapy6,7

Seizure-free rates have not improved in nearly 20 years even though ~28 ASMs are available.6-9

75% say they worry about having a seizure at any time13

Patients Report Unpredictability as the Most Debilitating Aspect of Epilepsy10,11

Even patients well-controlled on medication can unexpectedly experience a seizure.12

stopping seizures icon

Prompt Intervention Is Critical14,15

Most of the time, seizures stop on their own.16 But occasionally, they don't stop and require intervention.17 Patients don't know or can't predict when one will happen or repeat.17

Rescue Treatments Are Effective Yet Underutilized18,19

84% of seizures in pediatric patients were stopped

among users of diazepam rectal gel, and emergency department (ED) visits were avoided19,20

Only 20% of patients say they take rescue medication

when a seizure cluster occurs13

Options for Seizure Rescue Have Been Limited for Many Patients21

Historically, most older children and adults did not use on-hand rescue treatment due to limited options.22,23

on-hand rescue treatment for seizure clusters

Reliable On-Hand Rescue for Episodes of Frequent Seizure Activity1

Together, a daily ASM regimen coupled with an on-hand seizure rescue medication may provide more comprehensive management for patients at risk for repetitive seizures.19

more information on seizure treatment

With nearly complete absorption—97% bioavailability relative to IV diazepam—VALTOCO® (diazepam nasal spray) may be right for your patients.1,24,25

Get to Know VALTOCO

IMPORTANT SAFETY INFORMATION,
INCLUDING BOXED WARNING

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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 only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.

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 read full Prescribing Information, including Boxed Warning, for additional important safety information.

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 only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.

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 read full Prescribing Information, including Boxed Warning, for additional important safety information.

References: 1. VALTOCO® (diazepam nasal spray) Prescribing Information. Neurelis, Inc. 2. Fisher RS, Bartfeld E, Cramer JA. Use of an online epilepsy diary to characterize repetitive seizures. Epilepsy Behav. 2015;47:66-71. 3. Sander JW. Ultimate success in epilepsy—the patient’s perspective. Eur J Neurol. 2005;12(Suppl 4):3-11. 4. Bonnett LJ, Powell GA, Smith CT, Marson AG. Breakthrough seizures—further analysis of the standard versus new antiepileptic drugs (SANAD) study. PLoS One. 2017;12(12):e0190035. 5. Tian N, Boring M, Kobau R, Zack MM, Croft JB. Active epilepsy and seizure control in adults—United States, 2013 and 2015. MMWR Morb Mortal Wkly Rep. 2018;67(15):437-442. 6. National Institute of Neurological Disorders and Stroke. The epilepsies and seizures: hope through research. NIH publication 15-156. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Epilepsies-and-Seizures-Hope-Through. Published April 2015. Updated January 19, 2020. Accessed April 30, 2020. 7. Manford M. Recent advances in epilepsy. J Neurol. 2017;264(8):1811-1824. 8. Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75(3):279-286. 9. Vossler DG, Weingarten M, Gidal BE; American Epilepsy Society Treatments Committee. Summary of antiepileptic drugs available in the United States of America. Epilepsy Curr. 2018;18(4 Suppl 1):1-26. 10. Epilepsy Innovation Institute. Epilepsy Innovation Institute (Ei2): 2016 Community Survey [online] 2017;1-6. http://www.epilepsy.com/sites/core/files/atoms/files/community-survey-report-2016%20V2.pdf. Accessed July 3, 2019. 11. Schulze-Bonhage A, Kuhn A. Unpredictability of seizures and the burden of epilepsy. In: Schelter B, Timmer J, Schulze-Bonhage A, eds. Seizure Prediction in Epilepsy. Wiley-VCH Verlag GmbH & Co. KGaA; 2008. 12. Divino V, Petrilla AA, Bollu V, Velez F, Ettinger A, Makin C. Clinical and economic burden of breakthrough seizures. Epilepsy Behav. 2015;51:40-47. 13. 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. 14. Manno EM. Status epilepticus: current treatment strategies. Neurohospitalist. 2011;1(1):23-31. 15. Gainza-Lein M, Fernandez IS, Jackson M, et al. Association of time to treatment with short-term outcomes for pediatric patients with refractory convulsive status epilepticus. JAMA Neurol. 2018;75(4):410-418. 16. Epilepsy Foundation. What Is a Seizure Emergency? https://www.epilepsy.com/learn/managing-your-epilepsy/understanding-seizures-and-emergencies/what-seizure-emergency. Accessed October 9, 2018. 17. Epilepsy Foundation Greater Chicago. Status Epilepticus. https://www.epilepsychicago.org/epilepsy/seizure-types/status-epilepticus/. Accessed July 9, 2019. 18. Jafarpour S, Hirsch LJ, Gainza-Lein M, Kellinghaus C, Detyniecki K. Seizure cluster: definition, prevalence, consequences, and management. Seizure. 2019;68:9-15. 19. 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(Suppl):61S-70S. 20. Cereghino JJ, Mitchell WG, Murphy J, et al. Treating repetitive seizures with a rectal diazepam formulation: a randomized study. Neurology. 1998;51(5):1274-1282. 21. Hoerth M. Nasal therapy for seizure emergencies. Epilepsy Foundation website. https://www.epilepsy.com/article/2015/9/nasal-therapy-seizure-emergencies. Published September 2015. Accessed April 30, 2020. 22. Kapoor M, Cloyd JC, Siegel RA. A review of intranasal formulations for the treatment of seizure emergencies. J Control Release. 2016;237:147-159. 23. Epilepsy Foundation. Diastat 101. https://www.epilepsy.com/learn/managing-your-epilepsy/using-rescue-treatments/diastat-101. Accessed July 23, 2019. 24. Maglalang PD, Rautiola D, Siegel RA, et al. Rescue therapies for seizure emergencies: new modes of administration. Epilepsia. 2018;59(Suppl 2):207-215. 25. Agarwal SK, Kriel RK, 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;105:362-367.