Proven Safety and Tolerability

See how VALTOCO® (diazepam nasal spray) is generally safe and well tolerated.1

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Treatment-Related Adverse Reactions Were Mild-to-Moderate and Transient2,3

In two open-label repeat-dose clinical studies of patients with epilepsy 6 years of age and older (N=190)1

Most frequent local treatment-related adverse reactions

Nasal discomfort   6%
Epistaxis   3%
Nasal congestion   3%
Dysgeusia   2%

Data from an open-label, repeat-dose pharmacokinetic study in epilepsy subjects under seizure and normal conditions (Study 04) and a 12-month, open-label, repeat-dose safety study in epilepsy patients (Study 05).4,5

No Discontinuations or Serious Adverse Events Were Considered Treatment Related2,6*

60%

of patients received VALTOCO for at least 6 months and 35% at least 1 year1

Additional Safety Information

The safety of VALTOCO is also supported by double-blind, placebo-controlled trials with diazepam rectal gel, using the same dosing strategy1,7

*The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.1

In clinical studies of adults and children 6 years of age and older.

Safety Outcomes From a Clinical Study

A phase 1, open-label study assessed the pharmacokinetics and safety of VALTOCO in patients (N=57) with epilepsy2,6

Treatment-Emergent Adverse Events (TEAEs) Were Reported Regardless of Causality2

  • The most common treatment-related TEAEs, defined as those occurring in ≥2 subjects, were dysgeusia (5.3%), nasopharyngitis (3.5%), and nasal discomfort (3.5%)2,6
  • No changes in respiratory rate were observed2,6
  • There were no reported TEAEs of somnolence2,6

Data as of October 20, 2019, from an open-label, repeat-dose pharmacokinetic study in epilepsy subjects under seizure and normal conditions (Study 04).4

Safety Outcomes From a Long-term, Repeat-Dose Study

Ongoing phase 3, open-label, long-term, repeat-dose study assessed the safety of VALTOCO in patients (N=132) with epilepsy (Study 05)8

  • In subjects with epilepsy 6 to 65 years of age8
  • Study design was for 12-month treatment period with extensions permitted8
  • Safety of VALTOCO was the primary study objective8
  • Treatment-emergent adverse events (TEAEs) were reported regardless of causality8
  • The most common treatment-related TEAEs, defined as those occurring in ≥2 subjects, were nasal discomfort (5.3%), headache (3%), epistaxis (2.3%), cough (1.5%), eye irritation (1.5%), lacrimation increased (1.5%), rhinalgia (1.5%), and somnolence (1.5%)8
  • High subject retention rate with no treatment-related discontinuations8
  • No serious adverse events were considered to be treatment related8

Single Dose Used for Vast Majority of Episodes9

A phase 3, open-label, repeat-dose, safety study in subjects with epilepsy who experience episodes of frequent seizure activity assessed the safety of diazepam after repeat intranasal doses of VALTOCO over a 12-month period3

Percentage of seizure episodes for which a single dose of VALTOCO was used over the course of 24 hours (N=3,914)9

with a single dose
VALTOCO single dose chart
  • Ongoing open-label, repeat-dose safety study9
    • 177 patients with epilepsy, ages 6 to 65 years of age9
    • 3,914 seizure episodes were treated with VALTOCO9
    • Exploratory analysis to assess the safety of diazepam. Study did not have prespecified efficacy endpoints9
  • 12-month treatment period for each patient5

A second dose may be given at least 4 hours after the initial dose, if required 1

more information on seizure treatment

VALTOCO is designed for immediate use and available in 4 treatment doses.

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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. 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; doi: 10.1111/epi.16506. 3. Wheless JW, Sperling MR, Segal EB, et al. Safety of Valtoco (NRL-1; diazepam nasal spray) in patients with epilepsy: interim results from a phase 3, open-label, 12-month repeat dose study. Poster presented at: Academy of Managed Care Pharmacy 2020 Annual Meeting; April 21-24, 2020; Houston, TX. 4. Data on file. REF-00390. Neurelis, Inc. 5. Data on file. REF-00208. Neurelis, Inc. 6. Tarquinio D, Hogan RE, Sperling MR, et al. Safety and tolerability of NRL-1, an intranasal formulation of diazepam, in subjects with epilepsy in a phase 1, open-label study: focus on adverse events relevant to clinicians and patients (2044). Neurology. 2020;94(suppl 15). 7. Diastat (diazepam rectal gel) Prescribing Information. Valeant Pharmaceuticals. 8. Wheless JW, Sperling MR, Liow K, et al. Safety of Valtoco (NRL-1; diazepam nasal spray) in patients with epilepsy: interim results from a phase 3, open-label, 12-month, repeat-dose study. Poster presented at: American Epilepsy Society 2019 Annual Meeting; December 6-10, 2019; Baltimore, MD. 9. Data on file. REF-00643. Neurelis, Inc.