Diazepam nasal spray (Valtoco®) is a benzodiazepine. FDA Approved Indication(s)
Valtoco is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., 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.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Valtoco is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Epilepsy with Seizure Cluster Episodes (must meet all):

1. Diagnosis of partial or generalized epilepsy;
   
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 6 years;
   4. Member is experiencing stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures);
2. Currently on a stable regimen of antiepileptic drugs (AEDs) (e.g., lamotrigine, gabapentin, topiramate, oxcarbazepine);
3. Documentation supports inability to use diazepam rectal gel (e.g., request is for use at school where rectal medications cannot be administered);
4. Dose does not exceed 2 doses per single episode (not to exceed 1 episode every 5 days or 5 episodes per month) (refer to section V for age and weight specific dosing). Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):

5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 1 of 9

   CLINICAL POLICY Diazepam Nasal Spray CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Epilepsy with Seizure Cluster Episodes (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Valtoco for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   
   3. If request is for a dose increase, new dose does not exceed 2 doses per single episode (not to exceed 1 episode every 5 days or 5 episodes per month) (refer to section V for age and weight specific dosing). Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents Page 2 of 9

    CLINICAL POLICY Diazepam Nasal Spray IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AED: antiepileptic drug FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose 0.5 mg/kg/dose diazepam rectal gel (Diastat®) Age-based dosing, administered rectally: 2-5 years: 0.5 mg/kg/dose 6-11 years: 0.3 mg/kg/dose 12 years and older: 0.2 mg/kg/dose phenytoin (Dilantin®) carbamazepine (Tegretol®) oxcarbazepine (Tegretol®) A second dose, when required, may be given 4-12 hours after the first dose. Generalized tonic-clonic and complex partial • Initial dose is 100 mg (2 tablets) PO TID; may adjust dose every 7 to 10 days as necessary • Maintenance dosage: 300 to 400 mg/day Partial, generalized, and mixed types • Age 12 years and older: Initial dose is 200 mg PO BID for the first week; may increase by adding up to 200 mg/day in 3 or 4 divided doses at weekly intervals to the minimum effective level (usually 800 to 1,200 mg/day) Partial seizure, monotherapy • Age 12-16 years: Initial dosage 8 to 10 mg/kg PO QD on an empty stomach, May increase in 8 to 10 mg/kg/day increments at weekly intervals to achieve a target dose over 2 to 3 weeks.
    o Target maintenance dose is based on weight; (20-29 kg, 900 mg/day) (29.1- 39 kg, 1,200 mg/day); and (greater than 39 kg, 1,800 mg/day)
    • Age 17 to 18 years: Initial dosage is 600 mg/day PO QD for 1 week on an empty 600 mg/day Children age 12 to 15 years: 1,000 mg/day
    Children older than age 15 years: 1,200 mg/day
    Adults: 1,200 mg/day; rarely, up to 1,600 mg/day may be given Monotherapy Age 12 to 16 years: 600 mg/day
    Age 17 years and older: 2,400 mg/day Adjunct Age 12 to 16 years: 600 mg/day Page 3 of 9

    Dose Limit/ Maximum Dose Age 17 years and older: 1,200 mg/day CLINICAL POLICY Diazepam Nasal Spray Drug Name Dosing Regimen stomach. May increase in 600 mg/day increments at weekly intervals to 1,200 to 2,400 mg/day • Adult initial dosage: 600 mg/day in 2 divided doses. Increase every third day by 300 mg/day to achieve a dose of 1,200 mg/day Partial seizure; adjunct • Age 12 to 16 years: Initial dosage is 8 to 10 mg/kg/day PO in 2 divided doses o Maintenance dosage should be achieved over 2 weeks, and is dependent upon patient weight: (20 to 29 kg, 900 mg/day); (29.1 to 39 kg, 1200 mg/day); and (greater than 39 kg, 1,800 mg/day) • Age 17 and older: initial dosage is 300 mg PO BID; may increase weekly by up to 600 mg/day Epilepsy • Pediatrics: 15 to 50 mg PO BID or TID • Adults: 50 to 100 mg tablet PO BID or TID phenobarbital gabapentin (Neurontin®) Partial seizure; adjunct • Age 12 years and older: Initial dose is 300 mg PO TID • Maintenance is 300 to 600 mg PO TID pregabalin (Lyrica®) Partial seizure • Age 12-16; Adjunct:
    o Weight below 30 kg initial dose is 3.5 mg/kg/day PO in 2 or 3 divided doses o Weight above 30 kg initial dose is 2.5 mg/kg/day PO in 2 or 3 divided doses • Age 17 years and older; Adjunct: Initial dose is 150 mg/day orally in 2 or 3 divided doses Doses up to 2,400 mg/day have been well tolerated; doses of 3,600 mg/day have been administered to a small number of patients for a short duration Age 12 to 16 years with weight below 30 kg: 14 mg/kg/day in 2 or 3 divided doses Age 12 to 16 years with weight above 30 kg and ages 17 and older: 10 mg/kg/day or 600 mg/day in 2 or 3 divided doses Page 4 of 9

    Dose Limit/ Maximum Dose 60 mg/kg/day or less with a therapeutic serum range of 50 to 100 mcg/mL 400 mg/day
    CLINICAL POLICY Diazepam Nasal Spray Drug Name Dosing Regimen valproic acid (Depakote®) topiramate (Topamax®) Complex partial epileptic seizure • Monotherapy: Initial dose is 10 to 15 mg/kg/day PO (give in 2 to 3 divided doses if total daily dose exceeds 250 mg), may increase dosage 5 to 10 mg/kg/day at 1-week intervals to achieve optimal clinical response • Adjunct: May be added to the regimen at an initial dose of 10 to 15 mg/kg/day PO (give in 2 to 3 divided doses if total daily dose exceeds 250 mg); may increase dosage 5 to 10 mg/kg/day at 1-week intervals to achieve optimal clinical response Partial seizure • Age 12 years and older; Monotherapy: Initial dosage is 25 mg PO BID (morning and evening) for the first week; second week, 50 mg PO BID; third week, 75 mg PO BID; fourth week, 100 mg PO BID; fifth week, 150 mg PO BID; sixth week, 200 mg PO BID • Age 12 to 16 years; Adjunct: Initial dosage is 25 mg or less (1 to 3 mg/kg/day) PO at bedtime for the first week, then increase dosage by 1 to 3 mg/kg/day (in 2 divided doses) at 1 to 2 week intervals to the usual effective dosage of 5 to 9 mg/kg/day. • Age 17 years and older; Adjunct: Initial dosage is 25 to 50 mg/day PO; may increase dosage by 25 to 50 mg/day at 1- week intervals to the usual maintenance dose of 200 to 400 mg/day in 2 divided doses; titrating in increments of 25 mg/day every week may delay the time to reach an effective dose; doses above 400 mg/day have not been shown to improve responses Tonic-clonic seizure, primary generalized • Age 12 years and older; Monotherapy: First week initial dosage is 25 mg PO BID; second week, 50 mg PO BID; third Page 5 of 9

    CLINICAL POLICY Diazepam Nasal Spray Drug Name Dosing Regimen Dose Limit/ Maximum Dose week, 75 mg PO BID; fourth week, 100 mg PO BID; fifth week, 150 mg PO BID; sixth week 200 mg PO BID (usual maintenance dose) • Age 12 to 16 years; Adjunct: Initial dosage is 25 mg or less (1 to 3 mg/kg/day) PO at bedtime for the first week, then increase dosage by 1 to 3 mg/kg/day (in 2 divided doses) at 1 to 2 week intervals to the usual effective dosage of 5 to 9 mg/kg/day in 2 divided doses • Age 17 years and older; Adjunct: Initial dosage is 25 to 50 mg/day PO; may increase dosage by 25 to 50 mg/day at 1- week intervals to the usual maintenance dose of 400 mg/day in 2 divided doses; titrating in increments of 25 mg/day every week may delay the time to reach an effective dose Partial seizure & tonic-clonic seizure, primary generalized
    • Age 4 to 16 years; Adjunct:
    o Weight 20 to 40 kg: Initial dose is 250 mg PO BID; titration, increase by increments of 500 mg/day in 2 divided doses every 2 weeks o Weight greater than 40 kg: Initial dose is 500 mg PO BID; titration, increase by increments of 1,000 mg/day every 2 weeks in 2 divided doses • Age 16 years and older; Adjunct: Initial dose is 500 mg PO BID; titration, may increase by increments of 1,000 mg/day every 2 weeks in 2 divided doses
    levetiracetam (Keppra®) Age 4 to 16 years with weight 20 to 40 kg: 1,500 mg/day Age 4 to 16 years with weight above 40 kg, as well as age 16 years and older: 3,000 mg/day Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings
    • Contraindication(s): acute narrow-angle glaucoma, known hypersensitivity to diazepam • Boxed warning(s): concomitant use with opioids; abuse, misuse, and addiction; dependence and withdrawal reactions Page 6 of 9

    CLINICAL POLICY Diazepam Nasal Spray Appendix D: General Information
    • Seizure clusters can be defined as multiple seizures that occur within a short period of time. These seizures will happen in an increased frequency from the patient’s normal seizure activity. Thus, they are distinguishable from a person's typical seizure pattern. The definition for a specific time period varies. Various studies use the following time frames: two to four seizures per < 48 hours; 3 seizures per 24 hours; or two generalized tonic-clonic or three complex partial seizures in 4 hours. Seizure clusters are also known as acute-repetitive seizures, serial seizures, crescendo seizures, and seizure flurries, which highlight the repetitive nature of the seizures. Seizure clusters are a form of seizure emergency that have potential to evolve into prolonged seizures and status epilepticus. V. Dosage and Administration
    Maximum Dose 2 doses/single episode; do not treat more than 1 episode every 5 days or more than 5 episodes/month
    Indication Seizure clusters in patients with epilepsy Dosing Regimen Spray initial dose into nostril. If no response 4 hours after the initial dose, a second dose may be given. The recommended dose of Valtoco nasal spray is 0.2 mg/kg or 0.3 mg/kg, depending on the patient’s age and weight. The following table provides the acceptable weight ranges for each dose and age category, such that patients will receive between 90% and 180% of the calculated recommended dose. Administration 6-11 years (0.3 mg/kg) Weight (kg) 10-18 Dose ≥ 12 years (0.2 mg/kg) Weight (kg) 14-27 19-37 28-50 38-55 51-75 56-74 ≥ 76 Dose (mg)

    of Nasal

    Spray Devices

    of

    Sprays 5 10 15 20 One 5 mg device One 10 mg device Two 7.5 mg devices Two 10 mg devices 1 spray in one nostril
    1 spray in one nostril 1 spray in each nostril 1 spray in each nostril VI. Product Availability
    Nasal spray: 5 mg/0.1 mL, 7.5 mg/0.1 mL, 10 mg/0.1 mL VII.