SYMPAZAN, Clobazam ONFI, Clobazam Form

Clobazam (Onfi®, Sympazan®) is a benzodiazepine. FDA Approved Indication(s) Onfi and Sympazan are indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or 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 Onfi and Sympazan are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Lennox-Gastaut Syndrome (must meet all):

1. Diagnosis of LGS;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 2 years;
   4. Member meets one of the following (a or b): a. Request is for the treatment of a member in a State with limitations on step therapy in certain settings (see Appendix D); b. Failure of 2 preferred agents for LGS (e.g., clonazepam, valproic acid (divalproex), lamotrigine, topiramate, felbamate), unless clinically significant adverse effects are experienced or all are contraindicated;
2. Member meets one of the following (a or b): a. Request is for the treatment of a member in a State with limitations on step therapy in certain settings (see Appendix D); b. For Onfi and Sympazan requests, member must use generic clobazam tablets or oral suspension, unless clinically significant adverse effects are experienced or both are contraindicated;

3. Dose does not exceed both of the following (a and b): a. 40 mg per day; b. 2 tablets per day, 16 mL per day, or 2 films per day. Approval duration:
   Medicaid/HIM – 12 months
   Commercial – 12 months or duration of request, whichever is less Page 1 of 8

   CLINICAL POLICY Clobazam B. Intractable/Refractory Epilepsy (off-label) (must meet all):

4. Diagnosis of intractable/refractory epilepsy;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 2 years;
   4. Member meets one of the following (a or b): a. Request is for the treatment of a member in a State with limitations on step therapy in certain settings (see Appendix D); b. Failure of ≥ 4 anti-seizure drugs (see Appendix B), unless clinically significant adverse effects are experienced or all are contraindicated;
5. Member meets one of the following (a or b): a. Request is for the treatment of a member in a State with limitations on step therapy in certain settings (see Appendix D); b. For Onfi and Sympazan requests, member must use generic clobazam tablets or oral suspension, unless clinically significant adverse effects are experienced or both are contraindicated;
6. Dose does not exceed both of the following (a and b): a. 40 mg per day; b. 2 tablets per day, 16 mL per day, or 2 films per day. Approval duration:
   Medicaid/HIM – 12 months
   Commercial – 12 months or duration of request, whichever is less C. Dravet Syndrome (off-label) (must meet all):
7. Diagnosis of Dravet syndrome;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 2 years;
   4. For Onfi and Sympazan requests, member must use generic clobazam tablets or oral suspension, unless clinically significant adverse effects are experienced or both are contraindicated;
8. Dose does not exceed 2 mg/kg per day. Approval duration:
   Medicaid/HIM – 12 months
   Commercial – 12 months or duration of request, whichever is less D. 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: Page 2 of 8

   CLINICAL POLICY Clobazam 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.
    II. Continued Therapy A. All Indications in Section I (must meet all):
11. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Onfi or Sympazan for a covered indication and has received this medication for at least 30 days;
    2. Member is responding positively to therapy;
    3. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. LGS or intractable/refractory epilepsy – both of the following (i and ii):
       i. 40 mg per day ii. 2 tablets per day, 16 mL per day, or 2 films per day; b. Dravet syndrome: 2 mg/kg per day. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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 – Page 3 of 8

    CLINICAL POLICY Clobazam CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration LGS: Lennox-Gastaut syndrome 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 Anticonvulsants-benzodiazepines clonazepam (Klonopin®)
    diazepam rectal gel (Diastat®) Carbamates felbamate (Felbatol®) See full prescribing information See full prescribing information See full prescribing information See full prescribing information GABA modulators vigabatrin (Sabril®)
    tiagabine (Gabitril®) Hydantoins Peganone® (ethotoin) phenytoin (Dilantin®) Succinimides ethosuximide (Zarontin®) Celontin® (methsuximide) Valproic acid divalproex sodium (Depakote®)
    valproic acid (Depakene®) AMPA glutamate receptor antagonists Fycompa® (perampanel) See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information See full prescribing information Anticonvulsants-miscellaneous Briviact® [brivaracetam], carbamazepine [Tegretol®, Tegretol XL®], Aptiom® [eslicarbazepine], Potiga® [ezogabine], gabapentin [Neurontin®], Vimpat® [lacosamide], lamotrigine [Lamictal®], levetiracetam [Keppra®, Spritam®], Page 4 of 8

    CLINICAL POLICY Clobazam Drug Name Dosing Regimen Dose Limit/ Maximum Dose oxcarbazepine [Oxtellar XR®, Trileptal®], Lyrica® [pregabalin], primidone [Mysoline®], Banzel® [rufinamide], topiramate [Topamax®, Qudexy XR®, Trokendi XR®], zonisamide [Zonegran®]) 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): history of hypersensitivity to the drug or its ingredients • Boxed warning(s): risks from concomitant use with opioids; abuse, misuse, and addiction; dependence and withdrawal reactions Appendix D: States with Limitations against Redirections in Certain Settings State Step Therapy Notes Prohibited? No NV Applies to Medicaid requests only • LGS: Failure of ONE of the following, unless clinically significant adverse effects are experienced or all are contraindicated: generic clobazam tablets, generic clobazam oral suspension, alternative drug for LGS (e.g., clonazepam, valproic acid (divalproex), lamotrigine, topiramate, felbamate). • Intractable/refractory epilepsy: Failure of ONE of the following, unless clinically significant adverse effects are experienced or all are contraindicated: generic clobazam tablets, generic clobazam oral suspension, alternative anti- seizure drug (see Appendix B) V. Dosage and Administration
    Indication LGS Maximum Dose ≤ 30 kg body weight: 20 mg/day

    30 kg body weight: 40 mg/day Dosing Regimen Patients ≤ 30 kg body weight: initiate at 5 mg PO daily and titrate as tolerated up to 20 mg daily
    Patients > 30 kg body weight: initiate at 10 mg PO daily and titrate as tolerated up to 40 mg daily A daily dose greater than 5 mg should be administered in divided doses twice daily; a 5 mg daily dose can be administered as a single dose. Page 5 of 8

    CLINICAL POLICY Clobazam Indication Intractable/refractory epilepsy (off-label) Dravet syndrome (off-label) VI. Product Availability
    Drug Name Clobazam (Onfi) Clobazam (Sympazan) Dosing Regimen See LGS Initial: 0.2-0.3 mg/kg/day PO Maximum: 0.5-2 mg/kg/day PO Maximum Dose See LGS See regimen Availability Tablet with a functional score: 10 mg, 20 mg Oral suspension: 2.5 mg/mL in 120 mL bottles Oral film: 5 mg, 10 mg, 20 mg VII.