RISPERDAL CONSTA, Risperidone Microspheres PERSERIS, Risperidone Form

Risperidone (Perseris®, Risperdal Consta®, Rykindo®, Uzedy™) is an atypical antipsychotic. FDA Approved Indication(s) Risperdal Consta and Rykindo are indicated: • For the treatment of schizophrenia. Rykindo is specifically indicated in adults. • For the maintenance treatment of bipolar I disorder as monotherapy or as adjunctive therapy to lithium or valproate. Rykindo is specifically indicated in adults. Perseris and Uzedy are indicated for the treatment of schizophrenia in adults. 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 Perseris, Risperdal Consta, Rykindo, and Uzedy are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Schizophrenia (must meet all):

1. Diagnosis of schizophrenia;
2. Prescribed by or in consultation with a psychiatrist;
3. Age ≥ 18 years;

4. Member meets one of the following (a or b):
   a. History of non-adherence to oral antipsychotic therapy (see Appendix D for examples) and has established tolerability to oral risperidone;
   b. Therapy was initiated in an inpatient setting during a recent (within 60 days) hospital admission;

   5. Dose does not exceed any of the following (a, b, or c): a. Perseris: 120 mg every month; b. Risperdal Consta or Rykindo: 50 mg every 2 weeks;
      c. Uzedy (i or ii): i. 125 mg every month;
      ii. 250 mg every 2 months. Approval duration: 6 months
      Page 1 of 8

   CLINICAL POLICY Risperidone Long-Acting Injection B. Bipolar Disorder (must meet all):

5. Diagnosis of bipolar disorder;
6. Request is for Risperdal Consta or Rykindo;
7. Prescribed by or in consultation with a psychiatrist;
8. Age ≥ 18 years;
9. Member meets one of the following (a or b):
   a. History of non-adherence to oral antipsychotic therapy (see Appendix D for examples) and has established tolerability to oral risperidone;
   b. Therapy was initiated in an inpatient setting during a recent (within 60 days) hospital admission;
   
   6. Dose does not exceed 50 mg every 2 weeks. Approval duration: 6 months
      C. Other diagnoses/indications (must meet 1 or 2):
   7. 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
   8. 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):
   9. Currently receiving medication via Centene benefit, or documentation supports one of the following (a or b): a. Member is currently receiving Perseris, Risperdal Consta, Rykindo, or Uzedy for schizophrenia or bipolar disorder and has received this medication for at least 30 days; b. Therapy was initiated in an inpatient setting, for a covered indication, during a recent (within 60 days) hospital admission;
   10. Member is responding positively to therapy;

10. If request is for a dose increase, new dose does not exceed any of the following (a, b, or c): a. Perseris: 120 mg every month; b. Risperdal Consta or Rykindo: 50 mg every 2 weeks; Page 2 of 8

    CLINICAL POLICY Risperidone Long-Acting Injection c. Uzedy (i or ii):
    i. 125 mg every month;
    ii. 250 mg every 2 months. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

    1. 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
    2. 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; B. Dementia-related psychosis.
       IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key 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 Schizophrenia: 16 mg/day Bipolar disorder: 6 mg/day risperidone (Risperdal) Schizophrenia Adults: initially, 2 mg/day PO (as a single dose) or 1 mg PO BID; adjust as tolerated to the recommended target dose of 4 to 8 mg/day Effective dose range: 4 to 16 mg/day Page 3 of 8

    CLINICAL POLICY Risperidone Long-Acting Injection Drug Name Dosing Regimen Dose Limit/ Maximum Dose Bipolar Disorder Adults: initially, 2-3 mg PO QD Effective dose range: 1 to 6 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): hypersensitivity to risperidone, paliperidone, or to any excipients • Boxed warning(s): increased mortality in elderly patients with dementia-related psychosis Appendix D: Examples of Oral Antipsychotics – Generic (Brand) Typical/First Generation Antipsychotics† Chlorpromazine (Thorazine) Fluphenazine (Prolixin) Haloperidol (Haldol) Loxapine (Loxitane) Perphenazine (Trilafon) Pimozide (Orap) Thioridazine (Mellaril) Thiothixene (Navane) Trifluoperazine (Stelazine) Atypical/Second Generation Antipsychotics Aripiprazole (Abilify) Asenapine maleate (Saphris) Brexpiprazole (Rexulti) Cariprazine (Vraylar) Clozapine (Clozaril) Iloperidone (Fanapt)
    Lumateperone (Caplyta) Lurasidone (Latuda) Olanzapine (Zyprexa) Olanzapine/Fluoxetine (Symbyax) Paliperidone (Invega) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon)
    †Most typical/first generation antipsychotics are available only as generics in the U.S. *Long-acting injectable formulation available V. Dosage and Administration
    Indication Bipolar disorder, Schizophrenia Drug Name Risperidone (Risperdal Consta, Rykindo) Risperidone (Perseris) Risperidone (Uzedy) Schizophrenia Schizophrenia Dosing Regimen 25 mg IM every 2 weeks. Some patients not responding to 25 mg may benefit from a higher dose of 37.5 mg or 50 mg 90 mg or 120 mg SC once monthly Uzedy SC once monthly (50 mg, 75 mg, 100 mg, or 125 mg) or once every 2 months Maximum Dose 50 mg/2 weeks 120 mg/month 125 mg/month or 250 mg/2 months Page 4 of 8

    CLINICAL POLICY Risperidone Long-Acting Injection Drug Name Indication VI. Product Availability
    Maximum Dose Dosing Regimen (100 mg, 150 mg, 200 mg, or 250 mg) starting the day after the last dose of oral therapy. See Prescribing Information for dosage recommendations for switching from oral risperidone to Uzedy. Neither a loading dose or supplemental oral risperidone doses are recommended while switching. Patients can switch between doses of Uzedy once monthly and once every 2 months by administering the first dose of the new dosing regimen on the next scheduled date of administration in the original dosing regimen Drug Name Availability Risperidone (Risperdal Consta) Vial kits: 12.5 mg, 25 mg, 37.5 mg, and 50 mg Risperidone (Perseris) Risperidone (Rykindo) Extended-release injectable suspension: 90 mg, 120 mg Extended-release injectable suspension: 12.5 mg, 25 mg, 37.5 mg, and 50 mg Extended-release injectable suspension (single-dose prefilled syringes): 50 mg/0.14 mL, 75 mg/0.21 mL, 100 mg/0.28 mL, 125 mg/0.35 mL, 150 mg/0.42 mL, 200 mg/0.56 mL, and 250 mg/0.7 mL Risperidone (Uzedy) VII.