Paliperidone Long-Acting Injections (Invega Hafyera, Invega Sustenna, Invega Trinza) Form

Paliperidone (Invega Hafyera™, Invega Sustenna®, Invega Trinza®) is an atypical antipsychotic. FDA Approved Indication(s) Invega Hafyera is indicated for the treatment of schizophrenia in adults after they have been adequately treated with: • A once-a-month paliperidone palmitate extended-release injectable suspension (e.g., Invega Sustenna) for at least four months or; • An every-three-month paliperidone palmitate extended-release injectable suspension (e.g., Invega Trinza) for at least one three-month cycle. Invega Sustenna is indicated: • For the treatment of schizophrenia in adults. • For the treatment of schizoaffective disorder in adults as monotherapy and as an adjunct to mood stabilizers or antidepressants. Invega Trinza is indicated for the treatment of schizophrenia in patients after they have been adequately treated with Invega Sustenna (1-month paliperidone palmitate extended-release injectable suspension) for at least four months. 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 Invega Hafyera, Invega Sustenna, and Invega Trinza 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. The requested product was initiated in an inpatient setting during a recent (within 60 days) hospital admission;
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   CLINICAL POLICY Paliperidone Long-Acting Injections b. History of non-adherence to oral antipsychotic therapy (see Appendix D for examples), and one of the following (i, ii, or iii): i. If Invega Trinza is requested, adequate treatment has been established with Invega Sustenna for at least the last 4 months; ii. If Invega Sustenna is requested, both of the following (a and b): a) Established tolerability with oral paliperidone or oral risperidone; b) No known hypersensitivity to paliperidone or risperidone; iii. If Invega Hafyera is requested, one of the following (a or b): a) Adequate treatment has been established with Invega Sustenna for at least the last 4 months; b) Adequate treatment has been established with Invega Trinza for at least one three-month cycle;

   5. Dose does not exceed any of the following (a, b, or c): a. Invega Hafyera: 1,560 mg every 6 months; b. Invega Sustenna: 234 mg per month; c. Invega Trinza: 819 mg every 3 months. Approval duration: 6 months
      B. Schizoaffective Disorder (must meet all):
5. Diagnosis of schizoaffective disorder;
6. Request is for Invega Sustenna;
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 (preferred agent) or paliperidone;
   b. Therapy was initiated in an inpatient setting during a recent (within 60 days) hospital admission;

   6. Dose does not exceed 234 mg per month. 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 Page 2 of 9

   CLINICAL POLICY Paliperidone Long-Acting Injections 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):

   1. Member meets one of the following (a, b, or c): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B) c. Therapy was initiated in an inpatient setting for a covered indication during a recent (within 60 days) hospital admission;
   2. 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. Invega Hafyera: 1,560 mg every 6 months; b. Invega Sustenna: 234 mg per month; c. Invega Trinza: 819 mg every 3 months. Approval duration: 12 months
    B. Other diagnoses/indications (must meet 1 or 2):

    1. If his 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.
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    CLINICAL POLICY Paliperidone Long-Acting Injections 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 12 mg/day 16 mg/day paliperidone (Invega) risperidone (Risperdal) Schizophrenia and schizoaffective disorder Adults: initially, 6 mg PO QD Recommended dose: 3-12 mg/day 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 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): known hypersensitivity to paliperidone, risperidone, or to any excipients. • Boxed warning(s): increased risk of death in elderly patients with dementia-related psychosis treated with antipsychotic drugs. Atypical/Second Generation Antipsychotics 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) 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)
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    CLINICAL POLICY Paliperidone Long-Acting Injections †Most typical/first generation antipsychotics are available only as generics in the U.S. Long-acting injectable formulation available
    V. Dosage and Administration
    Indication Schizophrenia Drug Name Paliperidone (Invega Hafyera) Schizophrenia Paliperidone (Invega Sustenna) Maximum Dose 1,560 mg every 6 months 234 mg/month Dosing Regimen Invega Hafyera is to be used only after Invega Sustenna has been established as adequate treatment for at least four months or after Invega Trinza has been established as adequate treatment for at least one three-month cycle. The recommended initial Invega Hafyera dose is based on the previous dose of either Invega Sustenna or Invega Trinza, and is initiated when the next Invega Sustenna or Invega Trinza dose would have been scheduled. Last Invega Sustenna dose: Invega Hafyera dose to initiate 156 mg: 1,092 mg 234 mg: 1,560 mg There are no equivalent doses of Invega Hafyera for the 39 mg, 78 mg, or 117 mg doses of Invega Sustenna, which were not studied. Last Invega Trinza dose: Invega Hafyera dose to initiate* 546 mg: 1,092 mg 819 mg: 1,560 mg *There are no equivalent doses of Invega Hafyera for the 273 mg or 410 mg, or 117 mg doses of Invega Trinza, which were not studied. Following the initial dose, Invega Hafyera should be administered IM every 6 months.
    Initial: 234 mg IM on day 1 and 156 mg one week later (day 8), both administered in the deltoid muscle Maintenance: 39-234 mg IM monthly in either the deltoid or gluteal muscle Page 5 of 9

    CLINICAL POLICY Paliperidone Long-Acting Injections Drug Name Indication Schizoaffective disorder Schizophrenia Paliperidone (Invega Trinza) Maximum Dose 234 mg/month 819 mg every 3 months Dosing Regimen Initial: 234 mg IM on day 1 and 156 mg one week later (day 8), both administered in the deltoid muscle Maintenance: 78-234 mg IM monthly in either the deltoid or gluteal muscle Invega Trinza is to be used only after Invega Sustenna® (1-month paliperidone palmitate extended- release injectable suspension) has been established as adequate treatment for at least four months.
    Initiate Invega Trinza when the next 1-month paliperidone palmitate dose is scheduled with an Invega Trinza dose based on the previous 1-month injection dose, using the equivalent 3.5-fold higher dose as shown:
    Last Invega Sustenna dose: Invega Trinza dose to initiate 78 mg: 273 mg 117 mg: 410 mg 156 mg: 546 mg 234 mg: 819 mg Following the initial Invega dose, Invega Trinza should be administered IM every 3 months. Invega Trinza may be administered up to 7 days before or after the monthly time point of the next scheduled paliperidone palmitate 1-month dose. Administered 5 weeks after the first injection VI. Product Availability
    Drug Name Paliperidone (Invega Hafyera) Paliperidone (Invega Sustenna) Availability Extended-release injectable suspension: 1,092 mg/3.5 mL, 1,560 mg/5 mL Extended-release injectable suspension: 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, 156 mg/1 mL, or 234 mg/1.5 mL Paliperidone (Invega Trinza) Extended-release injectable suspension: 273 mg/0.875 mL, 410 mg/1.315 mL, 546 mg/1.75 mL, or 819 mg/2.625 mL Page 6 of 9

    CLINICAL POLICY Paliperidone Long-Acting Injections VII.