ARISTADA, Aripiprazole Lauroxil ABILIFY MAINTENA, Aripiprazole ARISTADA INITIO, Aripiprazole Lauroxil Form

Aripiprazole monohydrate (Abilify Maintena®, Abilify Asimtufii®) and aripiprazole lauroxil (Aristada®, Aristada Initio®) are atypical antipsychotics. FDA Approved Indication(s) Abilify Maintena and Abilify Asimtufii are indicated:
• For the treatment of schizophrenia in adults • For maintenance monotherapy treatment of bipolar I disorder in adults Aristada is indicated:
• For the treatment of schizophrenia in adults Aristada Initio, in combination with oral aripiprazole, is indicated: • For the initiation of Aristada when used 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 Abilify Maintena, Abilify Asimtufii, Aristada, and Aristada Initio 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 aripiprazole;
   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, c, or d): a. Abilify Maintena: 400 mg per month; b. Abilify Asimtufii: 960 mg per 2 months; Page 1 of 9

   CLINICAL POLICY Aripiprazole Long-Acting Injections c. Aristada (i, ii, or iii):
   i. 882 mg per month; ii. 882 mg per 6 weeks;
   iii. 1,064 mg per 2 months; d. Aristada Initio: 675 mg one-time dose (used in conjunction with Aristada and an oral one-time 30 mg dose of aripiprazole). Approval duration: 6 months
   B. Bipolar Disorder (must meet all):

5. Diagnosis of bipolar disorder;
6. Request is for Abilify Maintena or Abilify Asimtufii;
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 aripiprazole;
   b. Therapy was initiated in an inpatient setting during a recent (within 60 days) hospital admission;
   
   6. Dose does not exceed any of the following (a or b):
      a. Abilify Maintena: 400 mg per month; b. Abilify Asimtufii: 960 mg per 2 months.
      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 (health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: 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: 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. Currently receiving medication via Centene benefit, or documentation supports one of the following (a or b): a. Member is currently receiving Abilify Maintena, Abilify Asimtufii, or Aristada for bipolar disorder or schizophrenia and has received this medication for at least 30 days; Page 2 of 9

    CLINICAL POLICY Aripiprazole Long-Acting Injections b. 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;
11. If request is for a dose increase, new dose does not exceed any of the following (a, b, or c): a. Abilify Maintena: 400 mg per month; b. Abilify Asimtufii: 960 mg per 2 months; c. Aristada (i, ii, or iii):
    i. 882 mg per month;
    ii. 882 mg per 6 weeks;
    iii. 1,064 mg per 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 (health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

12. 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: 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.PMN.53 for Medicaid and HIM.PA.154 for health insurance marketplace, 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. Page 3 of 9

    CLINICAL POLICY Aripiprazole Long-Acting Injections Drug Name Dosing Regimen aripiprazole (Abilify) 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. Bipolar Disorder and Schizophrenia Adults: 10-15 mg PO QD Dose Limit/ Maximum Dose 30 mg/day Appendix C: Contraindications / Boxed warnings • Contraindication(s): known hypersensitivity to aripiprazole • 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
    Drug Name Indication Dosing Regimen Aripiprazole monohydrate (Abilify Maintena) Schizophrenia, The recommended starting and maintenance dose is 400 mg IM monthly (no sooner than 26 days after the previous injection). Dose can be reduced to 300 mg in patients with adverse reactions.
    Maximum Dose 400 mg/month Page 4 of 9

    Maximum Dose 960 mg/2 month 882 mg/month CLINICAL POLICY Aripiprazole Long-Acting Injections Drug Name Indication Dosing Regimen bipolar I disorder Aripiprazole monohydrate (Abilify Asimtufii) Schizophrenia, bipolar I disorder Schizophrenia Aripiprazole lauroxil (Aristada) • Used in combination with oral aripiprazole for the first 14 consecutive days. • Known CYP2D6 poor metabolizers: Recommended starting and maintenance dose is 300 mg IM monthly as a single injection. The recommended dose is 960 mg IM once every 2 months (56 days after the previous injection). Dose can be reduced to 720 mg in patients with adverse reactions. • Patients receiving oral antipsychotics: Administer the first dose of Abilify Asimtufii along with oral aripiprazole or another oral antipsychotic (and known to tolerate aripiprazole) for 14 consecutive days.
    • Patients receiving Abilify Maintena: Administer Abilify Asimtufii 960 mg IM (once every 2 months as a single injection) in place of the next scheduled injection of the Abilify Maintena.
    • Known CYP2D6 poor metabolizers: Recommended dose is 720 mg IM once every 2 months as a single injection. Initiation Method 1:
    Administer one IM injection of Aristada Initio 675 mg (deltoid or gluteal muscle) and one dose of oral aripiprazole 30mg in conjunction with the first Aristada injection.
    • First Aristada injection may be started on same day or up to 10 days after administration of Aristada Initio • Avoid injection of both Aristada and Aristada Initio into the same deltoid or gluteal muscle. Page 5 of 9

    CLINICAL POLICY Aripiprazole Long-Acting Injections Drug Name Indication Dosing Regimen Maximum Dose Initiation Method 2:
    Used in combination with oral aripiprazole for the first 21 consecutive days. Depending on individual patient’s needs, treatment can be initiated at a dose of 441 mg, 662 mg, or 882 mg IM administered monthly; 882 mg administered every 6 weeks; or 1064 mg administered every 2 months. Dose adjustments are required for 1) known CYP2D6 poor metabolizers and 2) for patients taking CYP3A4 inhibitors, CYP2D6 inhibitors, or CYP3A4 inducers for more than 2 weeks. Single dose of 675 mg IM injection, in combination with a single dose of 30 mg oral aripiprazole, to initiate Aristada treatment or to re-initiate Aristada treatment. Aristada may be started at the same time or within 10 days of Aristada Initio/oral aripiprazole. 675 mg once Aripiprazole lauroxil (Aristada Initio) Schizophrenia (therapy initiation only) VI. Product Availability
    Drug Name Aripiprazole monohydrate (Abilify Maintena) Aripiprazole monohydrate (Abilify Asimtufii) Aripiprazole lauroxil (Aristada) Aripiprazole lauroxil (Aristada Initio) Availability Extended-release powder for suspension for injection (single- dose pre-filled dual chamber syringes and single-dose vials): 300 mg and 400 mg
    Extended-release injectable suspension (single-dose pre-filled syringes): 720 mg/2.4 mL, 960 mg/3.2 mL Extended-release injectable suspension (single-use pre-filled syringes): 441 mg/1.6 mL, 662 mg/2.4 mL, 882 mg/3.2 mL or 1,064 mg/3.9 mL Extended-release injectable suspension (single-use pre-filled syringe): 675 mg/2.4 mL VII.