Sunflower Health PlanCommercial Clinical Policy

REXULTI, Brexpiprazole Form


REXULTI (Brexpiprazole) for Major Depressive Disorder

Indications

(300902) Is the diagnosis major depressive disorder? 
(300903) Is the patient's age greater than or equal to 18 years? 
(300904) Is the request from a state with step therapy limitations in certain mental health settings as listed in Appendix D, or has the patient failed three antidepressants from at least two different classes each used for four weeks or more, unless clinically significant adverse effects were experienced or there is an age contraindication? 
(300905) Has the patient failed a four-week trial of aripiprazole at up to maximally indicated doses when used concurrently with an antidepressant, unless contraindicated or if clinically significant adverse effects are experienced? 
(300906) Will REXULTI be prescribed concurrently with an antidepressant? 

YesNoN/A
YesNoN/A
YesNoN/A

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Effective Date

12/01/2015

Last Reviewed

08/23

Original Document

  Reference



Brexpiprazole (Rexulti®) is an atypical antipsychotic.
FDA Approved Indication(s) Rexulti is indicated for the: • Adjunctive treatment of major depressive disorder (MDD) in adults
• Treatment of schizophrenia in adults and pediatric patients ages 13 years and older • Treatment of agitation associated with dementia due to Alzheimer’s disease (AD) Limitation of use: Rexulti is not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to AD. 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 Rexulti is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Major Depressive Disorder (must meet all):

  1. Diagnosis of MDD;
    1. Age ≥ 18 years;
    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 mental health settings (see Appendix D); b. Failure of THREE antidepressants from at least TWO different classes (e.g., selective serotonin reuptake inhibitor [SSRI], serotonin-norepinephrine reuptake inhibitor [SNRI], tricyclic antidepressant [TCA], bupropion, mirtazapine) at up to maximally indicated doses, each used for ≥ 4 weeks, unless member is unable to satisfy this requirement due to clinically significant adverse effects experienced, member’s age ≥ 65 years, or contraindication(s) to multiple antidepressants;

  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 mental health settings (see Appendix D); Page 1 of 11

    CLINICAL POLICY Brexpiprazole b. Failure of a ≥ 4-week trial of aripiprazole at up to maximally indicated doses, used concurrently with an antidepressant, unless contraindicated or clinically significant adverse effects are experienced;

  3. Rexulti is prescribed concurrently with an antidepressant;
    1. Dose does not exceed both of the following (a and b):
      a. 3 mg per day; b. 1 tablet per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Schizophrenia (must meet all):
    2. Diagnosis of schizophrenia;
    3. Age ≥ 13 years;
    4. Member meets one of the following (a, b, or c): a. Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D); b. Failure of two of the following generic atypical antipsychotics at up to maximally indicated doses, each used for ≥ 4 weeks, unless clinically significant adverse effects are experienced or all are contraindicated: risperidone, quetiapine, olanzapine, ziprasidone; c. Member has diabetes mellitus or body mass index (BMI) > 30 kg/m2;
  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 mental health settings (see Appendix D); b. Failure of a ≥ 4-week trial of aripiprazole at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
  5. Dose does not exceed both of the following (a and b):
    a. 4 mg per day; b. 1 tablet per day. Approval duration:
    Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less C. Alzheimer’s Disease Related Agitation

  6. Diagnosis of agitation associated with dementia due to AD;

    1. Age ≥ 18 years;
    2. Rexulti is not prescribed as an as needed (“prn”) treatment;
    3. Dose does not exceed both of the following (a and b):
      a. 3 mg per day;
      b. 1 tablet per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less Page 2 of 11

    CLINICAL POLICY Brexpiprazole D. 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. 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. Documentation supports that member is currently receiving Rexulti for schizophrenia and has received this medication for at least 30 days; c. 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);
    1. Member is responding positively to therapy;
    2. If request is for a dose increase, new dose does not exceed (a or b): a. MDD or AD related agitation (i and ii):
      i. 3 mg per day; ii. 1 tablet per day; b. Schizophrenia (i and ii):
      i. 4 mg per day; ii. 1 tablet 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):

  10. 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 3 of 11

    CLINICAL POLICY Brexpiprazole 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

  11. 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 AD: Alzheimer’s disease BMI: body mass index CrCl: creatinine clearance CYP: cytochrome P450
    FDA: Food and Drug Administration MDD: major depressive disorder SNRI: serotonin-norepinephrine reuptake inhibitors SSRI: selective serotonin reuptake inhibitors TCA: tricyclic antidepressants
    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 Antipsychotics aripiprazole (Abilify) olanzapine (Zyprexa®) Schizophrenia Adults: 10 to 15 mg PO QD Major Depressive Disorder 5 to 10 mg PO QD Schizophrenia Initial: 5 to 10 mg PO QD; target: 10 mg PO QD Schizophrenia: 30 mg/day Major Depressive Disorder: 15 mg/day 20 mg/day Page 4 of 11

    CLINICAL POLICY Brexpiprazole Drug Name Dosing Regimen quetiapine immediate-release (Seroquel®) risperidone (Risperdal®) ziprasidone (Geodon®) Schizophrenia Initial: 25 mg PO BID; target: 400 to 800 mg/day Schizophrenia Initial: 1 mg PO BID or 2 mg PO QD; target: 4 to 8 mg PO QD Schizophrenia 20 mg PO BID Selective Serotonin Reuptake Inhibitors (SSRIs) citalopram (Celexa®) escitalopram (Lexapro®) fluoxetine (Prozac®) fluvoxamine
    (immediate-release) (Luvox®) paroxetine (Paxil®, Paxil CR®, Pexeva®) Major Depressive Disorder Refer to prescribing information sertraline (Zoloft®) Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) desvenlafaxine (Pristiq®) duloxetine (Cymbalta®) Fetzima® (levomilnacipran)
    venlafaxine (Effexor®, Effexor XR®) Tricyclic Antidepressant (TCAs) amitriptyline (Elavil®) amoxapine Major Depressive Disorder Refer to prescribing information clomipramine     (Anafranil®) desipramine (Norpramin®) doxepin (Sinequan®) Major Depressive Disorder Refer to prescribing information Dose Limit/ Maximum Dose 800 mg/day Schizophrenia Adolescents: 6 mg/day Adults: 16 mg/day 160 mg/day 40 mg/day 20 mg/day Immediate-release: 80 mg/day (20 mg/day if pediatric) Delayed-release: 90 mg/week 150 mg/day Immediate-release: 50 mg/day (40 mg/day if geriatric) Extended-release: 62.5 mg/day (50 mg/day if geriatric) 200 mg/day (20 mg/day if age 6-11 years*) 400 mg/day 120 mg/day 120 mg/day Extended-release: 225 mg/day 150 mg/day 400 mg/day (300 mg/day if geriatric) 250 mg/day (200 mg/day if pediatric) 300 mg/day (100 mg/day if pediatric) 300 mg/day Page 5 of 11

    CLINICAL POLICY Brexpiprazole Drug Name Dosing Regimen imipramine HCl (Tofranil®) imipramine pamoate (Tofranil PM®) nortriptyline (Pamelor®) protriptyline (Vivactil®) trimipramine (Surmontil®) Monoamine Oxidase Inhibitors isocarboxazid (Marplan®) phenelzine (Nardil®) selegiline (EMSAM® transdermal; Eldepryl®, Zelapar®, Carbex®) tranylcypromine (Parnate®) Other Antidepressants bupropion (Aplenzin®, Budeprion SR® , Budeprion XL®, Forfivo XL®, Wellbutrin®, Wellbutrin SR®, Wellbutrin XL®) Major Depressive Disorder Refer to prescribing information mirtazapine (Remeron®) perphenazine/ amitriptyline (Triavil®) maprotiline (Ludiomil®) nefazodone (Serzone®) trazodone (Desyrel®, Oleptro®) Major Depressive Disorder Refer to prescribing information Dose Limit/ Maximum Dose 200 mg/day (150 mg/day if geriatric or pediatric) 200 mg/day (100 mg/day if geriatric or pediatric) 150 mg/day 60 mg/day (30 mg/day if geriatric or pediatric) 200 mg/day (100 mg/day if geriatric or pediatric) 60 mg/day 90 mg/day Transdermal: 12 mg/24 hr Oral*: 30 mg/day 60 mg/day Immediate-release: 450 mg/day (300 mg/day if pediatric) Sustained-release: 400 mg/day Extended-release (HCl): 450 mg/day Extended-release (HBr): 522 mg/day 45 mg/day 16 mg/day perphenazine and 200 mg/day amitriptyline 150 mg/day 600 mg/day Immediate-release: 400 mg/day Extended-release: 375 mg/day 20 mg/day 40 mg/day vortioxetine (Trintellix®) vilazodone (Viibryd®) 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 Rexulti or any of its components Page 6 of 11

    CLINICAL POLICY Brexpiprazole • Boxed warning(s):
    o Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. Rexulti is not approved for the treatment of patients with dementia-related psychosis. o Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behaviors.
    Appendix D: States with Limitations against Redirections in Certain Mental Health Settings State Step Therapy Notes Prohibited? Yes AR NV No TX No Applies to HIM requests only For the treatment of psychosis and serious mental illness through antipsychotic prescription drugs, no step therapies allowed. Applies to Medicaid requests only • MDD: Failure of aripiprazole or an antidepressant (e.g., selective serotonin reuptake inhibitor [SSRI], serotonin- norepinephrine reuptake inhibitor [SNRI], tricyclic antidepressant [TCA], bupropion, mirtazapine) at up to maximally indicated doses, used for ≥ 4 weeks, unless member is unable to satisfy this requirement due to clinically significant adverse effects experienced, member’s age ≥ 65 years, or contraindication(s) to multiple antidepressants. • Schizophrenia: Failure of ONE of the following at up to maximally indicated doses, each used for ≥ 4 weeks, unless clinically significant adverse effects are experienced or all are contraindicated: aripiprazole, risperidone, quetiapine, olanzapine, ziprasidone Applies to HIM requests only • MDD: Failure of aripiprazole or an antidepressant (e.g., selective serotonin reuptake inhibitor [SSRI], serotonin- norepinephrine reuptake inhibitor [SNRI], tricyclic antidepressant [TCA], bupropion, mirtazapine) at up to maximally indicated doses, used for ≥ 4 weeks, unless member is unable to satisfy this requirement due to clinically significant adverse effects experienced, member’s age ≥ 65 years, or contraindication(s) to multiple antidepressants. • Schizophrenia: Failure of ONE of the following at up to maximally indicated doses, each used for ≥ 4 weeks, unless clinically significant adverse effects are experienced or all are contraindicated: aripiprazole, risperidone, quetiapine, olanzapine, ziprasidone Page 7 of 11

    CLINICAL POLICY Brexpiprazole V. Dosage and Administration
    Indication Adjunctive treatment of MDD Schizophrenia Dosing Regimen 0.5 mg or 1 mg PO QD, up to target dosage of 2 mg once daily Adults: 1 mg PO QD, up to target dosage of 2 mg to 4 mg once daily
    Maximum Dose 3 mg/day
    4 mg/day
    Agitation associated with dementia due to AD • Moderate to severe hepatic impairment (Child-Pugh score ≥ 7): Maximum recommended dosage is 2 mg 3 mg/day Pediatric (13-17 years): 0.5 mg PO QD, up to target dosage of 2 mg to 4 mg once daily
    0.5 mg PO QD, up to target dosage of 2 mg once daily once daily for patients with MDD and 3 mg once daily for patients with schizophrenia
    • Moderate, severe or end-stage renal impairment [creatinine clearance (CrCl) < 60 mL/minute): Maximum recommended dosage is 2 mg once daily for patients with MDD and 3 mg once daily for patients with schizophrenia
    • Known cytochrome P450 (CYP) 2D6 Poor Metabolizers: Reduce the usual dosage by half
    VI. Product Availability
    Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg
    VII.