SEROQUEL XR, Quetiapine Fumarate Form

Quetiapine extended-release (Seroquel XR®) is an atypical antipsychotic. FDA Approved Indication(s) Seroquel XR is indicated for the treatment of: • Schizophrenia in adults and adolescents (13-17 years) • Bipolar I disorder, manic or mixed episodes, in adults and children/adolescents (10-17 years) • Bipolar disorder, depressive episodes, in adults • Major depressive disorder (MDD), as adjunctive therapy with antidepressants, 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 Seroquel XR is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Schizophrenia (must meet all):

1. Diagnosis of schizophrenia;
2. Age ≥ 13 years;

3. 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 quetiapine immediate-release (IR) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;

   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. For Seroquel XR requests, member must use generic quetiapine extended-release (ER), unless contraindicated or clinically significant adverse effects are experienced;
   5. Dose does not exceed both of the following (a and b):
      a. 800 mg per day;
      b. 2 tablets per day. Approval duration: Page 1 of 11

   CLINICAL POLICY Quetiapine Extended-Release Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Bipolar Disorder (must meet all):

4. Diagnosis of bipolar disorder;
5. Age ≥ 10 years;
6. 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 quetiapine IR at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
   
   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. For Seroquel XR requests, member must use generic quetiapine ER, unless contraindicated or clinically significant adverse effects are experienced;
   5. Dose does not exceed one of the following (a or b):
      a. Adults (i and ii) i. 800 mg per day;
      ii. 2 tablets per day;
      b. Children and adolescents (i and ii):
      i. 600 mg per day;
      ii. 2 tablets per day.
      Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less C. Major Depressive Disorder (must meet all):
   6. Diagnosis of MDD;
7. Age ≥ 18 years;
8. 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. For all other requests, both of the following (i and ii): i. 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; ii. 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;

9. Seroquel XR is prescribed concurrently with an antidepressant; Page 2 of 11

   CLINICAL POLICY Quetiapine Extended-Release

   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 mental health settings (see Appendix D); b. For Seroquel XR requests, member must use generic quetiapine ER, unless contraindicated or clinically significant adverse effects are experienced;
   6. Dose does not exceed both of the following (a and b):
      a. 300 mg per day;
      b. 2 tablets 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):
   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 Seroquel XR for schizophrenia or bipolar disorder 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);
10. Member is responding positively to therapy;

11. For Seroquel XR requests, member must use generic quetiapine ER, unless contraindicated or clinically significant adverse effects are experienced;
    Page 3 of 11

    CLINICAL POLICY Quetiapine Extended-Release

    4. If request is for a dose increase, new dose does not exceed any of the following (a, b, or c): a. Schizophrenia (i and ii):
       i. 800 mg per day;
       ii. 2 tablets per day; b. Bipolar disorder, one of the following (i or ii): i. Adults (1 and 2):
       1) 800 mg per day;
       2) 2 tablets per day; ii. Children and adolescents (1 and 2):
       1) 600 mg per day;
       2) 2 tablets per day;
       c. MDD (i and ii):
       i. 300 mg per day;
       ii. 2 tablets 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):
    5. 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
    6. 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. Page 4 of 11

    CLINICAL POLICY Quetiapine Extended-Release IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration ER: extended-release IR: immediate-release MDD: major depressive disorder SNRI: serotonin/norepinephrine reuptake inhibitor SSRI: selective serotonin reuptake inhibitor TCA: tricyclic antidepressant XR: extended-release 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 quetiapine immediate-release (Seroquel®) Schizophrenia Initial: 25 mg PO BID; target: 400 to 800 mg/day 800 mg/day Bipolar Disorder Initial: 50 mg PO BID; target: 400 to 800 mg/day Selective Serotonin Reuptake Inhibitors (SSRIs) citalopram (Celexa®) escitalopram (Lexapro®) fluoxetine (Prozac®) Major Depressive Disorder Refer to prescribing information fluvoxamine*
    (immediate-release) (Luvox®) paroxetine (Paxil®, Paxil CR®) sertraline (Zoloft®) 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) Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) desvenlafaxine (Pristiq®) duloxetine (Cymbalta®) Major Depressive Disorder Refer to prescribing information 400 mg/day 120 mg/day Page 5 of 11

    CLINICAL POLICY Quetiapine Extended-Release Drug Name Dosing Regimen Fetzima® (levomilnacipran)
    venlafaxine (Effexor®, Effexor XR®) Tricyclic Antidepressant (TCAs) amitriptyline (Elavil®) amoxapine clomipramine* (Anafranil®) desipramine (Norpramin®) doxepin imipramine HCl imipramine pamoate nortriptyline (Pamelor®) protriptyline trimipramine Major Depressive Disorder Refer to prescribing information Monoamine Oxidase Inhibitors Marplan® (isocarboxazid) phenelzine (Nardil®) selegiline (EMSAM® transdermal; Eldepryl®, Zelapar®) tranylcypromine (Parnate®) Other Antidepressants bupropion (Aplenzin®, Forfivo XL®, Wellbutrin®, Wellbutrin SR®, Wellbutrin XL®) Major Depressive Disorder Refer to prescribing information Major Depressive Disorder Refer to prescribing information Dose Limit/ Maximum Dose 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 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 Page 6 of 11

    CLINICAL POLICY Quetiapine Extended-Release Drug Name Dosing Regimen mirtazapine (Remeron®) perphenazine/ amitriptyline nefazodone trazodone (Oleptro®) Dose Limit/ Maximum Dose Extended-release (HBr): 522 mg/day 45 mg/day 16 mg/day perphenazine and 200 mg/day amitriptyline 600 mg/day Immediate-release: 400 mg/day Extended-release: 375 mg/day 20 mg/day 40 mg/day Trintellix® (vortioxetine) 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 Seroquel XR or any components in the formulation • Boxed warning(s): increased mortality in elderly patients with dementia-related psychosis; and suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants.
    Appendix D: States with Limitations against Redirections in Certain Mental Health Settings State Step Therapy Notes Prohibited? Yes AR NV No Applies to HIM requests only For the treatment of psychosis and serious mental illness through antipsychotic prescription drugs, no step therapies allowed. Note: For Seroquel XR requests, member must use generic quetiapine extended-release (ER), unless contraindicated or clinically significant adverse effects are experienced Applies to Medicaid requests only • Schizophrenia/bipolar disorder: Failure of generic quetiapine extended-release (ER) or quetiapine immediate-release (IR), unless clinically significant adverse effects are experienced or both are contraindicated. • MDD: Failure of one of the following 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: generic Page 7 of 11

    CLINICAL POLICY Quetiapine Extended-Release State Step Therapy Notes Prohibited? TX No quetiapine ER, aripiprazole, or an antidepressant (e.g., selective serotonin reuptake inhibitor [SSRI], serotonin- norepinephrine reuptake inhibitor [SNRI], tricyclic antidepressant [TCA], bupropion, mirtazapine). Applies to HIM requests only For MDD ONLY: 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, 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. Note: For Seroquel XR requests, member must use generic quetiapine extended-release (ER), unless contraindicated or clinically significant adverse effects are experienced V. Dosage and Administration
    Indication Schizophrenia
    Bipolar I disorder
    MDD Dosing Regimen Adults: Initial: 300 mg PO QD Target: 400 to 800 mg/day Adolescents: Initial: 50 mg PO QD Target: 400 to 800 mg/day Manic or mixed episodes Adults: Initial: 300 mg PO QD Target: 400 to 800 mg/day Children and adolescents Initial: 50 mg PO QD Target: 400 to 600 mg/day Depressive episodes Adults: Initial: 50 mg PO QD Target: 300 mg/day Adults: Initial: 50 mg PO QD Target: 150 to 300 mg/day Page 8 of 11 Maximum Dose 800 mg/day Manic or mixed episodes Adults: 800 mg/day Children and adolescents: 600 mg/day Depressive episodes 300 mg/day 300 mg/day

    CLINICAL POLICY Quetiapine Extended-Release VI. Product Availability
    Extended-release tablets: 50 mg, 150 mg, 200 mg, 300 mg, 400 mg VII.