FETZIMA, Levomilnacipran HCl Form

Levomilnacipran (Fetzima®) is a serotonin and norepinephrine reuptake inhibitor (SNRI). FDA Approved Indication(s) Fetzima is indicated for the treatment of major depressive disorder in adults. Limitation(s) of use: Fetzima is not approved for the management of fibromyalgia. The efficacy and safety of Fetzima for the management of fibromyalgia have not been established. 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 Fetzima is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Major Depressive Disorder (must meet all):

1. Diagnosis of major depressive disorder;
2. Age ≥ 18 years;

3. 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. Request is for Fidelis Ambetter (New York Exchange): Failure of ONE of the following, tried for ≥ 4 weeks at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated: SSRI, SNRI, bupropion, mirtazapine, vilazodone (generic Viibryd®); c. Failure of TWO of the following, each tried for ≥ 4 weeks at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated: SSRI, SNRI, bupropion, mirtazapine, vilazodone (generic Viibryd®);

   4. Dose does not exceed both of the following (a and b): a. 120 mg per day; b. 1 capsule per day. Approval duration: 12 months Page 1 of 6

   CLINICAL POLICY
   Levomilnacipran 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: HIM.PA.33 for health insurance marketplace; 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: HIM.PA.103 for health insurance marketplace; 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: HIM.PA.154 for health insurance marketplace.
      II. Continued Therapy A. Major Depressive Disorder (must meet all):
   3. Member meets one of the following (a or b): 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);
4. Member is responding positively to therapy;

5. If request is for a dose increase, new dose does not exceed both of the following: a. 120 mg per day; b. 1 capsule per day. 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: HIM.PA.33 for health insurance marketplace; 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: HIM.PA.103 for health insurance marketplace; 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: HIM.PA.154 for health insurance marketplace. Page 2 of 6

   CLINICAL POLICY
   Levomilnacipran 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 policy – HIM.PA.154 or evidence of coverage documents; B. Fibromyalgia. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration MAOI: monoamine oxidase inhibitor SNRI: serotonin and norepinephrine reuptake inhibitor SSRI: selective serotonin reuptake inhibitor 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 bupropion (Wellbutrin® XL) mirtazapine (Remeron®) vilazodone (Viibryd®) 150-450 mg PO QAM 15-45 mg PO QHS 10 mg PO QD for 7 days, followed by 20 mg PO QD SSRIs citalopram (Celexa®)
   20 mg PO QD
   escitalopram (Lexapro®)
   10-20 mg PO QD
   Fluvoxamine® (Luvox CR®)
   50-300 mg PO QD
   fluoxetine (Prozac®)
   20 mg PO QD
   paroxetine (Paxil®)
   20 mg PO QD
   paroxetine controlled release (Paxil CR®) 25 mg PO QD
   sertraline (Zoloft®)
   50 mg PO QD
   SNRIs desvenlafaxine (Pristiq®) duloxetine (Cymbalta®) 50 mg PO QD 20 mg PO BID, 30 mg BID, or 60 mg PO QD 75 mg PO BID to TID Dose Limit/ Maximum Dose 450 mg/day 45 mg/day 40 mg per day 40 mg/day
   20 mg/day
   300 mg/day
   80 mg/day
   50 mg/day
   62.5 mg/day
   200 mg/day
   400 mg/day 120 mg/day venlafaxine (Effexor®) 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. 225 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Hypersensitivity to levomilnacipran, milnacipran HCl, or any excipient;
   o Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with Fetzima or within 7 days of stopping treatment with Fetzima. Do not Page 3 of 6

   CLINICAL POLICY
   Levomilnacipran use Fetzima within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start Fetzima in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. • Boxed warning(s): Increased risk of suicidal thoughts and behavior in pediatric and young adults taking antidepressants; closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors; not approved for use in pediatric patients. Appendix D: States with Limitations against Redirections in Certain Mental Health Settings State Step Therapy Notes Prohibited? No TX Applies to HIM requests only Failure of ONE of the following, used for ≥ 4 weeks at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated: SSRI, SNRI, bupropion, mirtazapine, vilazodone (generic Viibryd®) V. Dosage and Administration Indication Major depressive disorder
   Dosing Regimen 40 mg-120 mg PO QD Maximum Dose 120 mg/day VI. Product Availability
   Extended-release capsules: 20 mg, 40 mg, 80 mg, 120 mg VII.