Clinical Policy: ER (Aplenzin) Reference Number: ERX.ST.02 Effective Date: 06.01.15 Last Review Date: 08.17 Line of Business: Commercial [Prescription Drug Plan] Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description Bupropion ER (Aplenzin®) is an aminoketone .

FDA approved indication Aplenzin is indicated for the treatment of major depressive disorder and seasonal affective disorder.

Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria

It is the policy of health plans affiliated with Envolve Pharmacy Solutions™ that Aplenzin is medically necessary when the following criteria are met:

I. Initial Approval Criteria A. Step Therapy for Aplenzin (must meet all): 1. Age ≥ 18 years; 2. Previous use of ≥ 30 days of bupropion IR, SR, or XL, unless contraindicated or clinically significant adverse effects are experienced; 3. If request is for Aplenzin 522 mg, previous use of ≥ 30 days of one selective (SSRI) or serotonin/ reuptake inhibitor (SNRI), unless contraindicated or clinically significant adverse effects are experienced; 4. One of the aforementioned trials occurred within the last 6 months, unless all are contraindicated or clinically significant adverse effects are experienced; 5. Dose does not exceed 522 mg/day (1 tablet/day). Approval duration: 12 months

II. Continued Therapy A. Step Therapy for Aplenzin (must meet all): 1. Currently receiving medication via a health plan affiliated with Envolve Pharmacy Solutions or member has previously met initial approval criteria; 2. If request is for a dose increase, new dose does not exceed 522 mg/day (1 tablet/day). Approval duration: 12 months

III. Appendices/General Information Appendix A: Abbreviation/Acronym Key ER: extended-release SNRI: serotonin/norepinephrine reuptake inhibitor FDA: Food and Drug Administration SSRI: selective serotonin reuptake inhibitor

Appendix B: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/ Maximum Dose Bupropion IR (Wellbutrin) Major Depressive Disorder 300 mg/day 100 mg PO BID; titrate after 3 days to 100 mg PO TID if needed

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Drug Dosing Regimen Dose Limit/ Maximum Dose Bupropion SR (Wellbutrin Major Depressive Disorder 400 mg/day SR) 150 mg PO QD; titrate after 4 days to 150 mg PO BID then 200 mg PO BID after several weeks if needed Bupropion XL (Wellbutrin Major Depressive Disorder Major Depressive Disorder XL, Forfivo XL) Wellbutrin XL: 150 mg PO QD; titrate 450 mg/day after 4 days to 300 mg PO QD Forfivo XL: 450 mg PO QD Seasonal Affective Disorder Seasonal Affective Disorder 300 mg/day 150 mg PO QD; may increase to 300 mg PO QD after 7 days SSRIs (Celexa) Depression 40 mg/day (≤ 60 years) 20 mg PO QD; may increase to 40 mg 20 mg/day (> 60 years) PO QD after one week (Lexapro) Depression 20 mg/day 10 mg PO QD; may increase to 20 mg PO QD after 1 week (Prozac, Depression Prozac: 80 mg/day Prozac Weekly) Prozac: 20 mg PO QD; may increase by 10-20 mg after several weeks Prozac Weekly: 90 mg/week Prozac Weekly: 90 mg PO q week beginning 7 days after the last daily dose (Paxil, Paxil Depression Paxil, Paxeva: 50 mg/day CR, Pexeva) Paxil, Paxeva: 20 mg PO QD; may increase by 10 mg every week as Paxil CR: 62.5 mg/day needed

Paxil CR: 25 mg PO QD; may increase by 12.5 mg every week as needed (Zoloft) Depression 200 mg/day 50 mg PO QD; may increase every week as needed SNRIs (Cymbalta) Depression 120 mg/day 20 mg PO BID or 30 mg PO BID or 60 mg PO QD (Effexor, Depression Effexor: 225 mg/day Effexor XR) Effexor: 75 mg/day PO in 2-3 divided (outpatient) or 375 mg/day doses; may increase by 75 mg every 4 (inpatient) days as needed Effexor XR: 225 mg/day Effexor XR: 75 mg PO QD; may increase by 75 mg every 4 days as needed (Pristiq, Depression 400 mg/day Khedezla) 50 mg PO QD Levomilnacipran Depression 120 mg/day (Fetzima) 20 mg PO QD for 2 days, then 40 mg PO QD; may increase by 40 mg every 2 days

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IV. Dosage and Administration Indication Dosing Regimen Maximum Dose Major depressive disorder 174 mg PO QD, may increase to 348 mg 522 mg/day Seasonal affective disorder PO QD after 4 days 348 mg/day

V. Product Availability Extended-release tablets: 174 mg, 348 mg, 522 mg

VI. References 1. Aplenzin Prescribing Information. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; August 2016. Available at: www.aplenzin.com. Accessed June 28, 2017.

Reviews, Revisions, and Approvals Date P&T Approval Date Policy created 06.15 06.15 Updated to new template (converted algorithm to bulleted 07.16 09.16 criteria, added background and references). Converted to new template. Added that one of the trials must 06.17 08.17 have occurred within the last 6 months. Removed requirement that SSRI/SNRI must be PDL to allow credit for other non-PDL SSRI/SNRIs trialed.

Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information.

This Clinical Policy is not intended to dictate to providers how to practice medicine, nor does it constitute a contract or guarantee regarding payment or results. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members.

This policy is the property of Envolve Pharmacy Solutions. Unauthorized copying, use, and distribution of this Policy or any information contained herein is strictly prohibited. By accessing this policy, you agree to be bound by the foregoing terms and conditions, in addition to the Site Use Agreement for Health Plans associated with Envolve Pharmacy Solutions.

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