LUCEMYRA, Lofexidine HCl Form

Lofexidine (Lucemyra™) is a central alpha-2 adrenergic agonist. FDA Approved Indication(s) Lucemyra is indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation 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 Lucemyra is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Opioid Withdrawal (must meet all):

1. Diagnosis of opioid dependence or opioid use disorder;
   2. Prescribed by or in consultation with a physician specializing in one of the following areas: emergency medicine/inpatient care, pain management, or addiction psychiatry;
2. Age ≥ 18 years;
   
   4. Member is undergoing or is scheduled to undergo abrupt opioid discontinuation within the next seven days, and meets one of the following (a or b): a. Current use of ≥ 1 opioid for > 3 weeks; b. Received or planned administration of an opioid antagonist (e.g., naltrexone) after a period of opioid use;
3. Medical justification supports inability to use an opioid taper (e.g., buprenorphine, methadone);
4. Member meets one of the following (a or b): a. Failure of clonidine, unless contraindicated or clinically significant adverse effects are experienced; b. Lucemyra was initiated in an inpatient setting (e.g., emergency department);
   7. Lucemyra has not been prescribed for a prior opioid withdrawal event within the last 30 days, or medical justification supports retreatment;
5. Total number of tablets per duration per course of treatment does not exceed 224 tablets per 14 days;

6. Dose does not exceed 2.88 mg (16 tablets) per day. Approval duration: 7 days (112 tablets)
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   CLINICAL POLICY Lofexidine B. 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. Opioid Withdrawal (must meet all):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Lucemyra for a covered indication and has received this medication for less than 14 days;
10. Member is responding positively to therapy;
    3. Total number of tablets per duration per course of treatment does not exceed 224 tablets per 14 days;
11. If request is for a dose increase, new dose does not exceed 2.88 mg (16 tablets) per day. Approval duration: 7 days (112 tablets)
    B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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 Page 2 of 7

    CLINICAL POLICY Lofexidine 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.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key APA: American Psychiatric Association ASAM: American Society of Addiction Medicine
    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.
    Drug Name Dosing Regimen Oral IR tablet: clonidine (Catapres® 0.1, 0.2 and 0.3 mg immediate release [IR] tablet) Transdermal patch: clonidine (Catapres®-TTS-1, TTS-2 or TTS-3 representing 0.1, 0.2 and 0.3 mg/24 hr)
    Opioid withdrawal symptoms (off-label) American Psychiatric Association (APA) 2006 guidelines:
    • 0.1 mg TID is usually sufficient to suppress signs of opioid withdrawal although inpatients can generally receive higher doses to block withdrawal symptoms because of the availability hypotension and sedation monitoring (formulation not specified). • Outpatients should not be given more than a 3- day supply of clonidine for unsupervised use because treatment requires careful dose titration and clonidine overdoses can be life-threatening. American Society of Addiction Medicine (ASAM) 2015 guidelines:
    • 0.1–0.3 mg every 6–8 hours (IR tablet or transdermal patch [see package insert for detailed transdermal patch dosing information including maximum dose per day]). Dose Limit/ Maximum Dose Outpatient use: 0.3 mg/day; 3- day supply (APA 2006) General treatment course duration: 4-6 days (APA 2006) 1.2 mg/day (ASAM 2015) 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. Page 3 of 7

    CLINICAL POLICY Lofexidine Appendix C: Contraindications/Boxed Warnings None reported Appendix D: Opioid Withdrawal - DSM-5 DSM-5 diagnostic criteria for opioid withdrawal are as follows:
    A. Presence of either of the following: • Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e., several weeks or longer). • Administration of an opioid antagonist after a period of opioid use. B. Three (or more) of the following developing within minutes to several days after Criterion A: • Dysphoric mood • Nausea or vomiting • Muscle aches • Lacrimation or rhinorrhea • Pupillary dilation, piloerection, or sweating • Diarrhea • Yawning • Fever • Insomnia C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance. V. Dosage and Administration
    Indication Dosing Regimen Opioid withdrawal
    • Usual starting dosage: three 0.18 mg tablets PO QID during peak withdrawal symptoms (generally the first 5 to 7 days following last use of opioid) - dosing guided by symptoms and side effects; 5 to 6 hours between each dose; with or without food.
    • Discontinue with a gradual dose reduction over a 2- to 4-day period to mitigate Lucemyra withdrawal symptoms (e.g., reducing by 1 tablet per dose every 1 to 2 days).
    • Dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity to Lucemyra side effects. Maximum Dose Per dose: 0.72 mg (4 tablets) Per day: 2.88 mg (16 tablets) Maximum number of days: 14
    Maximum number of tablets: 224 VI. Product Availability
    Tablet: 0.18 mg Page 4 of 7

    CLINICAL POLICY Lofexidine VII.