Minocycline ER (Solodyn, Ximino, Minolira), Microspheres (Arestin), Foam (Zilxi) Form

Minocycline ER [extended release] (Solodyn®, Ximino®, Minolira™), microspheres (Arestin®), and foam (Zilxi®) are tetracycline-class drugs. ____ *For Health Insurance Marketplace (HIM) in all states except Florida, if request is through pharmacy benefit, Arestin is excluded and should not be approved using these criteria. FDA Approved Indication(s) Solodyn, Ximino, and Minolira are indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older.
Limitation(s) of use: Solodyn, Ximino, and Minolira did not demonstrate any effect on non- inflammatory acne lesions. Safety of these drugs have not been established beyond 12 weeks of use. These formulations of minocycline have not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, Solodyn, Ximino, and Minolira should be used only as indicated. Arestin is indicated as an adjunct to scaling and root planing procedures for reduction of pocket depth in patients with adult periodontitis. Arestin may be used as part of a periodontal maintenance program which includes good oral hygiene and scaling and root planing. Zilxi is indicated for the treatment of inflammatory lesions of rosacea in adults. Limitation(s) of use: Zilxi has not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, Zilxi should be used only as indicated. 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 Solodyn, Ximino, Minolira, Arestin, and Zilxi are medically necessary when the following criteria are met:
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CLINICAL POLICY Minocycline I. Initial Approval Criteria
A. Acne Vulgaris (must meet all):

1. Diagnosis of acne vulgaris;
2. Request is for Solodyn, Ximino, or Minolira;
3. Age ≥ 12 years;
4. Member must use immediate-release minocycline, unless contraindicated or clinically significant adverse effects are experienced;
   5. Failure of a ≥ 4 week trial of one additional preferred oral tetracycline antibiotic (e.g., immediate-release doxycycline), unless clinically significant adverse effects are experienced or all are contraindicated;
5. Dose does not exceed 135 mg per day.
   Approval duration: 12 weeks B. Periodontitis (must meet all):
   
   1. Diagnosis of chronic periodontitis (also known as adult periodontitis);
6. Request is for Arestin;
7. Prescribed by or in consultation with a periodontist;
8. Age ≥ 18 years;
9. Intolerance or contraindication to oral doxycycline hyclate at a sub-antimicrobial dose (20 mg PO twice a day) (e.g., unable to swallow capsules, allergic to a doxycycline product excipient, history of gastrointestinal disease);
   6. Prescribed as an adjunct to a scaling and root planing procedure to reduce pocket depth (applied during procedure);
   7. Dose is individualized depending on the size, shape, and number of pockets being treated. Approval duration:
      Medicaid/Commercial – 1 procedure HIM – Arestin is excluded in all states except Florida; in Florida, approval is for 1 procedure C. Rosacea (must meet all):
   8. Diagnosis of rosacea with inflammatory lesions (papules and pustules);
10. Request is for Zilxi;
11. Age ≥ 18 years;
12. Failure of ≥ 6 consecutive weeks of two of the following (see Appendix B) at maximally tolerated doses, unless clinically significant adverse effects are experienced or all are contraindicated: oral doxycycline, topical metronidazole, topical ivermectin, topical azelaic acid;

13. Dose does not exceed 1 can per month. Approval duration:
    Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less Page 2 of 10

    CLINICAL POLICY Minocycline D. 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: 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
    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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       II. Continued Therapy A. Acne Vulgaris (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);
14. Request is for Solodyn, Ximino, or Minolira;
15. Member is responding positively to therapy;
16. If request is for a dose increase, new dose does not exceed 135 mg per day.
    Approval duration: 12 weeks B. Periodontitis (must meet all):
    
    1. 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);
    2. Request is for Arestin;
17. Member has not received 4 scaling and root planing procedures in the last 365 days;

18. Dose is individualized depending on the size, shape, and number of pockets being treated. Approval duration:
    Medicaid/Commercial – 1 procedure HIM – Arestin is excluded in all states except Florida; in Florida, approval is for 1 procedure
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    CLINICAL POLICY Minocycline C. Rosacea (must meet all):

    1. 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);
    2. Request is for Zilxi;
19. Member is responding positively to therapy;

20. If request is for a dose increase, new dose does not exceed 1 can per month. 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):

    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: 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
    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: 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 FDA: Food and Drug Administration Page 4 of 10

    CLINICAL POLICY Minocycline 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 Varies Acne Vulgaris Adults, adolescents, and children 8 years and older weighing 45 kg or more: 100 mg PO every 12 hours on day 1, then 100 mg PO once daily Children 8 years and older and adolescents weighing less than 45 kg: 2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily Acne Vulgaris Adults: 200 mg PO initially, then 100 mg PO every 12 hours as adjunctive therapy. Alternatively, if more frequent oral doses are preferred, 100 to 200 mg PO initially, then 50 mg PO every 6 hours Children ≥ 8 years and adolescents: 4 mg/kg PO (max: 200 mg) initially, then 2 mg/kg/dose PO every 12 hours (max: 100 mg/dose) as adjunctive therapy Acne Vulgaris Adults: 1 g/day PO in divided doses, then decrease slowly to 125 to 500 mg PO daily or every other day Children ≥ 9 years and adolescents: 1 g/day PO in divided doses, then decrease slowly to 125 to 500 mg PO daily or every other day Periodontitis 20 mg BID (subantimicrobial-dose) for 3 to 9 months Rosacea Apply thin film topically to affected area QD for 1% and BID for 0.75% 200 mg/day Varies 40 mg/day Not applicable
    Not applicable doxycycline (Vibramycin) minocycline (Minocin)
    tetracycline
    doxycycline (Periostat®) metronidazole
    (Metrocream® 0.75%, Metrogel® 1%, Metrolotion® 0.75%) azelaic acid (Finacea® 15% gel) doxycycline (Oracea®) Rosacea Apply in a thin film topically to the affected area BID Reassess if no improvement in 12 weeks Rosacea 40 mg PO once daily in the morning (1 hour before or 2 hours after a meal) Rosacea Apply pea size amount to the affected areas of the face QD Soolantra® (ivermectin cream) 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. 300 mg/day PO; 40 mg PO/day for Oracea 1 g/day Page 5 of 10

    CLINICAL POLICY Minocycline Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to minocycline or any tetracyclines
    • Boxed warning(s): none reported Appendix D: General Information • Arestin is a variable dose product, dependent on the size, shape, and number of pockets being treated. In US clinical trials, up to 122 unit-dose cartridges were used in a single visit and up to 3 treatments, at 3-month intervals, were administered in pockets with pocket depth of 5 mm or greater. • The 2015 American Dental Association guidelines rank the following drug therapies as adjuncts to scaling and root planing for chronic periodontitis (rankings in order of strength are 1) strong, 2) in favor, 3) weak, 4) expert opinion for, 5) expert opinion against, 6) against): o “In favor”:  Systemic subantimicrobial-dose doxycycline o “Weak”:  Systemic antimicrobials at standard doses (similar benefit to subantimicrobial Maximum Dose 1 mg/kg/day PO up to 135 mg/day PO doses but increased risk of adverse effects)  Chlorhexidine chips (locally applied)  Photodynamic therapy with diode laser o “Expert opinion for”
     Doxycycline hyclate gel (locally applied)  Minocycline microspheres (locally applied) V. Dosage and Administration
    Drug Name Indication Dosing Regimen Acne vulgaris Minocycline extended release tablets (Solodyn) The recommended dosage is approximately 1 mg/kg PO once daily for 12 weeks. The following table shows tablet strength and body weight to achieve approximately 1 mg/kg: Wt. (lbs) Wt. (kg) Tablet Strength (mg) 45 Actual mg/kg dose 1- 0.92 1.10- 0.93 1.08- 0.92 1.11- 0.95 1.06- 0.94 55 65 80 90 99-109 45-49 110-131 50-59 132-157 60-71 158-186 72-84 187-212 85-96 Page 6 of 10

    CLINICAL POLICY Minocycline Drug Name Indication Dosing Regimen 213-243 97-110 105 244-276 111-125 115 277-300 126-136 135 1.08- 0.95 1.04- 0.92 1.07- 0.99 Acne vulgaris Minocycline extended release capsules (Ximino) The recommended dosage is approximately 1 mg/kg PO once daily for 12 weeks. The following table shows capsule strength and body weight to achieve approximately 1 mg/kg: Wt. (lbs) Wt. (kg) Capsule Strength (mg) 45 99-131 45-59 Actual mg/kg dose 1- 0.76 1.5-1 1.48- 0.99 132-199 60-90 200-300 91-136 90 135 Periodontitis Arestin is a variable dose product, Minocycline microspheres (Arestin) dependent on the size, shape, and number of pockets being treated. In US clinical trials, up to 122 unit-dose cartridges were used in a single visit and up to 3 treatments, at 3- month intervals, were administered in pockets with pocket depth of 5 mm or greater. _ Arestin is provided as a dry powder, packaged in a unit-dose cartridge with a deformable tip, which is inserted into a spring-loaded cartridge handle mechanism to administer the product. The oral health care professional removes the disposable cartridge from its pouch and connects the cartridge to the handle mechanism.
    The recommended dosage is approximately 1 mg/kg PO once daily for 12 weeks. The following list shows tablet strength and body weight to achieve approximately 1 mg/kg: Weight (kg): tablet strength (mg) 45-59 kg: half of the 105 mg tablet 60-89 kg: half of the 135 mg tablet 90-125 kg: 105 mg Page 7 of 10 Acne vulgaris Minocycline extended release tablets (Minolira) Maximum Dose 1 mg/kg/day PO up to 135 mg/day PO Dose is variable depending on size, shape, and number of pockets being treated. 1 mg/kg/day PO up to 135 mg/day PO

    CLINICAL POLICY Minocycline Drug Name Indication Dosing Regimen Minocycline foam (Zilxi) Rosacea 126-136 kg: 135 mg Apply as a thin layer to affected areas of the face once daily. Gently rub into skin.
    Maximum Dose One application/ day VI. Product Availability
    Drug Name Minocycline extended release tablets (Solodyn) Minocycline extended release capsules (Ximino) Minocycline extended release tablets (Minolira) Minocycline microspheres (Arestin) Minocycline foam (Zilxi) †Available as generic only Availability Extended-release tablets: 45 mg†, 55 mg, 65 mg, 80 mg, 90 mg†, 105 mg, 115 mg, and 135 mg† Extended-release capsules: 45 mg, 90 mg, and 135 mg Extended-release tablets: 105 mg and 135 mg Unit-dose cartridge: minocycline hydrochloride microspheres equivalent to 1 mg of minocycline free base (1 or 12 unit-dose cartridges per box) Foam: 1.5% (30 g can) VII.