ABSORICA, Isotretinoin AMNESTEEM, Isotretinoin MYORISAN, Isotretinoin ZENATANE, Isotretinoin CLARAVIS, Isotretinoin Form

Isotretinoin (Absorica®, Absorica LD™, Amnesteem®, Claravis™, Myorisan™, Zenatane®) is a systemic retinoid. FDA Approved Indication(s) Absorica, Absorica LD, Amnesteem, Claravis, Myorisan, and Zenatane are indicated for severe recalcitrant nodular acne. Absorica and Absorica LD are specifically indicated in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Limitation(s) of use: If a second course of Absorica/Absorica LD therapy is needed, it is not recommended before a two-month waiting period because the patient’s acne may continue to improve following a 15 to 20-week course of therapy. 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 Absorica, Absorica LD, Amnesteem, Claravis, Myorisan, and Zenatane are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acne (must meet all):

1. Diagnosis of nodular acne;
   2. Age ≥ 12 years;
   3. Failure of ≥ 2 of the following topical agents (must be from 2 different classes listed below), unless clinically significant adverse effects are experienced or all are contraindicated:
      a. Topical antibiotics: clindamycin, erythromycin; b. Topical anti-infectives: benzoyl peroxide 10% gel, benzoyl peroxide 10% lotion; c. Topical retinoids: tretinoin 0.025% gel, tretinoin 0.05% cream, tretinoin 0.1% cream;Prior authorization may be required for tretinoin

2. At least one of the topical agents above was used concurrently with one of the following oral antibiotics for ≥ 60 days: doxycycline, erythromycin, minocycline, Page 1 of 7

   CLINICAL POLICY Isotretinoin tetracycline, trimethoprim-sulfamethoxazole, unless clinically significant adverse effects are experienced or all are contraindicated;

3. If request is for Absorica or Absorica LD, member must use Myorisan, Amnesteem, Claravis, Zenatane, and generic isotretinoin unless clinically significant adverse effects are experienced or all are contraindicated;
   
   6. Dose does not exceed one of the following (a or b): a. Absorica, Amnesteem, Claravis, Myorisan, Zenatane: 2 mg/kg per day; b. Absorica LD: 1.6 mg/kg per day. Approval duration:
      Medicaid/HIM – 6 months
      Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
4. 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
5. 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 (must meet all):
6. 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. Member is responding positively to therapy;
   3. If member has received 20 consecutive weeks of treatment, an 8-week treatment-free interval must be allowed prior to reinitiating isotretinoin treatment;

7. If request is for Absorica or Absorica LD, member must use Myorisan, Amnesteem, Claravis, Zenatane, and generic isotretinoin unless clinicially significant adverse effects are experienced or all are contraindicated; Page 2 of 7

   CLINICAL POLICY Isotretinoin

8. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. Absorica, Amnesteem, Claravis, Myorisan, Zenatane: 2 mg/kg per day; b. Absorica LD: 1.6 mg/kg per day. Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
9. 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

10. 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 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 clindamycin 1% (Cleocin T®, Clindagel®, Clindamax®) erythromycin 2% (Erygel®) Gel, solution: Apply to the affected Gel, lotion, solution: Apply a thin film twice daily area twice daily Page 3 of 7 Dose Limit/ Maximum Dose Not applicable Not applicable

    CLINICAL POLICY Isotretinoin Drug Name Dosing Regimen benzoyl peroxide (Desquam- X®) liquid, gel and lotion tretinoin (Retin-A®) doxycycline erythromycin (EES®, Erythromycin Base®, Ery- Tab®) minocycline (Solodyn®) tetracycline Liquid, gel and lotion: Apply once daily to four times daily 0.025% gel, 0.05% cream, 0.1% cream: Apply once daily 50 to 100 mg PO daily 250 to 500 mg PO twice daily, followed by twice daily dosing IR: 100 mg PO twice daily ER: 1 mg/kg PO daily 125 to 250 mg PO every 6 hours for 2 weeks, then 125 to 500 mg PO daily or every other day As directed by physician Dose Limit/ Maximum Dose Not applicable Not applicable 300 mg per day 4 gm per day 200 mg per day 4 mg per day trimethoprim- sulfamethoxazole (Bactrim®) 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. 20 mg/kg/day of trimethoprim Appendix C: Contraindications/Boxed Warnings • Contraindication(s): pregnancy (category X), hypersensitivity to the medication or any of its components • Boxed warning(s): if pregnancy occurs during isotretinoin use, there is an extremely high risk for severe birth defects (iPLEDGE REMS program enrollment is required for prescribers, patients, pharmacies, and distributors) Appendix D: General Information
    • Micromedex classifies the use of isotretinoin for the non-FDA labeled indication of mild- to-moderate acne vulgaris as a Class IIa strength of recommendation. • The American Academy of Dermatology recognizes that isotretinoin is also useful for the management of lesser degrees of acne that are treatment-resistant or for the management of acne that is producing either physical or psychological scarring.
    • Micromedex classifies the use of isotretinoin for the non-FDA labeled indication of rosacea as a Class IIa strength of recommendation. • The American Acne and Rosacea Society Consensus Recommendations recognize that isotretinoin has been shown to be effective in treating some refractory cases of papulopustular rosacea, but therapeutic benefit may require continued use. Due to the limited data on the management of refractory rosacea, isotretinoin should only be considered in select cases. • Because of the risk of teratogenicity and to minimize fetal exposure, isotretinoin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called iPLEDGE. Isotretinoin must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Isotretinoin must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE. Page 4 of 7

    CLINICAL POLICY Isotretinoin Registered and activated pharmacies must receive isotretinoin only from wholesalers registered with iPLEDGE. For more information call 866-495-0654 or visit http://www.ipledgeprogram.com.
    V. Dosage and Administration
    Drug Name Isotretinoin (Absorica, Amnesteem, Claravis, Myorisan, Zenatane) Isotretinoin (Absorica LD) Acne Indication Dosing Regimen Acne 0.5 to 1 mg/kg/day PO given in two divided doses Maximum Dose 2 mg/kg/day 0.4 to 0.8 mg/kg/day PO given in two divided doses 1.6 mg/kg/day VI. Product Availability
    Drug Name Isotretinoin (Absorica)
    Isotretinoin (Absorica LD)
    Isotretinoin (Amnesteem) Isotretinoin (Claravis, Myorisan, Zenatane)
    Availability Capsules: 10 mg, 20 mg, 25 mg, 30 mg, 35 mg, and 40 mg
    Capsules: 8 mg, 16 mg, 20 mg, 24 mg, 28 mg, and 32 mg
    Capsules: 10 mg, 20 mg, 40 mg Capsules: 10 mg, 20 mg, 30 mg, and 40 mg
    VII.