PROTOPIC, Tacrolimus (Topical) ELIDEL, Pimecrolimus Form

The following are topical immunomodulators requiring prior authorization: pimecrolimus (Elidel®) and tacrolimus (Protopic®).
FDA Approved Indication(s) Topical immunomodulators are indicated as second-line therapy for the short-term and non- continuous chronic treatment of atopic dermatitis in non-immunocompromised adults and children who have failed to respond adequately to other topical prescription treatments for atopic dermatitis, or when those treatments are not advisable. • Elidel cream is specifically indicated for mild to moderate disease in patients 2 years of age and older. • Protopic ointment is specifically indicated for moderate to severe disease.
Limitation(s) of use: Protopic ointment and Elidel cream are not indicated for children younger than 2 years of age. Policy/Criteria Provider must submit documentation (including 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 Protopic and Elidel/generics are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Atopic Dermatitis or Vitiligo (must meet all):

1. Diagnosis of atopic dermatitis or vitiligo;
2. If request is for tacrolimus 0.03% ointment or pimecrolimus, member is ≥ 2 years of age;
   3. If request is for tacrolimus 0.1% ointment, member is ≥ 16 years of age;

3. If request is for brand Protopic or Elidel, member must use generic topical tacrolimus or pimecrolimus, unless clinically significant adverse effects are experienced or both are contraindicated;

   5. Member meets one of the following (a, b, or c): a. Children and adolescents: Failure of 2 medium potency topical corticosteroids in the previous 6 months, unless all are contraindicated or clinically significant adverse effects are experienced; Page 1 of 8

   CLINICAL POLICY
   Topical Immunomodulators b. Adults: Failure of 2 high or very high potency topical corticosteroids in the previous 6 months, unless all are contraindicated or clinically significant adverse effects are experienced; c. Use on the face or skinfolds;

   6. Request does not exceed health plan-approved quantity limit.Refer to Health Plan PDL or formulary Approval duration:
      HIM/Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less B. Plaque Psoriasis (off-label) (must meet all):
   7. Diagnosis of plaque psoriasis;
4. Age ≥ 2 years;

5. Prescribed for use on face or intertriginous areas (e.g., genitals, armpits, forearms, and groin);

   4. If request is for brand Protopic or Elidel, member must use generic topical tacrolimus or pimecrolimus, unless clinically significant adverse effects are experienced or both are contraindicated;
   5. Request does not exceed health plan-approved quantity limit.Refer to Health Plan PDL or formulary Approval duration:
      HIM/Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less C. Other diagnoses/indications (must meet 1 or 2):
   6. 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
   7. 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. All Indications in Section I (must meet all):
   8. Member meets one of the following (a or b): Page 2 of 8

   CLINICAL POLICY
   Topical Immunomodulators 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);

6. Member is responding positively to therapy;

7. If request is for brand Protopic or Elidel, member must use generic topical tacrolimus or pimecrolimus, unless clinically significant adverse effects are experienced or both are contraindicated;

   4. If request is for a dose increase, new dose does not health plan-approved quantity limit.Refer to Health Plan PDL or formulary Approval duration:
      HIM/Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
   5. 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
   6. 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.154for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation Key AAD: American Academy of Dermatology FDA: Food and Drug Administration NPF: National Psoriasis Foundation Page 3 of 8

   CLINICAL POLICY
   Topical Immunomodulators 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 augmented betamethasone 0.05% (Diprolene) gel clobetasol propionate 0.05% (Temovate ) cream, ointment, gel, solution diflorasone diacetate 0.05% (Apexicon®Psorcon) ointment halobetasol propionate 0.05% (Ultravate) cream, ointment augmented betamethasone 0.05% (Diprolene AF, Diprolene®) cream, ointment, lotion diflorasone 0.05% (Apexicon®Psorcon ) cream fluocinonide acetonide 0.05% cream, ointment, gel, solution triamcinolone acetonide 0.5% cream, ointment desoximetasone 0.25% (Topicort®) cream, ointment desoximetasone 0.05% (Topicort ) cream, gel fluocinolone acetonide 0.025% (Synalar) cream, ointment mometasone 0.1% (Elocon) cream, ointment, lotion triamcinolone acetonide 0.025%, 0.1% cream, ointment 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. Apply topically to the affected area(s) BID Should not be used for longer than 2 - 3 consecutive weeks Appendix C: Contraindications/Boxed warnings • Contraindication(s): hypersensitivity to the active ingredient or any other component of the product Page 4 of 8

   CLINICAL POLICY
   Topical Immunomodulators • Boxed warning(s): long-term safety of topical calcineurin inhibitors has not been established o Although a casual relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients with topical calcineurin inhibitors. Therefore:
    Continuous long-term use of topical calcineurin inhibitors in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis
    Not indicated for use in children less than 2 years of age Appendix D: General Information • On March 10, 2005, the FDA issued a public health advisory about a potential cancer risk from Elidel. The FDA recommends that Elidel should be used second-line, avoided in children below the age of 2, and used in minimum amounts intermittently to control symptoms. Black box warning and Medication Guide for patients have been instituted, as recommended by the FDA. • A Consensus Conference on Atopic Dermatitis sponsored by the American Academy of Dermatology recommended that topical immunomodulator agents should be reserved for second line therapy in patients who fail standard interventions, including low to mid potency topical corticosteroids. • The 2021 American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) guidelines for the management and treatment of psoriasis with topical therapy recommendations:
   o 2.1 The off-label usage of 0.1% tacrolimus for psoriasis involving the face as well as inverse psoriasis for up to 8 weeks can be considered.
   o 2.2 The off-label use of pimecrolimus for inverse psoriasis for 4-8 weeks is recommended.
   • The 2020 AAD and NPF guideline for the management and treatment of psoriasis in pediatric patients recommendations:
   o 11.1 Tacrolimus 0.1% ointment is recommended for off-label use as monotherapy for pediatric psoriasis of the face and genital region. V. Dosage and Administration Drug Elidel Protopic Dosing Regimen A thin layer topically to affected skin BID A thin layer topically to affected skin BID Maximum Dose 30 gm tube/month 30 gm tube/month VI. Product Availability Drug Elidel Protopic Availability
   Cream: 1% Ointment: 0.03%, 0.1% Page 5 of 8

   CLINICAL POLICY
   Topical Immunomodulators VII.