Roflumilast (Daliresp) Form

Roflumilast (Daliresp® , Zoryve®) is a selective phosphodiesterase 4 inhibitor. FDA Approved Indication(s) Daliresp is indicated as a treatment to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Zoryve cream is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. Zoryve foam is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older.
Limitation(s) of use:
• Daliresp is not a bronchodilator and is not indicated for the relief of acute bronchospasm.
• Daliresp 250 mcg is a starting dose for the first 4 weeks of treatment only and is not the effective (therapeutic) dose. 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 Daliresp and Zoryve are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Obstructive Pulmonary Disease (must meet all):

1. Request is for roflumilast tablet (Daliresp);
   2. Diagnosis of COPD;
   3. Age ≥ 18 years;
   4. Current (within the past 30 days) forced expiratory volume in one second (FEV1) < 50% predicted;

2. Member meets one of the following (a or b): a. Failure of triple inhaled therapy consisting of a combination of a long-acting beta2-agonist (LABA), long-acting antimuscarinic antagonist (LAMA), and inhaled corticosteroid (ICS) at up to maximally indicated doses; Page 1 of 11

   CLINICAL POLICY Roflumilast b. Both i and ii: i. Failure of dual inhaled therapy consisting of a combination of a LABA and LAMA at up to maximally indicated doses; ii. Current (within the past 30 days) blood eosinophil count < 100 cells/uL;

3. Daliresp is prescribed concurrently with a long-acting bronchodilator (i.e., LABA or LAMA);
4. For brand Daliresp requests, member must use generic roflumilast, unless contraindicated or clinically significant adverse effects are experienced;
5. Dose does not exceed both of the following (a and b): a. 500 mcg per day; b. 1 tablet per day. Approval duration: 12 months B. Plaque Psoriasis (must meet all):
6. Request is for roflumilast cream (Zoryve);
   2. Diagnosis of plaque psoriasis with body surface area involvement ≤ 20%;
   3. Prescribed by or in consultation with a dermatologist or rheumatologist;
   4. Age ≥ 6 years;
   5. Member meets one of the following (a or b):
      a. Failure of both (i and ii) used concurrently, unless clinically significant adverse effects are experienced or all are contraindicated:
      i. Medium to ultra-high potency topical corticosteroid (see Appendix B); ii. Calcipotriene, calcitriol, or tazarotene;
      b. For face or intertriginous areas (e.g., genitals, armpits, forearms, and groin): Failure of a topical calcineurin inhibitor (see Appendix B), unless contraindicated or clinically adverse effects are experienced;
      Prior authorization may be required for topical calcineurin inhibitors
7. Request does not exceed 1 tube per month.
   Approval duration: 12 months C. Seborrheic Dermatitis (must meet all):
8. Request is for roflumilast foam (Zoryve);
   2. Diagnosis of seborrheic dermatitis with body surface area involvement ≤ 20%;
   3. Prescribed by or in consultation with a dermatologist;
   4. Age ≥ 9 years;
   5. Failure of both of the following (a and b), unless clinically significant adverse effects are experienced or all are contraindicated:
      a. Topical antifungal (see Appendix B);
      b. Topical corticosteroid (see Appendix B);
9. Request does not exceed 1 can per month.
   Approval duration: 12 months
   D. Other diagnoses/indications (must meet 1 or 2):

10. 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): Page 2 of 11

    CLINICAL POLICY Roflumilast 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

11. 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. Chronic Obstructive Pulmonary Disease (must meet all):
12. 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 receiving benefit from the referenced states for the applicable product and regulation (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
13. Request is for roflumilast tablet (Daliresp);
    3. Member is responding positively to therapy;
    4. For brand Daliresp requests, member must use generic roflumilast, unless contraindicated or clinically significant adverse effects are experienced;
14. If request is for a dose increase, new dose does not exceed both of the following (a and b):
    a. 500 mcg per day; b. 1 tablet per day. Approval duration: 12 months B. Plaque Psoriasis (must meet all):
15. 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 receiving benefit from the referenced states for the applicable product and regulation (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
16. Request is for roflumilast cream (Zoryve);
    3. Member is responding positively to therapy;
    4. If request is for a dose increase, new dose does not exceed 1 tube per month. Approval duration: 12 months C. Seborrheic Dermatitis (must meet all):

17. Member meets one of the following (a or b): Page 3 of 11

    CLINICAL POLICY Roflumilast a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is receiving benefit from the referenced states for the applicable product and regulation (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

18. Request is for roflumilast foam (Zoryve);
    3. Member is responding positively to therapy;
    4. If request is for a dose increase, new dose does not exceed 1 can per month. Approval duration: 12 months D. Other diagnoses/indications (must meet 1 or 2):
19. 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

20. 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 COPD: chronic obstructive pulmonary disease FDA: Food and Drug Administration FEV1: forced expiratory volume in one second ICS: inhaled corticosteroid
    LABA: long-acting beta2-agonist LAMA: long-acting antimuscarinic antagonist
    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.
    Page 4 of 11

    CLINICAL POLICY Roflumilast COPD Drug Name fluticasone/salmeterol (Advair Diskus®) Breo Ellipta® (fluticasone/ vilanterol) budesonide/formoterol (Symbicort®) Dulera®*(mometasone/ formoterol) Bevespi Aerosphere® (formoterol/glycopyrrolate) Utibron Neohaler® (indacaterol/glycopyrrolate) Anoro Ellipta® (vilanterol/umeclidinium) Stiolto Respimat® (olodaterol/tiotropium) Tudorza Pressair® (aclidinium bromide) Seebri Neohaler® (glycopyrrolate) Spiriva Respimat®/ HandiHaler® (tiotropium) Incruse Ellipta (umeclidinium) Brovana® (arformoterol) Arcapta Neohaler® (indacaterol) Striverdi Respimat® (olodaterol) Serevent Diskus® (salmeterol) Trelegy™ Ellipta® (fluticasone/umeclidinium/ vilanterol) Dosing Regimen ICS/LABA Combinations Refer to prescribing information Doses of 10 mcg formoterol/400 mcg mometasone and 10 mcg formoterol/ 200 mcg mometasone, each inhaled BID, have been studied LABA/LAMA Combinations
    Refer to prescribing information LAMAs Refer to prescribing information LABAs Refer to prescribing information Dose Limit/ Maximum Dose Refer to prescribing information The optimal dose has not been established Refer to prescribing information Refer to prescribing information Refer to prescribing information ICS/LABA/LAMA Combinations 1 inhalation by mouth QD
    1 inhalation/day Page 5 of 11

    CLINICAL POLICY Roflumilast Plaque Psoriasis
    Drug Name Dosing Regimen Apply topically to the affected area(s) BID Apply topically to the affected area(s) BID Apply topically to the affected area(s) QHS Apply topically to the affected area(s) BID calcipotriene (Dovonex®) cream, ointment, solution calcitriol (Vectical™) ointment tazarotene (Tazorac®) gel, cream Ultra-High Potency Topical Corticosteroids augmented betamethasone dipropionate 0.05% (Diprolene®, Alphatrex®) ointment, gel clobetasol propionate 0.05% (Temovate®, Temovate E®) cream, ointment, gel, solution diflorasone diacetate 0.05% (Apexicon®) ointment Apply topically to the affected area(s) BID halobetasol propionate 0.05% (Ultravate®) cream, ointment High Potency Topical Corticosteroids augmented betamethasone dipropionate 0.05% (Diprolone®, Diprolene® AF) cream, lotion betamethasone dipropionate 0.05% ointment desoximetasone (Topicort®) 0.25%, 0.05% cream, ointment, gel diflorasone 0.05% (Apexicon E®) cream fluocinonide acetonide 0.05% cream, ointment, gel, solution triamcinolone acetonide 0.5% (Aristocort®, Kenalog®) cream, ointment Medium/Medium to High Potency Topical Corticosteroids betamethasone dipropionate 0.05% cream Apply topically to the affected area(s) BID Dose Limit/ Maximum Dose 100 g/week 200 g/week Once daily application Should not be used for longer than 2 consecutive weeks Should not be used for longer than 2 consecutive weeks Should not be used for longer Page 6 of 11

    CLINICAL POLICY Roflumilast Plaque Psoriasis
    Drug Name desoximetasone 0.05% (Topicort®) cream, ointment, gel fluocinolone acetonide 0.025% (Synalar®) cream, ointment fluticasone propionate 0.05% (Cutivate®) cream Dosing Regimen Dose Limit/ Maximum Dose than 2 consecutive weeks mometasone furoate 0.1% (Elocon®) cream, lotion, ointment triamcinolone acetonide 0.1%, 0.25%,0.5% (Aristocort®, Kenalog®) cream, ointment Combination Corticosteroid + (Vitamin D Analog or Retinoid) Enstilar® (calcipotriene 0.005% and betamethasone dipropionate 0.064%) foam Apply topically to affected areas QD for up to 4 weeks. Avoid use on face, groin, axillae, skin treatment site with atrophy present, or with occlusive dressing unless directed by a healthcare provider Apply a thin layer of lotion once daily to affected areas until control is achieved
    Apply twice daily to psoriatic lesions of the face and intertriginous areas Apply twice daily to affected intertriginous areas Dosing Regimen Duobrii® (halobetasol propionate 0.01% and tazarotene 0.045%) lotion Topical Calcineurin Inhibitors tacrolimus (Protopic®) (off-label) pimecrolimus (Elidel®) (off-label) Seborrheic Dermatitis Drug Name Refer to prescribing information Topical Antifungal
    ketoconazole (Nizoral® A-D, Extina®, Ketodan®, Xolegel™) 1-2% shampoo, 1- 2% cream, foam, gel ciclopirox 1-1.5% shampoo, 0.77% gel, 1% cream miconazole 2% solution Page 7 of 11 60 g/4 days
    50 g/week 2 applications/day 2 applications/day
    Dose Limit/ Maximum Dose Refer to prescribing information

    CLINICAL POLICY Roflumilast Plaque Psoriasis
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Refer to prescribing information clotrimazole (Lotrimin®) 1% cream, ointment, solution econazole (Ecoza®) 1% cream, foam
    luliconazole (Luzu®) 1% cream oxiconazole (Oxistat®) 1% cream, lotion sulconazole (Exelderm®) 1% cream, solution Topical Corticosteroids betamethasone dipropionate 0.05% cream, gel, lotion, spray; betamethasone valerate 0.12% foam, 0.1% cream, lotion clobetasol propionate (Temovate®, Temovate E®) 0.05% cream, ointment, gel, solution, shampoo desonide (Desowen®, Tridesilon®, Verdeso®) 0.05% cream, foam, gel, lotion, ointment hydrocortisone (NuZon®, NuCort®) 0.5-2.5% cream, ointment, lotion fluocinolone (Synalar®) 0.01% shampoo, lotion, 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. *Off-label Refer to prescribing information Appendix C: Contraindications/Boxed Warnings • Contraindication(s): moderate to severe liver impairment (Child-Pugh B or C) • Boxed warning(s): none reported V. Dosage and Administration
    Drug Name Daliresp Indication Dosing Regimen COPD 500 mcg PO QD (starting treatment with 250 mcg QD for 4 weeks and increasing to 500 Maximum Dose 500 mcg/day Page 8 of 11

    CLINICAL POLICY Roflumilast Drug Name Zoryve Indication Dosing Regimen mcg QD thereafter may reduce the rate of discontinuation in some patients) Apply cream to affected areas once daily Apply foam to affected areas once daily Plaque psoriasis Seborrheic dermatitis Maximum Dose Once daily application Once daily application VI. Product Availability
    Drug Name Daliresp Zoryve Availability Tablets: 250 mcg, 500 mcg Cream (0.3%): 60 g tube Foam (0.3%): 60 g can VII.