ZONALON, Doxepin HCl (Antipruritic) PRUDOXIN, Doxepin HCl (Antipruritic) SILENOR, Doxepin HCl (Sleep) Form

Doxepin (Silenor®, Prudoxin™, Zonalon®) is a tricyclic antidepressant. FDA Approved Indication(s) Silenor is indicated for treatment of insomnia characterized by difficulties with sleep maintenance. Prudoxin and Zonalon are indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus. 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 Silenor, Prudoxin, and Zonalon are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Insomnia (must meet all):

1. Diagnosis of insomnia;
2. Request is for doxepin tablets (Silenor);
3. Age ≥ 18 years;
4. Failure of two preferred or formulary agents indicated for insomnia (see Appendix B for examples) at maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;
   
   5. For brand Silenor requests, member must use doxepin tablets (generic Silenor), unless contraindicated or clinically significant adverse effects are experienced;
   6. Dose does not exceed 6 mg (1 tablet) per day. Approval duration: 6 months B. Pruritus (must meet all):
   7. Diagnosis of pruritus associated with conditions such as atopic dermatitis (eczema) or lichen simplex chronicus*;
   8. Request is for doxepin cream (Prudoxin, Zonalon);

5. Age ≥ 18 years; Page 1 of 7

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   4. Failure of ≥ 2 topical therapies (see Appendix B for examples) in the last 6 months, unless clinically significant adverse effects are experienced or all are contraindicated (if appropriate, at least one trial should include a topical corticosteroid);
   5. For brand Prudoxin or Zonalon requests, member must use generic doxepin cream, unless contraindicated or clinically significant adverse effects are experienced;
   6. Dose does not exceed topical application up to four times daily. Approval duration: 6 months (1 tube)
      __ *Lichen simplex chronicus is a secondary skin condition resulting from excessive scratching associated with a variety of conditions including atopic dermatitis. Complaints of intense pruritus are common.
      C. 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: HIM.PA.33 for health insurance marketplace; 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: HIM.PA.103 for health insurance marketplace; 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: HIM.PA.154 for health insurance marketplace.
      II. Continued Therapy A. Insomnia (must meet all):
   9. 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);
   10. Request is for doxepin tablets (Silenor);
6. Member is responding positively to therapy;

7. For brand Silenor requests, member must use doxepin tablets (generic Silenor), unless contraindicated or clinically significant adverse effects are experienced;

   5. If request is for a dose increase, new dose does not exceed 6 mg (1 tablet) per day. Approval duration: 12 months B. Pruritus (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; Page 2 of 7

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   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);

8. Request is for doxepin cream (Prudoxin, Zonalon);
9. Member is responding positively to therapy;
10. For brand Prudoxin or Zonalon requests, member must use generic doxepin cream, unless contraindicated or clinically significant adverse effects are experienced;
    5. Member has not received topical doxepin in the last 180 days;

11. If request is for a dose increase, new dose does not exceed topical application up to four times daily. Approval duration: 6 months (1 tube) C. 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: HIM.PA.33 for health insurance marketplace; 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: HIM.PA.103 for health insurance marketplace; 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: HIM.PA.154 for health insurance marketplace.
       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 – HIM.PA.154 for health insurance marketplace 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 Dose Limit/ Maximum Dose Insomnia estazolam eszopiclone (Lunesta®) 1 mg PO HS PRN Adults: 1 mg – 3 mg PO HS PRN Elderly: 1 mg - 2 mg PO HS PRN 2 mg/day Adults: 3 mg/day Elderly: 2 mg/day Page 3 of 7

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    Drug Name Dosing Regimen ramelteon (Rozerem®) temazepam (Restoril®) Adults: 8 mg PO HS PRN Adults: 15 – 30 mg PO HS PRN Elderly: 7.5 – 15 mg PO HS PRN 0.25 mg PO HS PRN 10 mg PO HS PRN triazolam (Halcion®) zaleplon (Sonata®) zolpidem CR (Ambien CR®) Adults: 6.25-12.5 mg PO HS PRN Elderly: 6.25 mg PO HS PRN 5 mg PO HS PRN desonide, 0.05% zolpidem IR (Ambien®) Pruritis clobetasol propionate, 0.05% Topical application up to two times daily Topical application up to two to four times daily depending on formulation Topical application up to three times daily Topical application up to four times daily halcinonide, 0.1% (Halog®) Dose Limit/ Maximum Dose 8 mg/day 30 mg/day 0.5 mg/day 20 mg/day 12.5 mg/day 10 mg/day Varies OTC topical diphenhydramine 1-2% (e.g., Anti-Itch® Maximum Strength, Anti-Itch®, Benadryl® Itch Stopping, Itch Relief®) 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines o Concomitant use with monoamine oxidase inhibitors (MAOIs) (Silenor only) o Patients with untreated narrow angle glaucoma or severe urinary retention • Boxed warning(s): none reported V. Dosage and Administration
    Indication Insomnia Drug Name Doxepin (Silenor) Doxepin (Prudoxin, Zonalon) Moderate pruritus
    Dosing Regimen Adults: 6 mg PO HS PRN Elderly: 3 mg PO HS PRN Apply to the affected area(s) topically 4 times daily allowing at least 3 to 4 hours between applications, for up to 8 days Maximum Dose 6 mg/day For up to 8 days VI. Product Availability
    Drug Name Doxepin (Silenor) Product Availability Tablets: 3 mg, 6 mg Page 4 of 7

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    Drug Name Doxepin (Prudoxin) Doxepin (Zonalon) Product Availability Cream, 5%: 45 g Cream, 5%: 30 g, 45 g VII.