TOLAK, Fluorouracil (Topical) Form

Fluorouracil (Tolak® Cream, 4%) is a nucleoside metabolic inhibitor.
FDA Approved Indication(s) Tolak is indicated for the topical treatment of actinic keratosis lesions of the face, ears, and/or scalp. 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 Tolak is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Actinic Keratosis (must meet all):

1. Diagnosis of actinic keratosis of the face, ears, or scalp;
   2. Member must use fluorouracil 5% topical cream, unless contraindicated or clinically significant adverse effects are experienced;
   3. Dose does not exceed once daily application. Approval duration: 4 weeks B. Other diagnoses/indications (must meet 1 or 2):
2. 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

3. 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 Page 1 of 5

   CLINICAL POLICY Fluorouracil Cream of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Actinic Keratosis (must meet all):

4. 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. Tolak therapy for the current requested use has not exceeded 4 weeks;
   4. If request is for a dose increase, new dose does not exceed once daily application. Approval duration: Up to 4 weeks total per treatment course 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.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 DPD: dihydropyrimidine dehydrogenase deficiency FDA: Food and Drug Administration Page 2 of 5

   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.
   Dosing Regimen Drug Name Actinic Keratosis: Apply to lesions topically BID for 2 to 6 weeks fluorouracil 5% topical cream (Efudex®) 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. Dose Limit/ Maximum Dose Varies Appendix C: Contraindications/Boxed Warnings • Contraindications: dihydropyrimidine dehydrogenase (DPD) deficiency, pregnancy • Boxed warning(s): none reported V. Dosage and Administration
   Indication Actinic keratosis lesions Dosing Regimen Apply topically QD for 4 weeks in an amount sufficient to cover the lesions with a thin film, massaging uniformly into the skin Maximum Dose As specified VI. Product Availability
   Topical cream (4%): 40 g VII.