ULORIC, Febuxostat Form

Febuxostat (Uloric®) is a xanthine oxidase inhibitor. FDA Approved Indication(s) Uloric is indicated for the chronic management of hyperuricemia in patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. Limitation(s) of use: Uloric is not recommended for the treatment of asymptomatic hyperuricemia.
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 Uloric is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hyperuricemia (must meet all):

1. Diagnosis of hyperuricemia associated with gout;
   2. Current (within the last 30 days) serum urate ≥ 6 mg/dL;
   3. Age ≥ 18 years;
   4. One of the following (a or b): a. Failure of combination urate-lowering therapy (allopurinol and probenecid OR allopurinol and probenecid-containing product) at up to maximally tolerated doses; b. Member has intolerance or contraindication to combination urate-lowering therapy, and failure of allopurinol or probenecid, at up to maximally tolerated doses, unless clinically significant adverse effects are experienced or both are contraindicated;
2. Member must use generic febuxostat, unless contraindicated or clinically significant adverse effects are experienced;

3. Uloric is not prescribed concurrently with azathioprine or mercaptopurine;

   7. Dose does not exceed any of the following (a or b): a. 80 mg per day; b. 1 tablet per day. Page 1 of 6

   CLINICAL POLICY Febuxostat Approval duration:
   HIM – 12 months Medicaid – Length of Benefit 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; 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 and CP.PMN.53 for Medicaid. II. Continued Therapy A. Hyperuricemia (must meet all):
5. 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);
6. Member must use generic febuxostat, unless contraindicated or clinically significant adverse effects are experienced;
7. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: a. Reduced frequency of gout attacks; b. Serum urate level < 6 mg/dL;
8. If request is for a dose increase, new dose does not exceed any of the following (a or b): a. 80 mg per day; b. 1 tablet per day. Approval duration:
   HIM – 12 months Medicaid – Length of Benefit 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): Page 2 of 6

   CLINICAL POLICY Febuxostat 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 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; 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 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 – 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 allopurinol (Zyloprim®) probenecid colchicine (Colcrys®, Mitigare®) probenecid/colchicine 100 mg PO QD; may be increased by 100 mg every 2 to 4 weeks until serum urate concentration is ≤ 6 mg/dL or until maximum of 800 mg/day is reached 250 mg PO BID for the first week, then 500 mg PO BID Prevention of gout flares:
      0.6 mg PO QD or BID
      1 tablet (probenecid 500 mg/ colchicine 0.5 mg) PO QD for 1 week, then 2 tablet PO BID Dose Limit/ Maximum Dose 800 mg/day 2 g/day Prevention of gout flares: 1.2 mg/day 4 tablets/day of probenecid/colchicine (each tablet with 500 mg of probenecid/0.5 mg colchicine) is the usual maximally tolerated dose
      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. Page 3 of 6

   CLINICAL POLICY Febuxostat Appendix C: Contraindications/Boxed Warnings • Contraindication(s): patients being treated with azathioprine or mercaptopurine • Boxed warning(s): Cardiovascular death Appendix D: General Information • In November 2017, the FDA MedWatch issued an alert to the public regarding the preliminary results from a safety clinical trial that showed an increased risk of heart- related death with febuxostat compared to allopurinol. The febuxostat drug labels already carried a Warning and Precaution about cardiovascular events because the clinical trials conducted before approval showed a higher rate of heart-related problems in patients treated with febuxostat compared to allopurinol. These problems included heart attacks, strokes, and heart-related deaths. As a result, the FDA required an additional safety clinical trial after the drug was approved and on the market to better understand these differences, and that trial result continued to show increased heart-related death with febuxostat. • Per 2020 ACR guidelines, the minimum threshold for all patients on urate-lowering therapy is < 6.8 mg/dL. For patients with non-palpable, non-tophaceous disease in long- term clinical remission (for several years) and whose serum urate level is < 6.8 mg/dL, there is not a need for drug therapy to be up titrated for the sole purpose of reaching a goal of serum urate < 6 mg/dL. However, for all other patients with gout and recent symptoms of gout or tophi, the recommended target goal is a serum urate level < 6 mg/dL. V. Dosage and Administration
   Indication Hyperuricemia in patients with gout Dosing Regimen 40 mg or 80 mg PO QD Maximum Dose 80 mg/day VI. Product Availability
   Tablets: 40 mg, 80 mg VII.