CELEBREX, Celecoxib Form

Celecoxib (Celebrex®, Elyxyb™) is a nonsteroidal anti-inflammatory drug (NSAID). FDA Approved Indication(s) Celebrex is indicated for the treatment of: • Osteoarthritis • Rheumatoid arthritis • Juvenile rheumatoid arthritis in patients 2 years and older • Ankylosing spondylitis • Acute pain • Primary dysmenorrhea Elyxyb is indicated for the acute treatment of migraine with or without aura in adults. Limitation of use: Elyxyb is not indicated for the preventive treatment of migraine.
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 Celebrex and Elyxyb are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Migraine Treatment (must meet all):

1. Request is for Elyxb;

   2. Diagnosis of migraine;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a, b, c, d, or e): a. Age > 65 years; b. Current use of a corticosteroid; c. Current use of an anticoagulant or antiplatelet (e.g., aspirin, warfarin, low molecular weight heparin, direct thrombin inhibitors, factor Xa inhibitors, clopidogrel); d. Prior gastrointestinal bleed or active peptic ulcer disease (not gastroesophageal reflux disease [GERD]); Page 1 of 9

   CLINICAL POLICY Celecoxib
   e. Failure of a ≥ 4 week trial of both of the following (i and ii), up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: i. Meloxicam; ii. One additional generic NSAID;

   5. Dose does not exceed 120 mg (4.8 mL) per day. Approval duration:
      Medicaid/HIM – 12 months
      Commercial – Length of Benefit B. All Other Indications – FOR MEDICAID and California COMMERCIAL ONLY (must meet all): Refer to Step Therapy policy HIM.PA.109 for HIM, CP.CPA.83 for Oregon Commercial
   6. Request is for Celebrex;
   7. Age ≥ 2 years;
   8. For brand Celebrex requests, member must use generic celecoxib, unless contraindicated or clinically significant adverse effects are experienced;
2. Member meets one of the following (a, b, c, d, or e): a. Age > 65 years; b. Current use of a corticosteroid; c. Current use of an anticoagulant or antiplatelet (e.g., aspirin, warfarin, low molecular weight heparin, direct thrombin inhibitors, factor Xa inhibitors, clopidogrel); d. Prior gastrointestinal bleed or active peptic ulcer disease (not gastroesophageal reflux disease [GERD]); e. Failure of a ≥ 4 week trial of both of the following (i and ii), up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: i. Meloxicam; ii. One additional generic NSAID;
3. Dose does not exceed both of the following (a and b):
   a. 800 mg per day; b. 2 capsules per day.
   Approval duration:
   Medicaid – 12 months
   Commercial – Length of Benefit C. 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: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or Page 2 of 9

   CLINICAL POLICY Celecoxib
   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

5. 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. Acute Migraine Treatment (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; 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. If request is for a dose increase, new dose does not exceed 120 mg (4.8 mL) per day. Approval duration:
      Medicaid/HIM – 12 months
      Commercial – Length of Benefit B. All Other Indications – FOR MEDICAID and COMMERCIAL ONLY (must meet all): Refer to Step Therapy policy HIM.PA.109 for HIM
   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);
   5. Member is responding positively to therapy;
   6. If request is for a dose increase, new dose does not exceed both of the following (i and ii):
      a. 800 mg per day; b. 2 capsules per day.
      Approval duration:
      Medicaid – 12 months
      Commercial – Length of Benefit 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): Page 3 of 9

   CLINICAL POLICY Celecoxib
   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

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: 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 CABG: coronary artery bypass graft FDA: Food and Drug Administration GERD: gastroesophageal reflux disease NSAID: nonsteroidal anti-inflammatory drug 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 naproxen sodium (Anaprox®, Anaprox DS®) sulindac (Clinoril®) salsalate (Disalcid®) piroxicam (Feldene®) indomethacin (Indocin®) indomethacin SR (Indocin® SR) meclofenamate (Meclomen®) meloxicam (Mobic®) ibuprofen (Motrin®) fenoprofen (Nalfon®) naproxen (Naprosyn®) Dose Limit/ Maximum Dose 1,650 mg/day 275 – 550 mg PO BID 150 – 200 mg PO BID 500 – 750 mg PO TID, titrated up to 3,000 mg/day 10 – 20 mg PO QD 25 – 50 mg PO BID -TID 75 mg PO QD - BID 400 mg/day 3,000 mg/day 20 mg/day 200 mg/day 150 mg/day 50 – 100 mg PO Q4-6hr 400 mg/day 7.5 – 15 mg PO QD 400 – 800 mg PO Q6-8hr 200 mg PO Q4-6hr 250 – 500 mg PO BID 15 mg/day 3,200 mg/day 3,200 mg/day 1,500 mg/day Page 4 of 9

   CLINICAL POLICY Celecoxib
   Drug Name Dosing Regimen Dose Limit/ Maximum Dose 300 mg/day 2,000 mg/day 1,800 mg/day ketoprofen (Orudis®) nabumetone (Relafen®) tolmetin (Tolmetin® DS) 25 – 75 mg PO Q6-8hr 1000 mg PO QD or 500 mg PO BID 400 mg PO TID, titrated up to 1800 mg/day 50 mg PO Q6-8hr diclofenac sodium (Voltaren®) oxaprozin (Daypro®) etodolac (Lodine®) 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. 600 – 1,200 mg PO QD 400 – 500 mg PO BID 1,800 mg/day 1,200 mg/day 200 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to celecoxib or any components of the drug product; history of asthma, urticaria, or other allergic-type reactions to aspirin or other NSAIDs; in the setting of coronary artery bypass graft (CABG) surgery; allergic-type reactions to sulfonamides • Boxed warning(s): increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke; increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines; in the setting of CABG surgery Appendix D: General Information
   • The risk vs. benefit of COX-II therapy should be individualized based on patient's previous GI history, other co-morbid conditions (e.g., angina, ischemic heart disease, myocardial infarction (MI), coronary artery disease, stroke), age, concurrent medications (e.g., warfarin, oral corticosteroids), duration and dose. • Celebrex has been associated with an increased risk of serious adverse cardiovascular (CV) events in a long-term placebo-controlled trial. Based on the currently available data, FDA has concluded that an increased risk of serious adverse CV events appears to be a class effect of NSAIDs. FDA has requested that the package insert for all NSAIDs, including Celebrex, be revised to include a boxed warning to highlight the potential increased risk of CV events and the well described risk of serious, and potentially life- threatening, gastrointestinal bleeding. V. Dosage and Administration
   Drug Name Indication Dosing Regimen Celecoxib (Celebrex) Osteoarthritis Rheumatoid arthritis 200 mg PO QD or 100 mg PO BID 100 to 200 mg PO BID Maximum Dose 800 mg/day 800 mg/day Page 5 of 9

   CLINICAL POLICY Celecoxib
   Drug Name Indication Dosing Regimen Juvenile rheumatoid arthritis Ankylosing spondylitis Acute pain or Primary dysmenorrhea Migraine 10-25 kg: 50 mg PO BID

   25 kg: 100 mg PO BID 200 mg PO QD or 100 mg PO BID. If no effect is observed after 6 weeks, a trial of 400 mg (single or divided doses) may be of benefit. 400 mg PO initially, followed by a 200 mg dose if needed on the first day. On subsequent days, 200 mg PO BID as needed 120 mg PO PRN. Use the fewest number of days per month, as needed. Celecoxib (Elyxyb) Maximum Dose 200 mg/day 800 mg/day 800 mg/day 120 mg/day VI. Product Availability
   Drug Name Celecoxib (Celebrex) Celecoxib (Elyxyb) Availability Capsules: 50 mg, 100 mg, 200 mg, and 400 mg Oral solution: 120 mg/4.8 mL (25 mg/mL) VII. References

   1. Celebrex Prescribing Information. New York, NY: G.D. Searle, LLC; May 2019. Available at: http://www.celebrex.com/. Accessed January 31, 2023.

9. Elyxyb Prescribing Information. Hyderabad, Telangana India: Dr. Reddy’s Laboratories Limited; August 2021. Available at: www.elyxyb.com. Accessed January 31, 2023.
   3. Lanza FL, Chan FK, Quigley EM et al. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009 Mar;104(3):728-38. doi: 10.1038/ajg.2009.115. Epub 2009 Feb 24.
10. Kolasinski SL, Neogi T, Hochberg MC et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis & Rheumatology. 2020 Feb; 72(2): 220-233.
11. Fraenkel L, Bathon JM, England BR et al. 2021American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care & Research. 2021 July; 73(7):924-939.
12. Onel KB, Horton DB, Lovell DJ et al. 2021 American College of Rheumatology guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for oligoarthritis, temporomandibular join arthritis, and systemic juvenile idiopathic arthritis. Arthritis & Rhematology. 2022 April; 74(4):553-569.

13. Ringold S, Weiss PF, Beukelman T et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013 Oct;65(10):2499-512. doi: 10.1002/art.38092. Page 6 of 9

    CLINICAL POLICY Celecoxib

14. Ringod S, Angeles-Han ST, Beukelman T et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the treatment of idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis Care & Research. 2019 June; 71(6): 717-734. doi: 10.1002/acr.23870.
15. Ware MM, Deodhar A, Akl EA et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2016 Feb;68(2):282-98. doi: 10.1002/art.39298.
16. Yeomans ND. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1998;338:727-734.
17. Silverstein, et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal antiinflammatory drugs for osteoarthritis and rheumatoid arthritis (CLASS Study). JAMA 2000;284:1247- 1255.
18. Mukherjee, et al. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-959.
19. Juni, et al. Are selective COX 2 inhibitors superior to traditional non-steroidal anti- inflammatory drugs. BMJ 2002;324:1287-1288.
20. Solomon DH, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004;109(17):2068-2073.
21. Ailani J, Burch RC, Robbins MS et al. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache 2021;61:1021-1039.
    Reviews, Revisions, and Approvals 2Q 2019 annual review: no significant changes.