Ibuprofen/Famotidine (Duexis) Form

Ibuprofen/famotidine (Duexis®) is a combination of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and famotidine, a histamine H2-receptor (H2RA) antagonist.
FDA Approved Indication(s) Duexis is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications.
Limitation(s) of use: The clinical trials primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer. Controlled trials do not extend beyond 6 months. 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 Duexis is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Rheumatoid Arthritis or Osteoarthritis (must meet all):

1. Prescribed to decrease the risk of developing NSAID-induced gastric ulcers in patients with rheumatoid arthritis or osteoarthritis;
2. Age ≥ 18 years;
   3. Failure of a H2RA antagonist (e.g., ranitidine) in combination with a NSAID (e.g., ibuprofen), unless contraindicated or clinically significant adverse effects are experienced;
3. Failure of three proton pump inhibitors (PPIs) (e.g., omeprazole, pantoprazole, lansoprazole) in combination with three different NSAIDs, unless clinically significant adverse effects are experienced or all are contraindicated;
4. Member must instead use the individual components (i.e., famotidine and ibuprofen) concurrently, unless contraindicated or clinically significant adverse effects are experienced;

5. Member has at least one of the following risk factors for developing NSAID-induced gastric ulcers (a, b, or c): a. Age > 65 years; Page 1 of 7

   CLINICAL POLICY Ibuprofen/Famotidine b. Member has a history of peptic ulcer disease; c. Concurrent use of antiplatelets, corticosteroids, or anticoagulants;

6. If request is for brand Duexis, member must use generic ibuprofen/famotidine, unless contraindicated or clinically significant adverse effects are experienced;
7. Dose does not exceed 2,400 mg ibuprofen/79.8 mg famotidine (3 tablets) per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
8. 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
9. 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. Rheumatoid Arthritis or Osteoarthritis (must meet all):
10. 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. Member continues to have at least one of the following risk factors for developing NSAID-induced gastric ulcers (a, b, or c): a. Age > 65 years; b. Member has a history of peptic ulcer disease; c. Concurrent use of antiplatelets, corticosteroids, or anticoagulants;

11. If request is for a dose increase, new dose does not exceed 2,400 mg ibuprofen/79.8 mg famotidine (3 tablets) per day. Approval duration: 6 months Page 2 of 7

    CLINICAL POLICY Ibuprofen/Famotidine B. Other diagnoses/indications (must meet 1 or 2):

12. 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

13. 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 GI: gastrointestinal H2RA: histamine H2-receptor antagonist NSAID: nonsteroidal anti-inflammatory drug PPI: proton pump inhibitor 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 PPIs lansoprazole (Prevacid) omeprazole (Prilosec) NSAID-induced ulcer prophylaxis: 15 mg PO QD
    30 mg/day (for most indications) NSAID-associated gastric ulcer (healing): 30 mg PO QD
    NSAID-induced ulcer prophylaxis†: 20 mg PO QD
    40 mg/day (for most indications) Page 3 of 7

    CLINICAL POLICY Ibuprofen/Famotidine Drug Name Dosing Regimen pantoprazole (Protonix) NSAID-induced ulcer prophylaxis†: 40 mg PO QD Dose Limit/ Maximum Dose 80 mg/day (for most GERD indications) Osteoarthritis: 150 mg/day Rheumatoid arthritis: 200 mg/day PO
    Ankylosing spondylitis 125 mg/day
    1,200 mg/day 3,200 mg/day 3,200 mg/day 200 mg/day 150 mg/day Osteoarthritis:
    50 mg PO BID-TID or 75 mg PO BID Rheumatoid arthritis:
    50 mg PO TID-QID, or 75 mg PO BID Ankylosing spondylitis:
    25 mg PO QID with an additional 25 mg dose at bedtime Osteoarthritis or rheumatoid arthritis: 400 – 500 mg PO BID 400 – 600 mg PO TID-QID 400 – 800 mg PO TID-QID 25 PO BID-TID 75 mg PO QD-BID 50 mg PO QID or 75 mg PO TID 7.5 mg – 15 mg PO QD 250 – 500 mg PO BID 275 – 550 mg PO BID 300 mg/day 15 mg/day 1,500 mg/day 1,650 mg/day 600 – 1200 mg PO QD 10 – 20 mg PO QD 1,500 mg PO BID or 1,000 mg PO TID 150 mg – 200 mg PO BID 400 – 600 mg PO TID 50 – 100 mg PO Q4-6hr 1,800 mg/day 20 mg/day 3,000 mg/day 400 mg/day 1,800 mg/day 400 mg/day 20 mg – 40 mg BID NSAIDs diclofenac (Voltaren)
    etodolac (Lodine) fenoprofen (Nalfon)
    ibuprofen (Motrin)
    indomethacin (Indocin) indomethacin SR (Indocin SR) ketoprofen (Orudis)
    meloxicam (Mobic)
    naproxen (Naprosyn)
    naproxen sodium (Anaprox, Anaprox DS) oxaprozin (Daypro) piroxicam (Feldene) salsalate (Disalcid) sulindac (Clinoril) tolmetin
    meclofenamate
    H2RA antagonists famotidine (Pepcid) Varies based on indication 300 mg/day (for most indications) 1,200 mg/day (for most indications) ranitidine (Zantac) 150 mg PO BID cimetidine (Tagamet) NSAID induced ulcer prophylaxis†: 200-400 mg PO QD 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 4 of 7

    CLINICAL POLICY Ibuprofen/Famotidine †Off-label indication Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to ibuprofen or famotidine; history of asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs; in the setting of coronary artery bypass graft (CABG) surgery; hypersensitivity to other H2-receptor antagonists • Boxed warning(s): NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke; NSAIDs cause an increased risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines; Duexis is contraindicated in the setting of CABG surgery V. Dosage and Administration
    Indication Rheumatoid arthritis or osteoarthritis Dosing Regimen One tablet PO TID
    Maximum Dose 2,400 mg ibuprofen/79.8 mg famotidine per day VI. Product Availability
    Tablet: 800 mg ibuprofen/26.6 mg famotidine VII.