Naproxen/Esomeprazole (Vimovo) Form

Naproxen/esomeprazole magnesium (Vimovo®) is a fixed combination of naproxen, a non- steroidal anti-inflammatory drug (NSAID), and esomeprazole, a proton pump inhibitor (PPI).
FDA Approved Indication(s) Vimovo is indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric ulcers. The naproxen component of Vimovo is indicated for relief of signs and symptoms of: • Osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults. • Juvenile idiopathic arthritis (JIA) in adolescent patients. The esomeprazole magnesium component of Vimovo is indicated to decrease the risk of developing naproxen-associated gastric ulcers. Limitation(s) of use:
• Do not substitute Vimovo with the single-ingredient products of naproxen and esomeprazole magnesium. • Vimovo is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. • Controlled studies 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 Vimovo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. All FDA-Approved Indications (must meet all):

1. Prescribed to decrease the risk of developing NSAID-induced gastric ulcers in patients with rheumatoid arthritis, JIA, osteoarthritis, or ankylosing spondylitis;

2. Age ≥ 12 years;

   3. Weight ≥ 38 kg;
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   CLINICAL POLICY Naproxen/Esomeprazole

3. Failure of three 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., esomeprazole and naproxen) concurrently, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for esomeprazole.
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; b. Member has a history of peptic ulcer disease;
   c. Concurrent use of antiplatelets, corticosteroids, or anticoagulants;
6. If request is for brand Vimovo, member must use generic naproxen/esomeprazole, unless contraindicated or clinically significant adverse effects are experienced;
7. Dose does not exceed one of the following (a or b):
   a. For adults and adolescent patients weighting ≥ 50 kg, both of the following (i and ii):
   i. 1,000 mg naproxen/40 mg esomeprazole per day; ii. 2 tablets per day; b. For adolescent patients weighing 38 kg to < 50 kg, both of the following (i and ii):
   i. 750 mg naproxen/40 mg esomeprazole per day; ii. 2 tablets per day. Approval duration:
   Medicaid/HIM – 12 months
   Commercial – Length of Benefit 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. All FDA Approved Indications (must meet all):

   1. Member meets one of the following (a or b): Page 2 of 8

   CLINICAL POLICY Naproxen/Esomeprazole 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 has 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;
10. If request is for a dose increase, new dose does not exceed one of the following (a or b):
    a. For adults and adolescent patients weighing ≥ 50 kg, both of the following (i and ii):
    i. 1,000 mg naproxen/40 mg esomeprazole per day; ii. 2 tablets per day; b. For adolescent patients weighing 38 kg to < 50 kg, both of the following (i and ii):
    i. 750 mg naproxen/40 mg esomeprazole per day; ii. 2 tablets per day. Approval duration:
    Medicaid/HIM – 12 months Commercial – Length of Benefit B. Other diagnoses/indications (must meet 1 or 2):
11. 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

12. 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 – Page 3 of 8

    CLINICAL POLICY Naproxen/Esomeprazole 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 JIA: juvenile idiopathic arthritis 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) NSAID-induced ulcer prophylaxis: 15 mg PO QD
    30 mg/day (for most indications) omeprazole (Prilosec) pantoprazole (Protonix)
    NSAIDs diclofenac (Voltaren)
    etodolac (Lodine) fenoprofen (Nalfon)
    ibuprofen (Motrin)
    NSAID-associated gastric ulcer (healing): 30 mg PO QD
    NSAID-induced ulcer prophylaxis†: 20 mg PO QD
    NSAID-induced ulcer prophylaxis†: 40 mg PO QD 40 mg/day (for most indications) 40 mg/day (for most GERD indications) Osteoarthritis:
    50 mg PO BID-TID or 75 mg PO BID Osteoarthritis:
    150 mg/day Rheumatoid arthritis: 200 mg/day
    Ankylosing spondylitis 125 mg/day
    1200 mg/day 3,200 mg/day 3,200 mg/day 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 Page 4 of 8

    CLINICAL POLICY Naproxen/Esomeprazole Drug Name Dosing Regimen 25 PO BID-TID 75 mg PO QD-BID Dose Limit/ Maximum Dose 200 mg/day 150 mg/day 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 indomethacin (Indocin) indomethacin SR (Indocin SR) ketoprofen (Orudis)
    meloxicam (Mobic)
    naproxen (Naprosyn)
    naproxen sodium (Anaprox, Anaprox DS) oxaprozin (Daypro) piroxicam (Feldene) salsalate (Disalcid) 1,800 mg/day 20 mg/day 3,000 mg/day 600 – 1,200 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 sulindac (Clinoril) tolmetin
    meclofenamate
    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. †Off-label indication 400 mg/day 1,800 mg/day 400 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product including omeprazole; history of asthma, urticaria, or other allergic-type reactions to aspirin or other NSAIDs; in the setting of coronary artery bypass graft (CABG) surgery; concurrent use of rilpivirine- containing products • Boxed warning(s): NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal; NSAIDs, including naproxen, cause an increased risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines; Vimovo is contraindicated in the setting of CABG surgery V. Dosage and Administration
    Indication Rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis Juvenile idiopathic arthritis in adolescent patients 12 years of age and Dosing Regimen One tablet PO BID of either 375 mg naproxen/20 mg esomeprazole or 500 mg naproxen/20 mg esomeprazole Maximum Dose 1,000 mg naproxen/40mg esomeprazole per day

    50 kg: One tablet PO BID of either 375 mg naproxen/20 mg esomeprazole or 500 mg naproxen/20 mg esomeprazole 50 kg: 1,000 mg naproxen/40mg esomeprazole per day Page 5 of 8

    CLINICAL POLICY Naproxen/Esomeprazole Indication older and weighing at least 38 kg Dosing Regimen 38 kg to < 50 kg: 375 mg naproxen/20 mg esomeprazole PO BID Maximum Dose 38 kg to 50 kg: 750 mg naproxen/40 mg esomeprazole per day VI. Product Availability
    Delayed-release tablets (enteric-coated naproxen/immediate-release esomeprazole):
    375 mg/20 mg, 500 mg/20 mg
    VII. References

    1. Vimovo Prescribing Information. Lake Forest, IL: Horizon Pharma USA, Inc.; April 2021. www.vimovo.com. Accessed January 31, 2023.
13. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. January 31, 2023.
14. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2021. Available at: http://www.clinicalpharmacology-ip.com/. January 31, 2023.
    Reviews, Revisions, and Approvals 2Q 2019 annual review: no significant changes.