Ulcer Therapy Combinations Form

The following are ulcer therapy products that require prior authorization: • Bismuth subcitrate potassium/metronidazole/tetracycline hydrochloride (Pylera®) • Omeprazole/clarithromycin/amoxicillin (Omeclamox-Pak®) • Rifabutin/omeprazole/amoxicillin (Talicia®) • Vonoprazan (Voquezna®) • Vonoprazan/amoxicillin/clarithromycin (Voquezna™ Triple Pak™) • Vonoprazan/amoxicillin (Voquezna™ Dual Pak™) FDA Approved Indication(s) • Pylera is indicated for use, in combination with omeprazole, for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori.
• Talicia, Voquezna (in combination with amoxicillin, or with amoxicillin and clarithromycin), Voquezna Triple Pak, and Voquezna Dual Pak are indicated for the treatment of Helicobacter pylori infection in adults.
• Omeclamox-Pak is indicated for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or up to one-year history) to eradicate H. pylori.* • Voquezna is additionally indicated: o For healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.
o To maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.
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• To reduce the development of drug-resistant bacteria and maintain the effectiveness of Pylera, Talicia, Omeclamox-Pak, Voquenza, Voquezna Triple/Dual Pak, and other antibacterial drugs, these products should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. 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 Omeclamox-Pak, Pylera, Talicia, Voquezna, Voquezna Triple Pak, and Voquezna Dual Pak are medically necessary when the following criteria are met:
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  CLINICAL POLICY Ulcer Therapy Products
  I. Initial Approval Criteria
  A. Helicobacter pylori Infection (must meet all):

  1. Diagnosis of H. pylori infection;
  2. Prescribed by or in consultation with a gastroenterologist or infectious disease specialist;
  3. Age ≥ 18 years;
  4. One of the following (a or b): a. For Omeclamox-Pak, Pylera, and Talicia requests, one of the following (i or ii): i. Member must instead use the individual components concurrently (i.e., for Talicia generic rifabutin, amoxicillin, omeprazole), unless contraindicated or clinically significant adverse effects are experienced; ii. Member must use generic Prevpac (lansoprazole, amoxicillin, clarithromycin), unless contraindicated or clinically significant adverse effects are experienced; b. For Voquezna and Voquezna Triple/Dual Pak requests, one of the following (i or ii): i. If H. pylori is clarithromycin- and amoxicillin-sensitive, member must use one of the following, unless clinically significant adverse effects are experienced or both regimens are contraindicated (1 or 2): 1) Generic Prevpac (lansoprazole, amoxicillin, clarithromycin); 2) Bismuth quadruple therapy; ii. If H. pylori is clarithromycin- or amoxicillin-resistant, member must use bismuth quadruple therapy, unless contraindicated or clinically significant adverse effects are experienced;
  5. For Pylera requests, prescribed in combination with a proton pump inhibitor (PPI; e.g., omeprazole);
  6. Dose does not exceed one of the following (a, b, c, d, e, or f): a. Omeclamox-Pak: two omeprazole capsules, two clarithromycin tablets, and four amoxicillin capsules per day for 10 days; b. Pylera: 12 capsules per day for 10 days; c. Talicia: 12 capsules per day for 14 days; d. Voquezna Triple Pak: two vonoprazan tablets, four amoxicillin capsules, and two clarithromycin tablets per day for 14 days; e. Voquezna Dual Pak: two vonoprazan tablets and six amoxicillin capsules per day for 14 days; f. Voquezna (i and ii):
     i. 40 mg per day for 14 days, in combination with amoxicillin with or without clarithromycin; ii. 2 tablets per day for 14 days. Approval duration:
     Omeclamox-Pak, Pylera – 10 days
     Talicia, Voquezna, Voquezna Triple/Dual Pak – 14 days B. Erosive Esophagitis (must meet all):
  7. Request is for Voquezna;
  8. Diagnosis of erosive esophagitis;
  9. Age ≥ 18 years; Page 2 of 9

  CLINICAL POLICY Ulcer Therapy Products

  4. Failure of ≥ 8 week trial of a PPI at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;
  5. Dose does not exceed the following (a and b): a. One of the following (i or ii): i. For the healing of erosive esophagitis: 20 mg per day for 8 weeks; ii. For the maintenance of erosive esophagitis: 10 mg per day for 6 months; b. 1 tablet per day. Approval duration: Up to 8 months
     C. Other diagnoses/indications (must meet 1 or 2):
  6. 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
  7. 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. Helicobacter pylori Infection, Erosive Esophagitis
  8. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable 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): 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
  10. 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 Page 3 of 9

  CLINICAL POLICY Ulcer Therapy Products
  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, CP.PMN.53 for Medicaid, and HIM.PA.154 for health insurance marketplace, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration 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.
  Dosing Regimen Drug Name clarithromycin triple regimen bismuth quadruple regimen concomitant regimen sequential regimen H. pylori infection: 14 days: PPI (standard or double dose) BID; Clarithromycin 500 mg BID; Amoxicillin 1,000 mg BID or metronidazole 500 mg TID (if penicillin allergy) H. pylori infection: 10-14 days: PPI (standard dose) BID; bismuth subcitrate (120- 300 mg) or subsalicylate (300 mg) QID; tetracycline 500 mg QID; metronidazole 250 mg QID or 500 mg TID-QID H. pylori infection: 10-14 days: PPI (standard dose) BID; Clarithromycin 500 mg BID; Amoxicillin 1,000 mg BID; Metronidazole or tinidazole 500 mg BID H. pylori infection: 5-7 days of BID PPI (standard dose) + amoxicillin 1,000 mg BID; followed by 5-7 days of BID PPI, clarithromycin 500 mg BID + metronidazole/tinidazole 500 mg BID hybrid regimen H. pylori infection: 7 days of BID PPI (standard dose) + amoxicillin 1,000 mg BID; followed by 7 days of BID PPI, Page 4 of 9 Dose Limit/ Maximum Dose See dosing regimen See dosing regimen See dosing regimen See dosing regimen See dosing regimen

  CLINICAL POLICY Ulcer Therapy Products
  Drug Name Dosing Regimen levofloxacin triple regimen amoxicillin 1,000 mg BID + clarithromycin 500 mg BID + metronidazole/tinidazole 500 mg BID H. pylori infection: 10-14 days: PPI (standard dose) BID; levofloxacin 500 mg QD; amoxicillin 1,000 mg BID H. pylori infection: 5-7 days of BID PPI (standard dose) + amoxicillin 1,000 mg BID; followed by 5-7 days of BID PPI, amoxicillin 1,000 mg BID + metronidazole/tinidazole 500 mg BID + QD levofloxacin 500 mg rifabutin triple H. pylori infection: levofloxacin sequential regimen Dose Limit/ Maximum Dose See dosing regimen See dosing regimen See dosing regimen 10 days of BID PPI (standard dose) + amoxicillin 1,000 mg BID + rifabutin 300 mg QD Erosive Esophagitis Varies PPIs: lansoprazole, omeprazole, pantoprazole, rabeprazole, esomeprazole 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. Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
  o Omeclamox-Pak: known hypersensitivity to omeprazole, any macrolide antibiotic, any penicillin, or any component of the formulations, coadministration with pimozide, ergotamine or dihydroergotamine o Pylera: concurrent usage of methoxyflurane, disulfiram usage within the last two weeks, alcoholic beverage consumption for at least three days during or after therapy, patients with Cockayne syndrome, severe renal impairment, women who are pregnant, known hypersensitivity to product components o Talicia: hypersensitivity to the components of Talicia; patients receiving rilpivirine- containing products, delavirdine or voriconazole o Voquezna: known hypersensitivity to vonoprazan or any component of Voquezna; rilpivirine-containing products
  o Voquezna Triple Pak: known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams, clarithromycin or any other macrolide antimicrobial, or any component of Voquezna Triple Pak; rilpivirine-containing products; due to clarithromycin component: pimozide, lomitapide, lovastatin, simvastatin, ergot alkaloids (ergotamine or dihydroergotamine), colchicine in renal or hepatic impairment, history of cholestatic jaundice/hepatic dysfunction with use of clarithromycin, lurasidone Page 5 of 9

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  o Voquezna Dual Pak: known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams, or any component of Voquezna Dual Pak; rilpivirine-containing products
  • Boxed warning(s):
  o Pylera: potential for carcinogenicity (metronidazole has been shown to be carcinogenic in mice and rats) V. Dosage and Administration
  Drug Name Indication Dosing Regimen Omeprazole/ clarithromycin/amoxicillin (Omeclamox-Pak) H. pylori Bismuth subcitrate potassium/ metronidazole/tetracycline hydrochloride (Pylera) Rifabutin/omeprazole/amo xicillin (Talicia) Vonoprazan/amoxicillin/ clarithromycin (Voquezna Triple Pak) H. pylori H. pylori H. pylori Vonoprazan/amoxicillin (Voquezna Dual Pak) H. pylori Vonoprazan (Voquezna) H. pylori Erosive esophagitis omeprazole 20 mg plus clarithromycin 500 mg plus amoxicillin 1,000 mg, each given PO BID for 10 days Three capsules PO QID for 10 days with omeprazole 20 mg BID Four capsules PO Q8H for 14 days Each of the following given BID for 14 days: vonoprazan 20 mg (2 tablets/day), amoxicillin 1,000 mg (4 capsules/day), and clarithromycin 500 mg (2 tablets/day)
  Vonoprazan 20 mg BID (2 tablets/day) and amoxicillin 1,000 mg TID a day (6 capsules/day) for 14 days Dual therapy: 20 mg PO BID in combination with amoxicillin 1,000 mg PO TID for 14 days Triple therapy: 20 mg PO BID in combination with amoxicillin 1,000 mg and clarithromycin 500 mg PO BID for 14 days Healing: 20 mg PO QD for 8 weeks Maintenance: 10 mg PO QD for up to 6 months Maximum Dose See regimen See regimen See regimen See regimen See regimen 20 mg/day for 14 days See regimen Page 6 of 9

  CLINICAL POLICY Ulcer Therapy Products
  VI. Product Availability
  Drug Name Omeprazole/clarithromycin/ amoxicillin (Omeclamox-Pak) Bismuth subcitrate potassium/ metronidazole/tetracycline hydrochloride (Pylera) Rifabutin/omeprazole/ amoxicillin (Talicia) Vonoprazan/amoxicillin/ clarithromycin (Voquezna Triple Pak) Vonoprazan/amoxicillin (Voquezna Dual Pak) Vonoprazan (Voquenza) Availability Pack of 10 daily administration cards for morning and evening dosing, each containing: • Two 20 mg omeprazole delayed-release capsules • Two 500 mg clarithromycin tablets • Four 500 mg amoxicillin capsules
  Each capsule contains: 140 mg of bismuth subcitrate potassium, 125 mg metronidazole, 125 mg of tetracycline hydrochloride Delayed-release capsule: omeprazole 10 mg, (equivalent to 10.3 mg of omeprazole magnesium), amoxicillin 250 mg, and rifabutin 12.5 mg Carton of 14 daily administration packs for morning and evening dosing, each containing the following three drug products: tablets: vonoprazan 20 mg, clarithromycin 500 mg; capsules: amoxicillin 500 mg Carton of 14 daily administration packs for morning, mid- day and evening dosing, each containing the following two drug products: tablets: vonoprazan 20 mg; capsules: amoxicillin 500 mg Tablets: 10 mg, 20 mg VII.