Proton Pump Inhibitors Drug Class Prior Authorization Protocol Line of Business: Medi-Cal P&T Approval Date: November 15, 2017 Effective Date: January 1, 2018 This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutics Subcommittee. Drugs Requiring Prior Authorization Review: Aciphex Sprinkle (rabeprazole), Dexilant (dexlansoprazole), Nexium (esomeprazole granules), Prevacid SoluTab (lansoprazole disintegrating DR), Prilosec (omeprazole granule), Protonix (pantoprazole granule), Zegerid (omeprazole-sodium bicarbonate capsule, packet powder for suspension) Formulary Alternatives: esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole Policy/Criteria: A. Drugs: Dexilant (dexlansoprazole), Zegerid (omeprazole - sodium bicarbonate), Prevacid SoluTab (lansoprazole) Diagnosis: a. Barrett s esophagus b. Erosive esophagitis c. Gastroduodenal ulcer d. H. pylori infection e. Hypersecretory condition (e.g. Zollinger Ellison syndrome, Retained Gastric Antrum syndrome) f. NSAID associated gastric ulcer g. Symptomatic GERD Specialist: No restriction Criteria: a. ONE of the following: i. Failure or clinically significant adverse effects of each formulary PPI alternative (lansoprazole, omeprazole, pantoprazole, rabeprazole and esomeprazole)
ii. For patients with documented difficulty swallowing: Trial and failure of formulary omeprazole and lansoprazole capsules sprinkled on apple sauce or juice as directed. iii. For patients with tube feeding: Nexium granule packet and Protonix granule packet are the preferred PPI products. b. Requested dose and duration must be consistent with FDA package labeled recommendation or DrugDex compendia. Clinical Justifications: American College of Gastroenterology: Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease 2013 Management of GERD: An 8-week course of PPIs is the therapy of choice for symptom relief and healing of erosive esophagitis. There is no major difference in efficacy between the different PPIs. Traditional delayed release PPIs should be administered 30-60 minutes before meal for maximal ph control. Newer PPIs may offer dosing flexibility relative to meal timing. PPI therapy should be initiated at once a day dosing, before the first meal of the day. For patients with partial response to once daily therapy, tailored therapy with adjustment of dose timing and/or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and/or sleep disturbance. Non-responders to PPI should be referred for evaluation. In patients with partial response to PPI therapy, increasing the dose to twice daily therapy or switching to a different PPI may provide additional symptom relief. Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued and in patients with complications including erosive esophagitis and Barrett s esophagus. For patients who require long-term PPI therapy, it should be administered in the lowest effective dose, including on demand or intermittent therapy. Potential Risks Associated with PPIs: Switching PPIs can be considered in the setting of side effects. Patients with known osteoporosis can remain on PPI therapy. Concern for hip fractures and osteoporosis should not affect the decision to use PPI long-term except in patients with other risk factors for hip fracture. PPI therapy can be a risk factor for Clostridium difficile infection and should be used with care in patients at risk. Short-term PPI usage may increase the risk of community acquired pneumonia. The risk does not appear elevated in long-term users. PPI therapy does not need to be altered in concomitant clopidogrel users as clinical data does not support an increased risk for adverse cardiovascular events.
American College of Gastroenterology: Diagnosis and Management of Barrett s Esophagus 2015 Therapy: Chemoprevention: Patients with BE should receive once-daily PPI therapy. Routine use of twice-daily dosing is not recommended, unless necessitated because of poor control of reflux symptoms or esophagitis. o PPI therapy is common in patients with BE, in part because of the high proportion of those patients who also have symptomatic GERD. In these cases, the use of PPIs is substantiated by the need for symptom control, making consideration of chemoprevention secondary. o With respect to optimizing medical therapy, dosages of PPI beyond twice daily have not been demonstrated to have beneficial effect in patients with BE. We recommend once-daily PPI therapy for patients with BE unless GERD symptoms require twice daily for adequate symptom control. Aspirin or nonsteroidal anti-inflammatory drugs should not be routinely prescribed to patients with BE as an antineoplastic strategy. Similarly, other putative chemopreventive agents currently lack sufficient evidence and should not be administered routinely. American College of Gastroenterology: Treatment of Helicobacter Pylori Infection 2017 When to test for H.pylori infection: All patients tested positive for H. pylori infection should be offered treatments. Who should be tested for H. pylori infection: o Patients with active peptic ulcer disease (PUD), a past history of PUD (unless previous cure of H. pylori infection has been documented), low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, or a history of endoscopic resection of early gastric cancer (EGC) o Patients with dyspepsia who is undergoing upper endoscopy o Patients initiating chronic treatment with a non-steroidal anti-inflammatory drug (NSAID) o Patients with unexplained iron deficiency anemia despite an appropriate evaluation o Adults with idiopathic thrombocytopenic purpura (ITP) Who could be tested for H. pylori infection: o Patients with uninvestigated dyspepsia who are under the age of 60 years and without alarm features o Patients who are taking long-term, low-dose aspirin to reduce the risk of ulcer bleeding Who need not be tested for H. pylori infection: o Patients with typical symptoms of gastroesophageal reflux disease (GERD) who do not have a history of PUD o Routine testing for and treatment of H. pylori in asymptomatic individuals with a family history of gastric cancer or patients with lymphocytic gastritis, hyperplastic gastric polyps, and hyperemesis gravidarum
Recommended therapies for H. pylori infection: Previous antibiotic exposure(s) should be taken into consideration when choosing an H. pylori treatment regimen In regions where H. pylori clarithromycin resistance is known to be <15% and in patients with no previous history of macrolide exposure: o Clarithromycin triple therapy consisting of a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days is a recommended treatment. Bismuth quadruple therapy consisting of a PPI, bismuth, tetracycline, and a nitroimidazole for 10 14 days is a recommended first-line treatment option. o Particularly in patients with previous macrolide exposure or who are allergic to penicillin Concomitant therapy consisting of a PPI, clarithromycin, amoxicillin and a nitroimidazole for 10 14 days is a recommended first-line treatment option Sequential therapy consisting of a PPI and amoxicillin for 5 7 days followed by a PPI, clarithromycin, and a nitroimidazole for 5 7 days is a suggested first-line treatment option Hybrid therapy consisting of a PPI and amoxicillin for 7 days followed by a PPI, amoxicillin, clarithromycin and a nitroimidazole for 7 days is a suggested first-line treatment option Levofloxacin triple therapy consisting of a PPI, levofloxacin, and amoxicillin for 10 14 days is a suggested first-line treatment option Fluoroquinolone sequential therapy consisting of a PPI and amoxicillin for 5 7 days followed by a PPI, fluoroquinolone, and nitroimidazole for 5 7 days is a suggested firstline treatment option Post-treatment recommendation: Whenever H. pylori infection is identified and treated, testing to prove eradication should be performed using a urea breath test, fecal antigen test or biopsy-based testing at least 4 weeks after the completion of antibiotic therapy and after PPI therapy has been withheld for 1 2 weeks. Salvage therapy recommendations: Avoid antibiotics that have been previously taken by the patient Bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options if a patient received a first-line treatment containing clarithromycin Clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options, if a patient received first-line bismuth quadruple therapy. Recommended salvage treatment regimens: o Bismuth quadruple therapy for 14 days. o Levofloxacin triple regimen for 14 days. o Concomitant therapy for 10 14 days. Suggested salvage treatment regimens: o Rifabutin triple regimen consisting of a PPI, amoxicillin, and rifabutin for 10 days. o High-dose dual therapy consisting of a PPI and amoxicillin for 14 days.
Clarithromycin triple therapy should be avoided as a salvage regimen. Most patients with a history of penicillin allergy do not have true penicillin hypersensitivity. After failure of first-line therapy, such patients should be considered for referral for allergy testing since the vast majority can ultimately be safely given amoxicillin-containing salvage regimens Therapy Comparison by Indications: Clinical Indications & Dosages Erosive Esophagitis associated with GERD Dexlansoprazole Treatment: 60mg once daily for 8 weeks Maintenance: 30mg once daily for up to 6 months Esomeprazole Treatment: 20-40mg once daily for 4-8 weeks Maintenance: 20mg once daily Lansoprazole Treatment: 30mg once daily for 8-16 weeks (another 8 weeks for recurrence may be considered) Maintenance: 15 mg once daily for up to 12 months Omeprazole Treatment: 20mg once daily for 4-8 weeks (additional 4-8 weeks may be considered) Maintenance: 20mg once daily Omeprazole-sodium Treatment: 20mg daily for 4-8 weeks (additional 4 weeks may be bicarbonate considered) Maintenance: 20mg once daily Pantoprazole Treatment: 40mg once daily for 8 weeks (additional 8 weeks may be considered) Maintenance: 40mg once daily Rabeprazole Treatment: 20mg once daily for 4-8 weeks Maintenance: 20mg once daily Symptomatic GERD Dexlansoprazole 30mg once daily for 4 weeks Refractory GERD: 30mg twice daily Esomeprazole 20mg once daily for 4 weeks (additional 4 weeks may be considered if healing is not complete) Lansoprazole 15mg once daily for 8 weeks Heartburn: 15mg once daily for 14 days Omeprazole 20mg once daily for 4 weeks Refractory GERD: 20 mg twice daily Omeprazole-sodium 20mg once daily for 4 weeks bicarbonate Heartburn: 20mg once daily for 4 weeks Pantoprazole 20mg once daily for 8 weeks
Rabeprazole 20mg once daily for 4 weeks NSAID Associated Gastric Ulcer Esomeprazole Treatment: 20mg once daily for 4-8 weeks ± Prevention: 20mg-40mg once daily for 6 months Lansoprazole Treatment: 30mg once daily for 8 weeks Prevention: 15mg once daily for 12 weeks Omeprazole Treatment: 20mg once daily for 4-8 weeks ± Prevention: 20mg once daily for 6 months ± Pantoprazole Prevention: 20mg once daily ± Pathological Hypersecretory Condition (e.g. Zollinger-Ellison Syndrome) Esomeprazole 40mg twice daily Lansoprazole 60mg once daily (up to 90mg twice daily) Omeprazole 60mg once daily (up to 120mg three times daily) Pantoprazole 40mg twice daily (up to 240mg daily) Rabeprazole 60mg once daily (up to 60mg twice daily) Active and Maintenance Therapy of Gastroduodenal Ulcers Lansoprazole Duodenal ulcer: Treatment: 15mg once daily for 4 weeks Maintenance: 15mg once daily Gastric ulcer: Treatment: 30mg once daily for 8 weeks Omeprazole Duodenal ulcer: 20mg once daily for 4 weeks (additional 4 weeks may be considered) Gastric ulcer: 40mg once daily for 4-8 weeks Omeprazole-sodium Duodenal ulcer: 20mg once daily for 4 weeks (additional 4 weeks may be bicarbonate considered) Gastric ulcer: 40mg once daily for 4-8 weeks Pantoprazole Duodenal ulcer: 40-80mg once daily for 4-8 weeks Gastric ulcer: 40mg once daily for 4 weeks (may extend for additional 2-4 weeks) ± Rabeprazole Duodenal ulcer: 20mg once daily for 4 weeks Gastric ulcer: 20mg once daily for 6 weeks ± H. Pylori Eradication Esomeprazole 40mg once daily as part of triple therapy/load regimen 20-40mg twice daily as part of clarithromycin/ levofloxacin sequential regimen 20mg twice daily as part of bismuth quadruple/ concomitant/ sequential/ hybrid/ levofloxacin triple regimen Lansoprazole 30mg twice daily as part of triple therapy
Omeprazole Pantoprazole Rabeprazole ± Off labeled use (dual therapy not recommended due to increasing resistance rates- Micromedex) 30mg twice daily as part of bismuth quadruple/ concomitant/ hybrid/ sequential/ levofloxacin triple regimen 30-60mg twice daily as part of levofloxacin sequential/ clarithromycin triple regimen 60mg once daily as part of LOAD regimen 40mg once daily as part of dual therapy/ LOAD regimen 20mg twice daily as part of triple therapy/ bismuth quadruple/ concomitant/ sequential / hybrid/ levofloxacin triple regimen 20-40mg twice daily as part of clarithromycin triple/ levofloxacin sequential/ quadruple regimen 40mg twice daily as part of bismuth quadruple/ concomitant/ sequential/ hybrid/ levofloxacin triple regimen 40-80mg twice daily as part of clarithromycin triple/ levofloxacin sequential regimen 80mg once daily as part of LOAD regimen 20mg twice daily as part of sequential/ levofloxacin triple regimen/ bismuth quadruple/ concomitant/hybrid regimen 20-40mg twice daily as part of clarithromycin triple regimen. Levofloxacin sequential regimen 40mg once daily as part of LOAD regimen References: 1. Katz, PO, Gerson, LB, et al. Am J Gastroenterol 2013; 108:308-328. 2. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017; 112(2):212-239.Shaheen NJ, Walk, GW, et al. Am J Gastroenteroladvance online publication, 3 November 2015; doi: 10.1038/ajg.2015:322. 3. Micromedex. Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Accessed September 21, 2016. 4. Prevacid [Prescribing Information] Deerfield, IL: Takeda Pharmaceuticals; December 2015. 5. Prilosec [Prescribing Information] Wilmington, DE: AstraZeneca; July 2016. 6. Aciphex/Aciphex Sprinkle [Prescribing Information] Woodcliff Lake, NJ: Eisai, Inc; April 2016. 7. Dexilant [Prescribing Information] Deerfield, IL: Takeda Pharmaceuticals; August 2016. 8. Nexium [Prescribing Information] Wilmington, DE: AstraZeneca; July 2016.
9. Zegerid [Prescribing Information] San Diego, CA: Santarus; June 2016. Change Control Date Change 11/15/2017 Document format updated New 2017 American College of Gastroenterology H. pylori guideline Expanded more on H. pylori regimens in the drug comparison table Added esomeprazole to formulary with quantity limit