Criteria for Outpatient Use Guidelines
Disclaimer
The information contained at this site and available for download is for the convenience of the public. Some documents are made available in specific file formats to respond to specific requests.
The Texas Health and Human Services Commission is not responsible for any errors in transmission or any errors or omissions in the documents.
Proton Pump Inhibitors
[Developed, October 2000 (formerly a component of Anti-Ulcer Therapy criteria); Revised, December 2001; October 2002, November 2003; December 2005; June 2009; September 2009]
Information on indications for use or diagnosis is assumed to be unavailable. All criteria may be applied retrospectively; prospective application is indicated with [*].
1.* Dosage
Proton pump inhibitors (PPIs) are FDA-approved for use in duodenal and gastric ulcers, esophagitis, gastroesophageal reflux disease (GERD), hypersecretory conditions, and as part of combination therapy for Helicobacter pylori eradication.
Adults
Maximum daily adult doses for PPIs when prescribed as acute and maintenance therapy are summarized in Tables 1 and 2. Dosages exceeding these recommended values will be reviewed.
| DRUG | MAXIMUM DOSE |
|---|---|
| dexlansoprazole (Kapidex®) | erosive esophagitis: 60 mg/day GERD: 30 mg/day |
| esomeprazole (Nexium®) | erosive esophagitis: 40 mg/day GERD: 20 mg/day H. pylori eradication: 40 mg/day |
| lansoprazole (Prevacid®) | duodenal ulcer: 15 mg/day erosive esophagitis: 30 mg/day gastric ulcer: 30 mg/day gastric ulcer associated with NSAIDs: 30 mg/day GERD: 15 mg/day H. pylori eradication: triple therapy – 60 mg/day dual therapy – 90 mg/day hypersecretory conditions: 180 mg/day |
| omeprazole (Prilosec®, Zegerid®, generics) | duodenal ulcer: 20 mg/day erosive esophagitis: 20 mg/day gastric ulcer: 40 mg/day GERD: 20 mg/day H. pylori eradication: triple therapy – 40 mg/day in divided doses dual therapy – 40 mg/day hypersecretory conditions: 360 mg/day upper GI bleeding risk reduction (Zegerid® only): 40 mg/day |
| pantoprazole (Protonix®) | erosive esophagitis: 40 mg/day hypersecretory conditions: 240 mg/day |
| rabeprazole (Aciphex®) | duodenal ulcer: 20 mg/day erosive esophagitis: 20 mg/day GERD: 20 mg/day H. pylori eradication: 40 mg/day hypersecretory conditions: 120 mg/day |
| DRUG | MAXIMUM DOSE |
|---|---|
| dexlansoprazole | erosive esophagitis: 30 mg/day |
| esomeprazole | erosive esophagitis: 20 mg/day risk reduction of NSAID-associated gastric ulcer: 40 mg/day |
| lansoprazole | duodenal ulcer: 15 mg/day gastric ulcers associated with NSAIDs: 15 mg/day erosive esophagitis: 15 mg/day hypersecretory conditions: 180 mg/day |
| omeprazole | erosive esophagitis: 20 mg/day hypersecretory conditions: 360 mg/day |
| pantoprazole | erosive esophagitis: 40 mg/day hypersecretory conditions: 240 mg/day |
| rabeprazole | hypersecretory conditions: 120 mg/day erosive esophagitis: 20 mg/day GERD: 20 mg/day |
Pediatrics
Safety and efficacy of dexlansoprazole and pantoprazole in patients less than 18 years of age have not been established.
Esomeprazole, lansoprazole, omeprazole, and rabeprazole are FDA-approved for use in pediatric patients; doses are age-dependent. The maximum recommended daily pediatric doses for these PPIs are summarized in Table 3. Dosages exceeding these recommendations will be reviewed.
| DRUG | MAXIMUM DOSE |
|---|---|
| esomeprazole | acute therapy: 1 to 11 years of age: erosive esophagitis: > 20 kg - 20 mg/day < 20 kg – 10 mg/day GERD: 10 mg/day 12 to 17 years of age: GERD: 40 mg/day |
| lansoprazole | acute therapy: 1 to 11 years of age: erosive esophagitis: 60 mg/day GERD: 60 mg/day > 12 years of age: GERD: 15 mg/day maintenance dose: 12 years and older: erosive esophagitis: 15 mg/day |
| omeprazole | acute therapy: > 1 year of age: esophagitis, GERD: 5 to 10 kg – 5 mg /day 10 to 20 kg – 10 mg/day > 20 kg - 20 mg/day |
| rabeprazole | acute therapy: > 12 years of age: GERD: 20 mg/day |
Although not FDA-approved due to limited availability of guidelines and well-designed clinical trials, select proton pump inhibitors have been utilized in combination with antibiotic therapy to manage H. pylori in pediatric patients. Drug regimens have included omeprazole 1 mg/kg/day or lansoprazole 0.45 to 0.75 mg/kg/day in combination with amoxicillin and clarithromycin for 7 to 10 days. The 2000 North American Society for Pediatric Gastroenterology and Nutrition H. pylori treatment recommendations (currently under revision) are summarized in Table 4.
| TREATMENT OPTION | ORAL DOSAGE |
|---|---|
Option 1: |
50 mg/kg/day up to 1 g twice daily |
Option 2: |
50 mg/kg/day up to 1 g twice daily |
Option 3: |
15 mg/kg/day up to 500 mg twice daily |
Option 4*: |
262 mg four times daily 50 mg/kg/day up to 1 g twice daily 50 mg/kg/day up to 1 g twice daily 15 mg/kg/day up to 500 mg twice daily |
*second-line option
^only utilized in children 12 years of age and older
2. Duration of Therapy
Clinical studies document a maximum treatment duration of 56 days (eight weeks) for anti-ulcer therapy in the treatment of acute duodenal ulcer and gastric ulcer. The Texas Vendor Drug Program limits reimbursement for PPIs and related drugs to 62 days per calendar year at the maximum daily acute dose listed for duodenal ulcer and gastric ulcer in Table 1. This treatment duration has been allotted to allow a 31 day supply per prescription. The prescribing health care provider may continue acute dosage regimens for periods longer than 62 days per calendar year for patients with conditions such as hypersecretory disease states, esophagitis, or GERD. A diagnosis must be written on the prescription for acute treatment regimens exceeding the recommended treatment duration of 62 days per calendar year. Treatment regimens at acute dosage levels lasting longer than four months (16 weeks) will be reviewed.
Esomeprazole, when prescribed for risk reduction of NSAID-associated gastric ulcer, may be administered for up to six months, as controlled studies for this indication do not extend beyond this time period. Similarly, lansoprazole may be administered for up to 8 weeks when prescribed for healing of NSAID- induced gastric ulcers and up to 12 weeks for risk reduction of NSAID-associated gastric ulcers, as controlled studies have not evaluated longer treatment durations. Treatment regimens for NSAID- associated gastric ulcers extending beyond six months for esomeprazole, 8 weeks for lansoprazole 30 mg, and 12 weeks for lansoprazole 15 mg will be reviewed.
Unless otherwise specified, maintenance therapy, at the recommended daily maintenance dose (Table 2 and Table 3), may be continued indefinitely based on patient need. PPI treatment duration in adults for H. pylori eradication is summarized in Table 5.
| DRUG | RECOMMENDED THERAPY DURATION |
|---|---|
| esomeprazole | with triple therapy: 10 days |
| lansoprazole | with dual therapy: 14 days with triple therapy: 14 days |
| omeprazole | with ulcer present at treatment initiation, dual or triple therapy: 28 days without ulcer present at treatment initiation, dual therapy: 14 days triple therapy: 10 days |
| rabeprazole | with triple therapy: 7 days |
Pediatric treatment durations for H. pylori eradication regimens reported in guidelines and clinical trials range from 7 to 14 days.
3.* Duplicative Therapy
The combination of two or more proton pump inhibitors is not supported by the current literature. Additional clinical benefit is not realized when multiple proton pump inhibitors are prescribed adjunctively. Therefore, concurrent use of multiple proton pump inhibitors will be reviewed.
4.* Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions.
The following drug-drug interactions are considered clinically relevant for proton pump inhibitors. Only those drug-drug interactions identified as clinical significance level 1 or contraindicated, or those considered life-threatening which have not yet been classified will be reviewed:
a. Clopidogrel (Plavix®) [clinical significance level – major (DrugReax); 1 (DIF)]
Recent data suggest that concurrent administration of PPIs with clopidogrel may attenuate clopidogrel effects on platelet aggregation and increase the potential risk of secondary acute cardiovascular events following percutaneous coronary intervention or acute coronary syndrome. While the exact mechanism for this interaction is unknown, PPIs may delay or minimize clopidogrel conversion to its active form by competitively inhibiting CYP2C19. Histamine H2- receptor antagonists or pantoprazole may be suitable alternatives for patients prescribed clopidogrel requiring acid suppressive therapy, as these agents have not been associated with increased cardiovascular events when administered adjunctively with clopidogrel.
b. Select Azole Antifungal Agents [(itraconazole (Sporanox®), ketoconazole (Nizoral®), posaconazole (Noxafil®)] [clinical significance level – moderate (DrugReax); 2 (DIF); 3 (Hansten & Horn)]
The azole antifungals, itraconazole, ketoconazole, and posaconazole, are dependent on an acidic environment for favorable absorption. PPIs increase gastric pH and subsequently decrease absorption and antifungal effectiveness of these select azole antifungals. Combined use of PPIs and itraconazole, ketoconazole, or posaconazole should be avoided, if possible. If the PPI-select azole antifungal combination is necessary, administering the azole antifungal with an acidic beverage (e.g., Coke) may enhance absorption and improve therapeutic effectiveness. Observe patients routinely for reduced antifungal effect when PPIs are administered concurrently with these select azole antifungals.
c. Protease Inhibitors [e.g., atazanavir (Reyataz®), indinavir (Crixivan®), nelfinavir (Viracept®), saquinavir (Invirase®)] [clinical significance level – major (DrugReax); 1 (DIF); atazanavir – 2, other protease inhibitors - 3 (Hansten & Horn)]
Concurrent administration of PPIs and atazanavir, indinavir, and nelfinavir may result in reduced protease inhibitor serum levels and decreased efficacy, while combined administration of PPIs with saquinavir may result in enhanced saquinavir absorption and increased serum concentrations. PPIs interfere with the solubility of protease inhibitors as atazanavir, indinavir, and nelfinavir solubility decreases with increasing pH and saquinavir absorption is enhanced with increasing gastric pH. Combined administration of PPIs and atazanavir or nelfinavir is not recommended by the manufacturer as plasma atazanavir and nelfinavir concentrations are significantly decreased with this drug combination. Patients prescribed PPIs concurrently with indinavir should be monitored for reductions in antiviral efficacy. Patients prescribed PPIs concurrently with saquinavir should be observed for enhanced pharmacologic and/or adverse effects. Concomitant administration of atazanavir or nelfinavir with PPIs is not recommended and will be reviewed.
d. Dasatinib (Sprycel®) [clinical significance level – major (DrugReax); 2 (DIF)]
Dasatinib administered concomitantly with a PPI for an extended duration may result in reduced dasatinib exposure and serum concentrations as dasatinib is dependent on an acidic gastric pH for solubility and absorption. Adjunctive administration of dasatinib with PPIs is not recommended by the manufacturer. Antacids are an alternative for dasatinib-treated patients requiring acid suppressive therapy, and should be administered 2 hours before or 2 hours after the dasatinib dose for optimal efficacy.
e. Delavirdine (Rescriptor®) [clinical significance level – major (DrugReax); 3 (Hansten & Horn)]
Concurrent administration of PPIs with delavirdine for an extended treatment duration may result in reduced delavirdine absorption, decreased delavirdine serum concentrations, and attenuated delavirdine efficacy as delavirdine is dependent on an acidic gastric pH for absorption. Separating drug doses may not improve delavirdine absorption as PPIs affect gastric pH for a prolonged time period. Antacids may be an alternative for delavirdine-treated patients requiring acid suppressive therapy. Antacid and delavirdine doses should be separated by at least one hour, however, as clinical studies have shown impaired delavirdine absorption and reduced delavirdine serum concentrations when administered adjunctively with antacids. Concomitant administration of PPIs and delavirdine is not recommended.
f. Erlotinib (Tarceva®) [clinical significance level – major (DrugReax); 2 (DIF)]
Erlotinib administered concomitantly with a PPI for an extended duration may result in reduced erlotinib exposure and serum concentrations as erlotinib is dependent on an acidic gastric pH for solubility and absorption. Adjunctive administration of erlotinib with PPIs is not recommended by the manufacturer. Antacids are an alternative for erlotinib-treated patients requiring acid suppressive therapy, and should be administered 2 hours before or 2 hours after the erlotinib dose for optimal efficacy.
References
- Drug Facts and Comparisons. Facts and Comparisons 4.0 [database online]. St. Louis, MO: Wolters Kluwer Health, Inc.; 2009. Available at: http://online.factsandcomparisons.com. Accessed June 10th, 2009.
- Klasko RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, CO, USA. Available at: http://www.thomsonhc.com . Accessed June 10th, 2009.
- AHFS Drug Information 2009 [book online]. Jackson, WY: Teton Data Systems, Version 6.1.0, 2009. Based on: McEvoy GK, editor. AHFS drug information 2009. Bethesda (MD): American Society of Health-System Pharmacists; 2009. Stat!Ref Electronic Medical Library.
- Hansten PD, Horn JR, eds. Drug interactions analysis and management. St. Louis, MO: Wolters Kluwer Health, Inc.; 2009.
- Tatro DS, ed. Drug interaction facts. St. Louis: Wolters Kluwer Health, Inc.; 2009.
- Posaconazole (Noxafil®) Package Insert. Schering-Plough, February 2009.
- Dasatinib (Sprycel®) Package Insert. Bristol-Myers Squibb, May 2009.
- Delavirdine (Rescriptor®) Package Insert. Pfizer, Inc., May 2008.
- Erlotinib (Tarceva®) Package Insert. OSI Pharmaceuticals, Inc., April 2009.
- Atazanavir (Reyataz®) Package Insert. Bristol-Myers Squibb, April 2009.
- Nelfinavir (Viracept®) Package Insert. Agouron Pharmaceuticals, Inc., September 2008.
- Walan A, Bader JP, Classen M, Lamers CBHW, Piper DW, Rutgersson K, Eriksson S. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med. 1989;320:69-75.
- Van Der Meer JWM, Keuning JJ. The influence of gastric acidity on the bioavailability of ketoconazole. J Antimicrob Chemother. 1980;6:552-4.
- Peghini PL, Katz PO, Castell DO. Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: A controlled study in normal subjects.Gastroenterology. 1998;115:1335-9.
- Cross LB, Justice LN. Combination drug therapy for gastroesophageal reflux disease. Ann Pharmacother. 2002;36:912-6.
- Graham DY, Agrawal NM, Campbell DR, et al. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole. Arch Intern Med. 2002;162:169-75.
- Kahrilas PJ. Gastroesophageal reflux disease. N Engl J Med. 2008;359(16):1700-7.
- DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal
reflux disease. Am J Gastroenterol. 2005;100:190-200. - CheyWD, Wong BCY, and the Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808-25.
- Lazzaroni M, Porro GB. Management of NSAID-induced gastrointestinal toxicity: focus on proton pump inhibitors. Drugs. 2009;69(1):51-69.
- Shi S, Klotz U. Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol. 2008;64(10):935-51.
- Gold BD, Colletti RB, Abbott M, et al. Medical position statement: The North American Society for Pediatric Gastroenterology and Nutrition. Helicobacter pylori infection in children: recommendations for diagnosis and treatment. J Pediatr Gastroenterol Nutr. 2000;31:490-7.
- Shashidhar H, Peters J, Lin CH, et al. A prospective trial of lansoprazole triple therapy for pediatric Helicobacter pylori infection. J Pediatr Gastroenterol Nutr. 2000;30:276-82.
- Behrens R, Lang T, Keller KM, et al. Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial. Arch Dis Child. 1999;81:68-70.
- Zimmermann AE, Walters JK, Katona BG, et al. A review of omeprazole use in the treatment of acid-related disorders in children. Clin Ther. 2001;23:660-79.
- Marchetti F, Gerarduzzi T, Ventura A. Proton pump inhibitors in children: a review. Dig Liver Dis. 2003;35:738-46.
Prepared by: Drug Information Service, The University of Texas Health Science Center at San Antonio, and the College of Pharmacy, The University of Texas at Austin.