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Drug Safety

, Volume 31, Issue 7, pp 627–636 | Cite as

Occurrence of Community-Acquired Respiratory Tract Infection in Patients Receiving Esomeprazole

Retrospective Analysis of Adverse Events in 31 Clinical Trials
  • Lennart Estborn
  • Svante JoelsonEmail author
Original Research Article

Abstract

Background: A potential causal association between an increase in gastric pH and a risk of community-acquired respiratory tract infection (RTI), specifically pneumonia, has been debated in relation to the use of potent gastric acid-suppressive medication.

Objective: To investigate the occurrence of community-acquired RTI, including pneumonia, in patients receiving esomeprazole versus placebo and other acid-suppressive agents in randomized clinical trials.

Methods: The AstraZeneca ARIADNE safety database was searched for comparative, controlled phase II–IV randomized, blinded clinical studies with esomeprazole and standard reporting of all adverse events (AEs). Pooled AE data were presented according to treatment comparison (esomeprazole versus placebo, esomeprazole 40 mg versus 20 mg daily, esomeprazole versus omeprazole, lansoprazole and/or ranitidine, respectively). Frequency and relative risk (RR), with 99% confidence interval (CI) and adjustment for time on treatment, were calculated for the following four AE categories: all RTIs; signs and symptoms potentially indicating RTI; lower RTI; and pneumonia.

Results: Thirty-one studies were identified, in which 16 583 patients received esomeprazole and 12 044 patients received either placebo or comparator acid-suppressive drugs. The occurrence of all four categories of AEs was similar between esomeprazole and placebo (all RTIs: 9.2% versus 8.5%; signs and symptoms of RTI: 1.8% versus 1.8%; lower RTI: 1.6% versus 1.5%; and pneumonia: 0.2% in both groups). The RR estimates were as follows: all RTIs, 0.93 (99% CI 0.78, 1.11); signs and symptoms of RTI, 0.85 (99% CI 0.57, 1.27); lower RTI, 0.92 (99% CI 0.59, 1.42); and pneumonia, 0.94 (99% CI 0.29, 3.07). The distribution of RTIs by patient sex and age showed a similar pattern in esomeprazole and placebo-treated patients. The comparisons of esomeprazole with the other comparator acid-suppressive drugs showed a similar pattern with only minor numerical differences in the occurrence of RTI between the drugs. There were no significant between-group differences with esomeprazole versus placebo for all four categories of AEs according to esomeprazole dosage, treatment indication and duration of treatment.

Conclusions: This pooled analysis found no causal association between acid-suppressive therapy with esomeprazole and increased risk of community-acquired RTI, including pneumonia, in patients receiving this agent for gastric acid-related disorders.

Keywords

Respiratory Tract Infection Omeprazole Ranitidine Lansoprazole Esomeprazole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors are employees of AstraZeneca (the manufacturer of esomeprazole), who provided financial support for this study. The authors own a limited number of shares in AstraZeneca. We thank Vicki Oldfield and Steve Winter, from Wolters Kluwer Health, who provided medical writing support, funded by AstraZeneca.

References

  1. 1.
    Laheij RJ, Van Ijzendoorn MC, Janssen MJ, et al. Gastric acid-suppressive therapy and community-acquired respiratory infections. Aliment Pharmacol Ther 2003; 18: 847–51PubMedCrossRefGoogle Scholar
  2. 2.
    Rousseau MC, Catala A, Blaya J. Association between pulmonary and digestive infections in patients receiving gastric acid-lowering medications for a long duration. Brain Inj 2003; 17: 883–7PubMedCrossRefGoogle Scholar
  3. 3.
    Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004; 292: 1955–60PubMedCrossRefGoogle Scholar
  4. 4.
    Canani RB, Cirillo P, Roggero P, et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics 2006; 117: 817–20CrossRefGoogle Scholar
  5. 5.
    Gulmez SE, Holm A, Frederiksen H, et al. Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch Intern Med 2007; 167: 950–5PubMedCrossRefGoogle Scholar
  6. 6.
    Gregor JC. Acid suppression and pneumonia: a clinical indication for rational prescribing. JAMA 2004; 292: 2012–3PubMedCrossRefGoogle Scholar
  7. 7.
    Detsky ME, Juurlink DN. Does gastric acid suppression increase the risk of community-acquired pneumonia? CMAJ 2005; 172: 331PubMedCrossRefGoogle Scholar
  8. 8.
    Sataloff RT. Community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2005; 293: 795–6PubMedCrossRefGoogle Scholar
  9. 9.
    Talley NJ, Venables TL, Green JR, et al. Esomeprazole 40mg and 20mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months. Eur J Gastroenterol Hepatol 2002; 14: 857–63PubMedCrossRefGoogle Scholar
  10. 10.
    Data on file, AstraZeneca, 1999Google Scholar
  11. 11.
    Vakil NB, Shaker R, Johnson DA, et al. The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomised, double-blind, placebo-controlled study of efficacy and safety. Aliment Pharmacol Ther 2001; 15(7): 927–35PubMedCrossRefGoogle Scholar
  12. 12.
    Johnson DA, Benjamin SB, Vakil NB, et al. Esomeprazole once daily for 6 months is effective therapy for maintenance of healing of erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomised, double-blind, placebo-controlled study of efficacy and safety. Am J Gasteroenterol 2001; 96: 27–34CrossRefGoogle Scholar
  13. 13.
    Talley NJ, Lauritsen K, Tunturi-Hihnala H, et al. Esomeprazole 20mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of ‘on-demand’ therapy for 6 months. Aliment Pharmacol Ther 2001; 15: 347–54PubMedCrossRefGoogle Scholar
  14. 14.
    Katz PO, Castell DO, Levine D. Esomeprazole resolves chronic heartburn in patients without erosive oesophagitis. Aliment Pharmacol Ther 2003; 18: 875–82PubMedCrossRefGoogle Scholar
  15. 15.
    Johnsson F, Hatlebakk JG, Klintenberg AC, et al. One-week esomeprazole treatment: an effective confirmatory test in patients with suspected gastroesophageal reflux disease. Scand J Gastroenterol 2003; 38: 354–9PubMedCrossRefGoogle Scholar
  16. 16.
    Armstrong D, Talley NJ, Lauritsen K. The role of acid suppression in patients with endoscopy-negative reflux disease: the effect of treatment with esomeprazole or omeprazole. Aliment Pharmacol Ther 2004; 20: 413–21PubMedCrossRefGoogle Scholar
  17. 17.
    Kahrilas PJ, Falk GW, Johnson DA, et al. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomised controlled trial. Aliment Pharmacol Ther 2000; 14: 1249–58PubMedCrossRefGoogle Scholar
  18. 18.
    Schmitt C, Lightdale CJ, Hwang C, et al. A multicenter, randomised, double-blind, 8-week comparative trial of standard doses of esomeprazole (40 mg) and omeprazole (20 mg) for the treatment of erosive esophagitis. Dig Dis Sci 2006; 51: 844–50PubMedCrossRefGoogle Scholar
  19. 19.
    Lightdale CJ, Schmitt C, Hwang C, et al. A multicenter, randomised, double-blind, 8-week comparative trial of low-dose esomeprazole (20 mg) and standard-dose omeprazole (20 mg) in patients with erosive esophagitis. Dig Dis Sci 2006; 51: 852–7PubMedCrossRefGoogle Scholar
  20. 20.
    Richter JE, Kahrilas PJ, Johanson J, et al. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomised controlled trial. Am J Gastroenterol 2001; 96: 656–65PubMedCrossRefGoogle Scholar
  21. 21.
    Fennerty MB, Johanson JF, Hwang C, et al. Efficacy of esomeprazole 40mg vs. lansoprazole 30mg for healing moderate to severe erosive oesophagitis. Aliment Pharmacol Ther 2005; 21: 455–63PubMedCrossRefGoogle Scholar
  22. 22.
    DeVault KR, Johanson JF, Johnson DA, et al. Maintenance of healed erosive esophagitis: a randomised six-month comparison of esomeprazole twenty milligrams with lansoprazole fifteen milligrams. Clin Gastroenterol Hepatol 2006; 4: 852–9PubMedCrossRefGoogle Scholar
  23. 23.
    Lauritsen K, Devière J, Bigard MA, et al. Esomeprazole 20mg and lansoprazole 15mg in maintaining healed reflux oesophagitis: Metropole study results. Aliment Pharmacol Ther 2003; 17: 333–41PubMedCrossRefGoogle Scholar
  24. 24.
    Castell DO, Kahrilas PJ, Richter JE, et al. Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol 2002; 97: 575–83PubMedCrossRefGoogle Scholar
  25. 25.
    Armstrong D, Vieth M, Deprez P, et al. Esomeprazole therapy and esophageal histology in endoscopy-negative reflux disease (ENRD): the CHEER study [abstract]. Gastroenterology 2003; 124 (4 Suppl. 1): A416Google Scholar
  26. 26.
    Hawkey C, Talley NJ, Yeomans ND, et al. Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors. Am J Gastroenterol 2005; 100: 1028–36PubMedCrossRefGoogle Scholar
  27. 27.
    Hawkey CJ, Talley NJ, Scheiman JM, et al. Maintenance treatment with esomeprazole following initial relief of NSAID-associated upper GI symptoms: the NASA2 and SPACE2 studies. Arth Res Ther 2007; 9: R17CrossRefGoogle Scholar
  28. 28.
    Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using nonselective NSAIDs and COX-2 inhibitors. Am J Gastroenterol 2006; 101: 701–10PubMedCrossRefGoogle Scholar
  29. 29.
    Goldstein JL, Johanson JF, Suchower LJ, et al. Healing of gastric ulcers with esomeprazole versus ranitidine in patients who continued to receive NSAID therapy: a randomized trial. Am J Gastroenterol 2005; 100: 2650–7PubMedCrossRefGoogle Scholar
  30. 30.
    Goldstein JL, Johanson JF, Hawkey CJ, et al. Clinical trial: healing of NSAID-associated gastric ulcers in patients continuing NSAID therapy: a randomised study comparing ranitidine with esomeprazole. Aliment Pharmacol Ther 2007; 26: 1101–11PubMedCrossRefGoogle Scholar
  31. 31.
    Talley NJ, Vakil N, Lauritsen K, et al. Randomized-controlled trial of esomeprazole in functional dyspepsia patients with epigastric pain or burning: does a 1-week trial of acid suppression predict symptom response? Aliment Pharmacol Ther 2007; 26: 673–82PubMedCrossRefGoogle Scholar
  32. 32.
    Veldhuyzen van Zanten S, Flook N, Talley NJ, et al. One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks’ treatment with esomeprazole: a randomised, placebo-controlled study. Aliment Pharmacol Ther 2007; 26: 665–72CrossRefGoogle Scholar
  33. 33.
    Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40mg twice daily on asthma: a randomised placebo-controlled trial. Am J Respir Crit Care Med 2006; 173: 1091–7PubMedCrossRefGoogle Scholar
  34. 34.
    Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol 1993; 137: 977–88PubMedGoogle Scholar
  35. 35.
    British Thoracic Society Standards of Care Committee. BTS Guidelines for the management of community acquired pneumonia in adults. Thorax 2001; 56 Suppl. 4: IV1–64CrossRefGoogle Scholar
  36. 36.
    Rothman KJ. A potential bias in safety evaluation during open-label extensions of randomized clinical trials. Pharmacoepidemiol Drug Saf 2004; 13: 295–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Safety Surveillance CVGI, Clinical Drug SafetyAstraZeneca R&DMölndalSweden

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