Clinical Drug Investigation

, Volume 33, Issue 9, pp 689–697 | Cite as

Fixed-Dose Ibuprofen/Famotidine: A Review of Its Use to Reduce the Risk of Gastric and Duodenal Ulcers in Patients Requiring NSAID Therapy

  • Emma D. Deeks
Adis Drug Evaluation


A fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and the histamine H2 receptor antagonist famotidine (ibuprofen/famotidine; DUEXIS®) is now available for the symptomatic treatment of arthritic symptoms and to reduce the risk of upper gastrointestinal (GI) ulcers in patients who require ibuprofen therapy. The gastroprotective efficacy of oral ibuprofen/famotidine 800/26.6 mg three times daily in patients requiring NSAID therapy for inflammatory conditions and/or pain was evaluated in two 24-week, well-designed trials (REDUCE-1 and -2). According to the post-adjudication analysis of these studies, ibuprofen/famotidine significantly reduced the life table estimated rate of gastric ulcers (primary endpoint of REDUCE-1) but not upper GI ulcers (i.e. gastric or duodenal ulcers) [primary endpoint of REDUCE-2] compared with ibuprofen alone. When life table estimated rates of secondary endpoints were assessed, significantly fewer recipients of the fixed-dose combination than of ibuprofen alone developed upper GI ulcers or duodenal ulcers in REDUCE-1, whereas the between-group difference in gastric ulcers and duodenal ulcers was considered to be nonsignificant in REDUCE-2 because of hierarchical testing. However, in a prespecified pooled analysis of REDUCE-1 and -2, the rate of upper GI ulcers as well as each of the upper GI ulcer components was significantly lower with ibuprofen/famotidine than with ibuprofen. Ibuprofen/famotidine was generally well tolerated, with a tolerability profile consistent with those established for the individual agents.


Ibuprofen Clopidogrel Duodenal Ulcer Gastric Ulcer Misoprostol 
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.



The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

Conflict of interest

This document has been written by in-house editorial staff of Adis Publications, who have no conflict of interest.


  1. 1.
    Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728–38.PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385–91.PubMedCrossRefGoogle Scholar
  3. 3.
    Roth SH. Coming to terms with nonsteroidal anti-inflammatory drug gastropathy. Drugs. 2012;72(7):873–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Musumba C, Pritchard DM, Pirmohamed M. Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers. Aliment Pharmacol Ther. 2009;30(6):517–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Bello AE. DUEXIS® (ibuprofen 800 mg, famotidine 26.6 mg): a new approach to gastroprotection for patients with chronic pain and inflammation who require treatment with a nonsteroidal anti-inflammatory drug. Ther Adv Musculoskel Dis. 2012;4(5):327–39.Google Scholar
  6. 6.
    Horizon Pharma USA Inc. DUEXIS (ibuprofen and famotidine) tablets, for oral use: US prescribing information. 2011. Accessed 1 Jul 2013.
  7. 7.
    Bennett A. Horizon scanning: Duexis (ibuprofen/famotidine) receives marketing authorisation for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis [media release]. 8 Mar 2013.
  8. 8.
    Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009;17(6):275–342.PubMedCrossRefGoogle Scholar
  9. 9.
    Langtry HD, Grant SM, Goa KL. Famotidine: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in peptic ulcer disease and other allied diseases. Drugs. 1989;38(4):551–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Simon TJ, Berger ML, Hoover ME, et al. A dose ranging study of famotidine in prevention of gastroduodenal lesions associated with non-steroidal anti-inflammatory drugs (NSAIDS): results of a U.S. multicentre trial [abstract no. 116]. Am J Gastroenterol. 1994;89(9):1644.Google Scholar
  11. 11.
    Tidmarsh G, Rodriguez SB. Famotidine (FAM) administered orally three times daily (tid) produces better gastric acid suppression and control than does twice daily (bid) administration of the same total daily dose [abstract no. T1971]. Gastroenterology. 2009;136(5 Suppl 1):A611–2.Google Scholar
  12. 12.
    Hudson N, Taha AS, Russell RI, et al. Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration. Gastroenterology. 1997;112(6):1817–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Taha AS, Hudson N, Hawkey CJ, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. N Engl J Med. 1996;334(22):1435–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107(3):389–96.PubMedCrossRefGoogle Scholar
  15. 15.
    Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gastroenterology. 2010;138(1):82–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Miyake K, Ueki N, Suzuki K, et al. Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in Japanese patients with rheumatoid arthritis: the current situation and a prospective controlled-study of the preventive effects of lansoprazole or famotidine. Aliment Pharmacol Ther. 2005;21(Suppl 2):67–72.PubMedCrossRefGoogle Scholar
  17. 17.
    US FDA Center for Drug Evaluation and Research. Application number 022519Orig1s000: clinical pharmacology and biopharmaceutics review(s). 2011. Accessed 1 Jul 2013.
  18. 18.
    US FDA Center for Drug Evaluation and Research. Application number 022519Orig1s000: pharmacology review(s). 2010. Accessed 1 Jul 2013.
  19. 19.
    Tidmarsh G, Rodriguez SB. HZT-501, a novel combination of ibuprofen (Ibu) and famotidine (FAM), provides pharmacokinetics comparable to that of commercially available Ibu and FAM in a patient-friendly dosing form: evaluation in healthy and renally-impaired subjects [abstract no. T1974]. Gastroenterology. 2009;136(5 Suppl):A612.Google Scholar
  20. 20.
    Grahn A, Jung D, Kramer W, et al. HZT-501, a novel combination tablet of ibuprofen and famotidine, provides pharmacokinetics comparable to European commercially available ibuprofen in a patient-friendly dosing form: evaluation in healthy subjects [abstract no. 82]. Am J Gastroenterol. 2010;105(S1):S31.Google Scholar
  21. 21.
    Katoh Y. Impact of the influence of H2 receptor antagonist (famotidine) on the antiplatelet therapy (aspirin and clopidogrel) [abstract no. AS-212]. Am J Cardiol. 2011;107(8 Suppl):79A.Google Scholar
  22. 22.
    Wang X, Boffito M, Zhang J, et al. Effects of the H2-receptor antagonist famotidine on the pharmacokinetics of atazanavir–ritonavir with or without tenofovir in HIV-infected patients. AIDS Patient Care STDS. 2011;25(9):509–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Bourre-Tessier J, Haraoui B. Methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. J Rheumatol. 2010;37(7):1416–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Laine L, Kivitz AJ, Bello AE, et al. Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers [published erratum appears in Am J Gastroenterol 2012;107(8):1272]. Am J Gastroenterol. 2012;107(3):379–86.PubMedCrossRefGoogle Scholar
  25. 25.
    Schiff M, Weinblatt M, Genovese M, et al. Independent predictors for the development of upper gastrointestinal ulcers with a NSAID: results from two large trials of a single-tablet combination of ibuprofen-famotidine vs. ibuprofen alone [abstract no. THU0383]. European League Against Rheumatism 11th Annual Congress, 16–19 Jun 2010, Rome.Google Scholar
  26. 26.
    Weinblatt ME, Genovese MC, Kivitz AJ, et al. Efficacy, safety and tolerability of HZT-501, including users of low-dose aspirin, a single-tablet combination of ibuprofen-famotidine: results of two phase 3 trials [abstract no. 945]. Arthritis Rheum. 2010;62(10 Suppl):S391–2.Google Scholar
  27. 27.
    Schiff MH, Genovese MC, Bello AE, et al. Efficacy, safety, and tolerability of a single-tablet combination of ibuprofen-famotidine: results in patients who require nonsteroidal anti-inflammatory drugs for osteoarthritis, rheumatoid arthritis, or chronic pain [abstract no. 264 plus poster]. American Academy of Pain Medicine annual meeting, 23–26 Feb 2012, Palm Springs.Google Scholar
  28. 28.
    Horizon Pharma Inc. Efficacy and safety study of HZT-501 in subjects requiring nonsteroidal anti-inflammatory drug (NSAID) treatment [ identifier NCT00450216]. US National Institutes of Health, [online]. 2013. Accessed 1 Jul 2013.
  29. 29.
    Horizon Pharma Inc. Efficacy and safety study of HZT-501 in reducing the risk of ibuprofen-associated ulcers [ identifier NCT00450658]. US National Institutes of Health, [online]. 2013. Accessed 1 Jul 2013.
  30. 30.
    Goldstein JL, Lakhanpal S, Cohen SB, et al. Long term safety of an NSAID with built-in gastroprotection for treatment of pain and inflammation related to oa and ra: comparative results from blinded and open label one year safety trials of a single-tablet combination of ibuprofen-famotidine [abstract no. Mo1215]. Gastroenterology. 2011;140(5 Suppl 1):S585.Google Scholar
  31. 31.
    Goldstein J, Lakhanpal S, Cohen S, et al. Decreased NSAID associated treatment emergent dyspepsia and increased patient satisfaction associated with ibuprofen/famotidine combination tablet: SODA results from a 12-month trial [abstract no. 124]. Am J Gastroenterol. 2012;107(Suppl 1):S52–3.Google Scholar
  32. 32.
    Rabeneck L, Wristers K, Goldstein JL, et al. Reliability, validity, and responsiveness of severity of dyspepsia assessment (SODA) in a randomized clinical trial of a COX-2-specific inhibitor and traditional NSAID therapy. Am J Gastroenterol. 2002;97(1):32–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Chan FK, Abraham NS, Scheiman JM, et al. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents. Am J Gastroenterol. 2008;103(11):2908–18.PubMedCrossRefGoogle Scholar
  34. 34.
    Rostom A, Moayyedi P, Hunt R. Canadian consensus guidelines on long-term nonsteroidal anti-inflammatory drug therapy and the need for gastroprotection: benefits versus risks. Aliment Pharmacol Ther. 2009;29(5):481–96.PubMedCrossRefGoogle Scholar
  35. 35.
    US FDA. Drug safety communications. 2011 and 2012. Accessed 1 Jul 2013.
  36. 36.
    Sugano K. Single-tablet double-dose famotidine plus ibuprofen decreases endoscopic upper GI ulcers compared with ibuprofen alone. Evid Based Med. 2012;18(1):26–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Chan FKL. Single-tablet ibuprofen/double-dose famotidine for reduction of gastric and duodenal ulcers (REDUCE trials): what can be reduced? Am J Gastroenterol. 2012;107(3):387–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Graham DY. Endoscopic ulcers are neither meaningful nor validated as a surrogate for clinically significant upper gastrointestinal harm. Clin Gastroenterol Hepatol. 2009;7(11):1147–50.PubMedCrossRefGoogle Scholar
  39. 39.
    Kuan R, Holt RJ, Johnson KE, et al. Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis. Clin Ther. 2013;35(3):321–32.PubMedCrossRefGoogle Scholar
  40. 40.
    US FDA Center for Drug Evaluation and Research. Application number 022519Orig1s000: medical review(s). 2011. Accessed 1 Jul 2013.

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

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