Clinical Drug Investigation

, Volume 32, Issue 4, pp 221–233 | Cite as

Non-Steroidal Anti-Inflammatory Drugs and Gastroprotection with Proton Pump Inhibitors

A Focus on Ketoprofen/Omeprazole
Review Article

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules.

The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen.

Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature.

The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components.

Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation ensures compliance with the gastroprotective prophylaxis, as whenever the NSAID is taken, the PPI is co-administered. Additionally, the once-daily formulation has the potential to improve adherence to anti-inflammatory therapy.

References

  1. 1.
    Singh G. Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System. Am J Ther 2000 Mar; 7(2): 115–21PubMedCrossRefGoogle Scholar
  2. 2.
    Naesdal J, Brown K. NSAID-associated adverse effects and acid control aids to prevent them: a review of current treatment options. Drug Saf 2006; 29(2): 119–32PubMedCrossRefGoogle Scholar
  3. 3.
    Becker JC, Domschke W, Pohle T. Current approaches to prevent NSAID-induced gastropathy: COX selectivity and beyond. Br J Clin Pharmacol 2004 Dec; 58(6): 587–600PubMedCrossRefGoogle Scholar
  4. 4.
    Singh G, Rosen Ramey D. NSAID induced gastrointestinal complications: the ARAMIS perspective —1997. Arthritis, Rheumatism, and Aging Medical Information System. J Rheumatol Suppl. 1998 May; 51: 8–16PubMedGoogle Scholar
  5. 5.
    Straus WL, Ofman JJ, MacLean C, et al. Do NSAIDs cause dyspepsia? A meta-analysis evaluating alternative dyspepsia definitions. Am J Gastroenterol 2002 Aug; 97(8): 1951–8PubMedCrossRefGoogle Scholar
  6. 6.
    Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am 1996 Jul; 6(3): 489–504PubMedGoogle Scholar
  7. 7.
    Vonkeman HE, Fernandes RW, van de Laar MA. Under-utilization of gastroprotective drugs in patients with NSAID-related ulcers. Int J Clin Pharmacol Ther 2007 May; 45(5): 281–8PubMedGoogle Scholar
  8. 8.
    Sturkenboom MC, Burke TA, Dieleman JP, et al. Under-utilization of preventive strategies in patients receiving NSAIDs. Rheumatology (Oxford) 2003 Nov; 42Suppl. 3: iii23–31Google Scholar
  9. 9.
    Clinard F, Bardou M, Sgro C, et al. Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in general practice: a general practitioner-based survey in France. Eur J Clin Pharmacol 2001 Dec; 57(10): 737–43PubMedCrossRefGoogle Scholar
  10. 10.
    Abraham NS, El-Serag HB, Johnson ML, et al. National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs. Gastroenterology 2005 Oct; 129(4): 1171–8PubMedCrossRefGoogle Scholar
  11. 11.
    Moore RA, Derry S, Phillips CJ, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice. BMC Musculoskelet Disord 2006; 7: 79PubMedCrossRefGoogle Scholar
  12. 12.
    Suh DC, Hunsche E, Shin HC, et al. Co-prescribing of proton pump inhibitors among chronic users of NSAIDs in the UK. Rheumatology (Oxford) 2008 Apr; 47(4): 458–63CrossRefGoogle Scholar
  13. 13.
    Goldstein JL, Howard KB, Walton SM, et al. Impact of adherence to concomitant gastroprotective therapy on nonsteroidal-related gastroduodenal ulcer complications. Clin Gastroenterol Hepatol 2006 Nov; 4(11): 1337–45PubMedCrossRefGoogle Scholar
  14. 14.
    Sturkenboom MC, Burke TA, Tangelder MJ, et al. Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2003 Dec; 18(11–12): 1137–47PubMedCrossRefGoogle Scholar
  15. 15.
    Abraham NS, Hartman C, Castillo D, et al. Effectiveness of national provider prescription of PPI gastroprotection among elderly NSAID users. Am J Gastroenterol 2008 Feb; 103(2): 323–32PubMedCrossRefGoogle Scholar
  16. 16.
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of non-steroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991 Nov 15; 115(10): 787–96PubMedGoogle Scholar
  17. 17.
    Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995 Aug 15; 123(4): 241–9PubMedGoogle Scholar
  18. 18.
    Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994 Mar 26; 343(8900): 769–72PubMedCrossRefGoogle Scholar
  19. 19.
    Lanas A, Ferrandez A. Inappropriate prevention of NSAID-induced gastrointestinal events among long-term users in the elderly. Drugs Aging 2007; 24(2): 121–31PubMedCrossRefGoogle Scholar
  20. 20.
    Lewis SC, Langman MJ, Laporte JR, et al. Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta-analysis based on individual patient data. Br J Clin Pharmacol 2002 Sep; 54(3): 320–6PubMedCrossRefGoogle Scholar
  21. 21.
    Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000 Nov 23; 343(21): 1520–8PubMedCrossRefGoogle Scholar
  22. 22.
    Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000 Sep 13; 284(10): 1247–55PubMedCrossRefGoogle Scholar
  23. 23.
    Langman MJ, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994 Apr 30; 343(8905): 1075–8PubMedCrossRefGoogle Scholar
  24. 24.
    La Corte R, Caselli M, Castellino G, et al. Prophylaxis and treatment of NSAID-induced gastroduodenal disorders. Drug Saf 1999 Jun; 20(6): 527–43PubMedCrossRefGoogle Scholar
  25. 25.
    Piper JM, Ray WA, Daugherty JR, et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991 May 1; 114(9): 735–40PubMedGoogle Scholar
  26. 26.
    Targownik LE, Thomson PA. Gastroprotective strategies among NSAID users: guidelines for appropriate use in chronic illness. Can Fam Physician 2006 Sep; 52(9): 1100–5PubMedGoogle Scholar
  27. 27.
    Vonkeman HE, van de Laar MA. Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention. Semin Arthritis Rheum 2010 Feb; 39(4): 294–312PubMedCrossRefGoogle Scholar
  28. 28.
    Sievert W, Stern AI, Lambert JR, et al. Low-dose antacids and nonsteroidal anti-inflammatory drug-induced gastropathy in humans. J Clin Gastroenterol 1991; 13(Suppl. 1): S145–8PubMedCrossRefGoogle Scholar
  29. 29.
    Singh G, Ramey DR, Morfeld D, et al. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis: a prospective observational cohort study. Arch Intern Med 1996 Jul 22; 156(14): 1530–6PubMedCrossRefGoogle Scholar
  30. 30.
    Agrawal NM, Roth S, Graham DY, et al. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer: a randomized, controlled trial. Ann Intern Med 1991 Aug 1; 115(3): 195–200PubMedGoogle Scholar
  31. 31.
    Stiel D, Ellard KT, Hills LJ, et al. Protective effect of enprostil against aspirin-induced gastroduodenal mucosal injury in man: comparison with cimetidine and sucralfate. Am J Med 1986 Aug 18; 81(2A): 54–8PubMedCrossRefGoogle Scholar
  32. 32.
    French PC, Darekar BS, Mills JG, et al. Ranitidine in the prevention of non-steroidal anti-inflammatory drug-associated gastric and duodenal ulceration in arthritic patients. European J Gastroenterol Hepatol 1994; 6(12): 1141–7CrossRefGoogle Scholar
  33. 33.
    Ehsanullah RS, Page MC, Tildesley G, et al. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. BMJ 1988 Oct 22; 297(6655): 1017–21PubMedCrossRefGoogle Scholar
  34. 34.
    Robinson M, Mills RJ, Euler AR. Ranitidine prevents duodenal ulcers associated with non-steroidal anti-inflammatory drug therapy. Aliment Pharmacol Ther 1991 Apr; 5(2): 143–50PubMedCrossRefGoogle Scholar
  35. 35.
    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 May 30; 334(22): 1435–9PubMedCrossRefGoogle Scholar
  36. 36.
    Bardhan KD, Bjarnason I, Scott DL, et al. The prevention and healing of acute non-steroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol. Br J Rheumatol 1993 Nov; 32(11): 990–5PubMedCrossRefGoogle Scholar
  37. 37.
    Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multi-centre, double-blind, placebo-controlled trial. Lancet 1988 Dec 3; 2(8623): 1277–80PubMedCrossRefGoogle Scholar
  38. 38.
    Graham DY, White RH, Moreland LW, et al. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group. Ann Intern Med 1993 Aug 15; 119(4): 257–62PubMedGoogle Scholar
  39. 39.
    Ekstrom P, Carling L, Wetterhus S, et al. Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy: a Nordic multicentre study. Scand J Gastroenterol 1996 Aug; 31(8): 753–8PubMedCrossRefGoogle Scholar
  40. 40.
    Bianchi Porro G, Lazzaroni M, Petrillo M, et al. Prevention of gastroduodenal damage with omeprazole in patients receiving continuous NSAIDs treatment: a double blind placebo controlled study. Ital J Gastroenterol Hepatol 1998 Feb; 30(1): 43–7PubMedGoogle Scholar
  41. 41.
    Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol 2006 Apr; 101(4): 701–10PubMedCrossRefGoogle Scholar
  42. 42.
    Pilotto A, Franceschi M, Leandro G, et al. Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2004 Nov 15; 20(10): 1091–7PubMedCrossRefGoogle Scholar
  43. 43.
    Cullen D, Bardhan KD, Eisner M, et al. Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users. Aliment Pharmacol Ther 1998 Feb; 12(2): 135–40PubMedCrossRefGoogle Scholar
  44. 44.
    Hawkey CJ. Progress in prophylaxis against nonsteroidal anti-inflammatory drug-associated ulcers and erosions. Omeprazole NSAID Steering Committee. Am J Med 1998 Mar 30; 104(3A): 67S–74S; discussion 9S-80SPubMedCrossRefGoogle Scholar
  45. 45.
    Desai JC, Sanyal SM, Goo T, et al. Primary prevention of adverse gastroduodenal effects from short-term use of non-steroidal anti-inflammatory drugs by omeprazole 20mg in healthy subjects: a randomized, double-blind, placebo-controlled study. Dig Dis Sci 2008 Aug; 53(8): 2059–65PubMedCrossRefGoogle Scholar
  46. 46.
    Bianchi Porro G, Imbesi V, Lazzaroni M. Pantoprazole vs placebo in prevention of NSAID-induced ulcers [abstract]. Gastroenterology 1998; 114: A74CrossRefGoogle Scholar
  47. 47.
    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 Jan 28; 162(2): 169–75PubMedCrossRefGoogle Scholar
  48. 48.
    Lanas A, Rodrigo L, Marquez JL, et al. Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole. Scand J Gastroenterol 2003 Jul; 38(7): 693–700PubMedCrossRefGoogle Scholar
  49. 49.
    Hoer A, Gothe H, Schiffhorst G, et al. Comparison of the effects of diclofenac or other non-steroidal anti-inflammatory drugs (NSAIDs) and diclofenac or other NSAIDs in combination with proton pump inhibitors (PPIs) on hospitalisation due to peptic ulcer disease. Pharmacoepidemiol Drug Saf 2007 Aug; 16(8): 854–8PubMedCrossRefGoogle Scholar
  50. 50.
    Lanas A, Garcia-Rodriguez LA, Arroyo MT, et al. Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 2007 Mar; 102(3): 507–15PubMedCrossRefGoogle Scholar
  51. 51.
    Vonkeman HE, Fernandes RW, van der Palen J, et al. Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study. Arthritis Res Ther 2007; 9(3): R52PubMedCrossRefGoogle Scholar
  52. 52.
    Jordan KM, Arden NK, Doherty M, et al. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis. Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2003 Dec; 62(12): 1145–55PubMedCrossRefGoogle Scholar
  53. 53.
    Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2005 May; 64(5): 669–81PubMedCrossRefGoogle Scholar
  54. 54.
    Zhang W, Doherty M, Leeb BF, et al. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007 Mar; 66(3): 377–88PubMedCrossRefGoogle Scholar
  55. 55.
    National Collaborating Centre for Chronic Conditions. Osteoarthritis: national clinical guideline for care and management in adults. 2008 [online]. Available from: http://www.nice.org.uk/nicemedia/pdf/CG059FullGuideline.pdf [Accessed 2009 Jul 13]
  56. 56.
    No authors listed. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000 Sep; 43 (9): 1905-15Google Scholar
  57. 57.
    Luqmani R, Hennell S, Estrach C, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of rheumatoid arthritis (after the first 2 years). Rheumatology (Oxford) 2009 Apr; 48(4): 436–9CrossRefGoogle Scholar
  58. 58.
    No authors listed. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002 Feb; 46 (2): 328-46Google Scholar
  59. 59.
    Bardou M, Vauzelle-Kervroedan F. Proton pump inhibition (PPI) significantly reduces gastrointestinal (GI) events associated with the highly ulcerogenic NSAID, ketoprofen: a French prescription survey. Marseille: Congress of the French Association of Pharmacology and Therapeutics, 2009Google Scholar
  60. 60.
    Davis R, Yarker YE, Goa KL. Diclofenac/misoprostol: a review of its pharmacology and therapeutic efficacy in painful inflammatory conditions. Drugs Aging 1995 Nov; 7(5): 372–93PubMedCrossRefGoogle Scholar
  61. 61.
    Geis GS. Overall safety of Arthrotec. Scand J Rheumatol Suppl. 1992; 96: 33–6PubMedCrossRefGoogle Scholar
  62. 62.
    Kiff PS, Stead H, Morant SV, et al. Arthrotec, diclofenac and ibuprofen in general practice. Eur J Rheumatol Inflamm 1994; 14(3 Suppl.): 31–8PubMedGoogle Scholar
  63. 63.
    Melo Gomes JA, Roth SH, Zeeh J, et al. Double-blind comparison of efficacy and gastroduodenal safety of diclofenac/misoprostol, piroxicam, and naproxen in the treatment of osteoarthritis. Ann Rheum Dis 1993 Dec; 52(12): 881–5PubMedCrossRefGoogle Scholar
  64. 64.
    Meda. Axorid: summary of product characteristics. 2010 [online]. Available from URL: http://www.medicines.org.uk/emc/medicine/22656/SPC/Axorid+modified-release+capsules/ [Accessed 2010 Nov 8]
  65. 65.
    Hochberg MC. NSAIDS: mechanisms and pathways of action. Hosp Pract (Off Ed) 1989 Mar 15; 24(3): 185–90, 95, 98Google Scholar
  66. 66.
    Kantor TG. Ketoprofen: a review of its pharmacologic and clinical properties. Pharmacotherapy 1986 May–Jun; 6(3): 93–103PubMedGoogle Scholar
  67. 67.
    Veys EM. 20 years' experience with ketoprofen. Scand J Rheumatol Suppl. 1991; 90: 1–44PubMedCrossRefGoogle Scholar
  68. 68.
    Williams RL, Upton RA. The clinical pharmacology of ketoprofen. J Clin Pharmacol 1988 Dec; 28(12 Suppl.): S13–22PubMedGoogle Scholar
  69. 69.
    Folco G, Borghi C, Berti F. Non-steroidal antiinflammatory drug therapy: advantages and disadvantages of long half-life drugs versus slow-release formulations. Int J Clin Pharmacol Res 1986; 6(6): 475–80PubMedGoogle Scholar
  70. 70.
    Morley KD, Bernstein RM, Hughes GR, et al. A comparative trial of a controlled-release formulation of ketoprofen ('Oruvail') and a conventional capsule formulation of ketoprofen ('Orudis') in patients with osteoarthritis of the hip. Curr Med Res Opin 1984; 9(1): 28–34PubMedCrossRefGoogle Scholar
  71. 71.
    Dreiser RL, Riebenfeld D. Nimesulide in the treatment of osteoarthritis: double-blind studies in comparison with piroxicam, ketoprofen and placebo. Drugs 1993; 46Suppl. 1: 191–5PubMedCrossRefGoogle Scholar
  72. 72.
    Leopold M. A double-blind cross-over comparative study of ketoprofen versus naproxen in the treatment of osteoarthritis of the knee [abstract]. Scand J Gastroenterol 1980; 33: 45Google Scholar
  73. 73.
    Hossain MA. Comparison of the efficacy and tolerability of ketoprofen (Oruvail) 200 mg once daily with indo-methacin (Indocid R) 75 mg twice daily in osteoarthritis of the knee and hip: a double-blind, within-patient, randomized trial. Clinical Trial Journal 1990; 27: 268–77Google Scholar
  74. 74.
    Gyory AN, Bloch M, Burry HC, et al. Orudis in management of rheumatoid arthritis and osteoarthrosis of the hip: comparison with indomethacin. Br Med J 1972 Nov 18; 4(5837): 398–400PubMedCrossRefGoogle Scholar
  75. 75.
    Bresnihan FP, Grahame R, Burry HC. Ketoprofen in the management of osteoarthrosis of the hip: comparison with phenylbutazone. Rheumatol Rehabil 1974 Aug; 13(3): 125–31PubMedCrossRefGoogle Scholar
  76. 76.
    Cardoe N. Double-blind cross-over study of ketoprofen and phenylbutazone in patients with chronic osteoarthrosis of the hip. Rheumatol Rehabil 1976; Suppl: 27-33Google Scholar
  77. 77.
    Lang E, Steger W. A comparative study of efficacy and tolerability of ketoprofen and piroxicam [abstract]. Br J Clin Pract 1981 Jul–Aug; 35(7–8): 267PubMedGoogle Scholar
  78. 78.
    Bendix T, Schmidt I, Rasmussen K, et al. Diclofenac (Voltaren) and ketoprofen (Orudis) in rheumatoid arthritis: a randomized double-blind multicentre trial. Curr Ther Res 1983; 33: 192–9Google Scholar
  79. 79.
    Boey ML, Rae S, Feng PH. Comparison of efficacy of and tolerance to ketoprofen and diclofenac sodium in the treatment of rheumatoid arthritis. Singapore Med J 1988 Jun; 29(3): 240–5PubMedGoogle Scholar
  80. 80.
    Wollheim FA, Lindroth Y, Sjoblom KG. A comparison of ketoprofen and naproxen in rheumatoid arthritis. Rheumatol Rehabil 1978 Suppl.: 78-83Google Scholar
  81. 81.
    Martin-Mola E, Gijon-Banos J, Ansoleaga JJ. Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis. Rheumatol Int 1995; 15(3): 111–6PubMedCrossRefGoogle Scholar
  82. 82.
    Jalava S, Junnila SYT. Double-blind cross-over study of piroxicam (Felden) and ketoprofen (Orudis) in rheumatoid arthritis. Scand J Rheumatol 1986; 16: 68–9Google Scholar
  83. 83.
    El-Ghobarey AF, Rennie JA, Hadidi T, et al. A comparative trial of large doses of ketoprofen and indomethacin in the treatment of rheumatoid arthritis. Curr Med Res Opin 1976; 4(6): 432–5PubMedCrossRefGoogle Scholar
  84. 84.
    Fossgreen J, Kirchheiner B, Petersen FO, et al. Clinical evaluation of ketoprofen (19.583 R.P.) in rheumatoid arthritis: double-blind cross-over comparison with indomethacin. Scand J Rheumatol Suppl. 1976; 1976(0): 93–8PubMedGoogle Scholar
  85. 85.
    Uddenfeldt P, Leden I, Rubin B. A double-blind comparison of oral ketoprofen ‘controlled release’ and indomethacin suppository in the treatment of rheumatoid arthritis with special regard to morning stiffness and pain on awakening. Curr Med Res Opin 1993; 13(3): 127–32PubMedCrossRefGoogle Scholar
  86. 86.
    Peltola P. A double-blind cross-over study of ketoprofen and phenylbutazone in rheumatoid arthritis. Scand J Rheumatol 1976 Suppl.; 14: 111–3Google Scholar
  87. 87.
    Vignon E, Courcier S, Laborde C, et al. LP 200 mg flurbiprofen versus LP 200 mg ketoprofen in rheumatoid arthritis in rheumatologic practice. Rev Rhum Ed Fr 1993 Jul–Sep; 60(7–8): 530–5PubMedGoogle Scholar
  88. 88.
    Mills SB, Bloch M, Bruckner FE. Double-blind cross-over study of ketoprofen and ibuprofen in management of rheumatoid arthritis. Br Med J 1973 Oct 13; 4(5884): 82–4PubMedCrossRefGoogle Scholar
  89. 89.
    Montrone F, Fumagalli M, Pellegrini P, et al. A double-blind cross-over evaluation of ketoprofen (Orudis) and ibuprofen in the management of rheumatoid arthritis. Rheumatol Rehabil 1979 May; 18(2): 114–8PubMedCrossRefGoogle Scholar
  90. 90.
    Calin A, Bennett RM, Sukhupunyaraksa S, et al. Double-blind, multi-centre parallel trial of ketoprofen and ibuprofen in the treatment of rheumatoid arthritis. J Rheumatol 1977; 4(2): 153–7PubMedGoogle Scholar
  91. 91.
    Saxena RP, Saxena U. A comparative trial of ketoprofen and ibuprofen in patients with rheumatic disease. Curr Med Res Opin 1978; 5(6): 484–8PubMedCrossRefGoogle Scholar
  92. 92.
    Ahern MJ, Wetherall M, Leslie A, et al. A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis. Br J Clin Pract 1992; 46(4): 229–33PubMedGoogle Scholar
  93. 93.
    Jessop JD. Double-blind study of ketoprofen and phenylbutazone in ankylosing spondylitis. Rheumatol Rehabil 1976 Suppl.: 37-42Google Scholar
  94. 94.
    Treadwell BL, Tweed JM. Ketoprofen (Orudis) in ankylosing spondylitis. N Z Med J 1975 May 14; 81(539): 411–3PubMedGoogle Scholar
  95. 95.
    Renier JC, Fournier M, Loyau G, et al. Ankylosing spondylitis: comparative trial of two non-steroidal anti-inflammatory agents — pirprofen and ketoprofen. Nouv Presse Med 1982 Aug 28; 11(33): 2494–6PubMedGoogle Scholar
  96. 96.
    Toft B, Christophersen J, Christensen N, et al. A double-blind, crossover study of a sustained-release tablet of ketoprofen and normal ketoprofen capsules in the treatment of patients with osteoarthritis. Curr Med Res Opin 1985; 9(10): 708–12PubMedCrossRefGoogle Scholar
  97. 97.
    Teule M. Double-blind comparative multicenter study of the efficacy and safety of a slow-release tablet of 200 mg ketoprofen and a 50 mg ketoprofen capsule four times daily. Curr Ther Res 1986; 40: 1129–46Google Scholar
  98. 98.
    Caldwell JR, Germain BF, Lourie SH, et al. Ketoprofen versus indomethacin in patients with rheumatoid arthritis: a multicenter double blind comparative study. J Rheumatol 1988 Oct; 15(10): 1476–9Google Scholar
  99. 99.
    Schumacher Jr HR. Ketoprofen extended-release capsules: a new formulation for the treatment of osteoarthritis and rheumatoid arthritis. Clin Ther 1994 Mar–Apr; 16(2): 145–59PubMedGoogle Scholar
  100. 100.
    AstraZeneca. Losec capsules 10mg, 20mg and 40mg: summary of Product Characteristics. 2008Google Scholar
  101. 101.
    Andersson T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors: focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokinet 1996 Jul; 31(1): 9–28PubMedCrossRefGoogle Scholar
  102. 102.
    Hawkey CJ, Karrasch JA, Szczepanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) study group. N Engl J Med 1998 Mar 12; 338(11): 727–34PubMedCrossRefGoogle Scholar
  103. 103.
    Yeomans ND, Tulassay Z, Juhasz L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) study group. N Engl J Med 1998 Mar 12; 338(11): 719–26PubMedCrossRefGoogle Scholar
  104. 104.
    Moore A, Bjarnason I, Cryer B, et al. Evidence for endoscopic ulcers as meaningful surrogate endpoint for clinically significant upper gastrointestinal harm. Clin Gastroenterol Hepatol 2009 Nov; 7(11): 1156–63PubMedCrossRefGoogle Scholar
  105. 105.
    Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001 Mar 29; 344(13): 967–73PubMedCrossRefGoogle Scholar
  106. 106.
    Targownik LE, Metge CJ, Leung S, et al. The relative efficacies of gastroprotective strategies in chronic users of nonsteroidal anti-inflammatory drugs. Gastroenterology 2008 Apr; 134(4): 937–44PubMedCrossRefGoogle Scholar
  107. 107.
    Garcia Rodriguez LA, Ruigomez A. Secondary prevention of upper gastrointestinal bleeding associated with maintenance acid-suppressing treatment in patients with peptic ulcer bleed. Epidemiology 1999 May; 10(3): 228–32PubMedCrossRefGoogle Scholar
  108. 108.
    Laine L, Curtis SP, Cryer B, et al. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2007 Feb 10; 369(9560): 465–73PubMedCrossRefGoogle Scholar
  109. 109.
    Ethypharm. Data on file: clinical study report KEO/25004/001, 2006Google Scholar
  110. 110.
    Ethypharm. Data on file: clinical study report KEO/25004/002, 2008Google Scholar

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Authors and Affiliations

  1. 1.Clinical Orthopaedics-Department of Molecular Pathology and Innovative TherapiesPolytechnic University of MarcheAnconaItaly
  2. 2.Meda Pharmaceuticals, Parque E. San Fernando, Edif. BerlínMadridSpain

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