Drug Safety

, Volume 25, Issue 7, pp 537–544 | Cite as

Renal Failure Associated with the Use of Celecoxib and Rofecoxib

  • Syed R. AhmadEmail author
  • Cindy Kortepeter
  • Allen Brinker
  • Min Chen
  • Julie Beitz
Original Research Article


Objective: Celecoxib and rofecoxib are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclo-oxygenase-2 (COX-2) isoenzyme at therapeutic concentrations. The nephrotoxic potential of selective COX-2 inhibitors has not been clearly established. This study was conducted in order to understand the association between acute renal failure and the two COX-2 inhibitors celecoxib and rofecoxib.

Methods: A search was performed in the US Food and Drug Administration’s (FDA) Adverse Event Reporting System (AERS) to identify cases of renal failure submitted to the FDA. A MEDLINE search of the English language literature was also performed to identify published cases of renal failure associated with celecoxib and rofecoxib.

Results: One hundred twenty-two and 142 domestic US cases of celecoxib and rofecoxib-associated renal failure, respectively, were identified in the AERS database. The literature search identified 19 cases of acute renal impairment in association with celecoxib and rofecoxib. In addition, drug regulatory authorities in the UK, Canada, and Australia have received about 50 reports of renal failure with celecoxib and rofecoxib. Descriptive statistics of the AERS cases have been summarised in this report.

Conclusions: Data from AERS and published case reports suggest that use of both these drugs is associated with renal effects similar to that of conventional nonselective NSAIDs. Physicians should be aware that serious or life-threatening renal failure has been reported in patients with normal or impaired renal function after short-term therapy with celecoxib and rofecoxib. Patients at greatest risk for renal injury are those with pre-existing renal impairment, heart failure, liver dysfunction, those taking diuretics and/or ACE inhibitors, and the elderly. Kidney function should be monitored closely for any signs of potential renal injuries soon after initiating treatment with these agents, especially in high-risk populations. In addition, healthcare practitioners should adequately warn patients of the signs and symptoms of serious renal toxicity, and of the need for them to see their physician promptly if they occur. Celecoxib and rofecoxib are not recommended for use in patients with advanced renal disease.


Acute Renal Failure Celecoxib Blood Urea Nitrogen Rofecoxib Adverse Event Reporting System 
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 authors acknowledge the many physicians, pharmacists, nurses, consumers and other reporters who submitted adverse event reports to the FDA directly or through the pharmaceutical manufacturers that formed the basis of this review.

The views expressed herein are those of the authors and do not necessarily imply endorsement from, nor represent the views of the Food and Drug Administration or the US Government.


  1. 1.
    Noble SL, King DS, Olutade JI. Cyclooxygenase-2 enzyme inhibitors: place in therapy. Am Fam Physician 2000; 61: 3669–76PubMedGoogle Scholar
  2. 2.
    FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345: 433–42PubMedCrossRefGoogle Scholar
  3. 3.
    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. JAMA 2000; 284: 1247–55PubMedCrossRefGoogle Scholar
  4. 4.
    Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 1520–8PubMedCrossRefGoogle Scholar
  5. 5.
    Brinker AD, Bonnel RA, Feight AG, et al. Celecoxib and rofecoxib. J Am Dent Assoc 2001 Nov; 132: 1502–4PubMedGoogle Scholar
  6. 6.
    Stichtenoth DO, Frolich JC. COX-2 and the kidneys. Curr Pharm Des 2000; 6: 1737–53PubMedCrossRefGoogle Scholar
  7. 7.
    Swan SK, Rudy DW, Lasseter KC, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet: a randomized, controlled trial. Ann Intern Med 2000; 133: 1–9PubMedGoogle Scholar
  8. 8.
    Rossat J, Maillard M, Nussberger J, et al. Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects. Clin Pharmacol Ther 1999; 66: 76–84PubMedCrossRefGoogle Scholar
  9. 9.
    Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med 1999; 107: 65S–71SPubMedCrossRefGoogle Scholar
  10. 10.
    Kromers R, Anderson S, Epstein M. Renal and cardiovascular effects of selective cyclooxygenase-2 inhibitors. Am J Kidney Dis 2001; 38: 1145–57CrossRefGoogle Scholar
  11. 11.
    Brown EG, Wood L, Wood S. The medical dictionary for regulatory activities (MedDRA). Drug Saf 1999; 20: 109–17PubMedCrossRefGoogle Scholar
  12. 12.
    Graham MG. Acute renal failure related to high-dose celecoxib. Ann Intern Med 2001; 135: 69–70PubMedGoogle Scholar
  13. 13.
    Rocha JL, Fernandez-Alonso J. Acute tululointerstitial nephritis associated with the selective COX-2 enzyme inhibitor, rofecoxib. Lancet 2001; 357: 1946–7PubMedCrossRefGoogle Scholar
  14. 14.
    Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med 2001; 111: 64–7PubMedCrossRefGoogle Scholar
  15. 15.
    Ofran Y, Bursztyn M, Ackerman Z. Rofecoxib-induced renal dysfunction in a patient with compensated cirrhosis and heart failure. Am J Gastroenterol 2001; 96: 1941PubMedCrossRefGoogle Scholar
  16. 16.
    Wolf G, Porth J, Stahl RAK. Acute renal failure associated with rofecoxib. Ann Intern Med 2000; 133: 394PubMedGoogle Scholar
  17. 17.
    Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis 2000; 35: 937–40PubMedCrossRefGoogle Scholar
  18. 18.
    Braden GL, O’Shea M, Mulhern J, et al. COX-2 inhibitor acute renal failure: association with hyperkalemia and type IV renal tubular acidosis [abstract]. J Am Soc Nephrol 2000; 11: 126AGoogle Scholar
  19. 19.
    Stafford C, Bestosos JT. Celecoxib-induced acute renal failure [abstract]. J Am Soc Nephrol 2000; 11: 134AGoogle Scholar
  20. 20.
    Alkhuja S, Menkel RA, Alwarshetty M, et al. Celecoxib-induced nonoliguric acute renal failure. Ann Pharmacother 2002; 36: 52–4PubMedCrossRefGoogle Scholar
  21. 21.
    Henao J, Hisamuddin I, Nzerue CM, et al. Celecoxib-induced acute interstitial nephritis. Am J Kidney Dis 2002; 39: 1313–7PubMedCrossRefGoogle Scholar
  22. 22.
    Stienburg KL. Rofecoxib (Vioxx): a year in review. Canadian ADR Newsletter 2001; 11: 4–7Google Scholar
  23. 23.
    McMorran M, Morawiecka I. Celecoxib (Celebrex): 1 year later. Canadian ADR Newsletter 2000; 10: 2–5Google Scholar
  24. 24.
    Adverse Drug Reactions Advisory Committee. Celecoxib: early Australian reporting experience. Australian ADRs Bulletin 2000; 19: 6Google Scholar
  25. 25.
    Committee on Safety of Medicines and the Medicines Control Agency. Rofecoxib (Vioxx). Curr Probl Pharmacovigilance 2000; 26: 13Google Scholar
  26. 26.
    Griffin MR, Yared A, Ray WA. Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 2000; 151: 488–96PubMedCrossRefGoogle Scholar
  27. 27.
    Sandler DP, Burr R, Weinberg CR. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease. Ann Intern Med 1991; 115: 165–72PubMedGoogle Scholar
  28. 28.
    Gurwitz JH, Avorn J, Ross-Degnan D, et al. Nonsteroidal anti-inflammatory drug-associated azotemia in the very old. JAMA 1990; 264: 471–5PubMedCrossRefGoogle Scholar
  29. 29.
    Whelton A. Renal aspects of treatment with conventional nonsteroidal anti-inflammatory drugs versus cyclooxygenase-2-specific inhibitors. Am J Med 2001; 110: 33S–42SPubMedCrossRefGoogle Scholar
  30. 30.
    Stillman MT, Schlesinger PA. Nonsteroidal anti-inflammatory drug nephrotoxicity: should we be concerned? Arch Intern Med 1990; 150: 268–70PubMedCrossRefGoogle Scholar
  31. 31.
    Whelton A, Hamilton CW. Nonsteroidal antiinflammatory drugs: effects on kidney function. J Clin Pharmacol 1991; 31: 588–9PubMedGoogle Scholar
  32. 32.
    Dunn MJ. Are COX-2 selective inhibitors nephrotoxic. Am J Kidney Dis 2000; 35: 976–7PubMedCrossRefGoogle Scholar
  33. 33.
    Noroian G, Clive D. Cyclo-oxygenase-2 inhibitors and the kidney: a case for caution. Drug Saf 2002; 25(3): 165–72PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Syed R. Ahmad
    • 1
    Email author
  • Cindy Kortepeter
    • 1
  • Allen Brinker
    • 1
  • Min Chen
    • 1
  • Julie Beitz
    • 1
  1. 1.Division of Drug Risk EvaluationOffice of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, HDF-430, Room 15B-08RockvilleUSA

Personalised recommendations