Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide

P. W. Lowry, C. L. Franklin, A. L. Weaver, C. L. Szumlanski, D. C. Mays, E. V. Loftus, W. J. Tremaine, J. J. Lipsky, R. M. Weinshilboum, W. J. Sandborn

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182 Scopus citations

Abstract

Aim - We evaluated the effect of coadministration of sulphasalazine, mesalamine, and balsalazide on the pharmacokinetics and pharmacodynamics of azathioprine and 6-mercaptopurine. Methods - Thirty four patients with Crohn's disease receiving azathioprine or 6-mercaptopurine were enrolled in an eight week non-randomised parallel group drug interaction study and treated with mesalamine 4 g/day, sulphasalazine 4 g/day, or balsalazide 6.75 g/day. The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined separately as total leucocyte counts <3.0 × 109/1 and ≤3.5×109/1. Whole blood 6-thioguanine nucleotide concentrations were determined. Results -Three patients could not be evaluated for the primary outcome measure. In the remaining 31 patients, the frequency of total leucocyte counts <3.0 and ≤3.5 were: 1/10 and 5/10 in the mesalamine group; 1/11 and 6/11 in the sulphasalazine group; and 0/10 and 2/10 in the balsalazide group. There were significant increases in mean whole blood 6-thioguanine nucleotide concentrations from baseline at most time points in the mesalamine and sulphasalazine groups but not in the balsalazide group. Conclusions - In patients with Crohn's disease receiving azathioprine or 6-mercaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide results in an increase in whole blood 6-thioguanine nucleotide concentrations and a high frequency of leucopenia.

Original languageEnglish (US)
Pages (from-to)656-664
Number of pages9
JournalGut
Volume49
Issue number5
DOIs
StatePublished - 2001

Keywords

  • 6-mercaptopurine
  • Azathioprine
  • Balsalazide
  • Inflammatory bowel disease
  • Leucopenia
  • Mesalamine
  • Sulphasalazine

ASJC Scopus subject areas

  • Gastroenterology

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    Lowry, P. W., Franklin, C. L., Weaver, A. L., Szumlanski, C. L., Mays, D. C., Loftus, E. V., Tremaine, W. J., Lipsky, J. J., Weinshilboum, R. M., & Sandborn, W. J. (2001). Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut, 49(5), 656-664. https://doi.org/10.1136/gut.49.5.656