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

Aim-We evaluated the effect of coadministration. of sulphasalazine, mesalam ine, and balsalazide on the pharmacokinetics and pharmacodynamics of azathi oprine 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 gr oup drug interaction study and treated with mesalamine 4 g/day, sulphasalaz ine 4 g/day, or balsalazide 6.75 g/day. The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined se parately as total leucocyte counts < 3.0 x 10(9)/l and less than or equal t o 3.5 x 10(9)/l. Whole blood 6-thioguanine nucleotide concentrations were d etermined. Results-Three patients could not be evaluated for the primary outcome measu re. 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. Ther e were significant increases mi mean whole blood 6-thioguanine nucleotide c oncentrations from baseline at most time points, in the mesalamine and sulp hasalazine groups but not in the balsalazide group. Conclusions-In patients with Crohn's disease receiving azathioprine or 6-me rcaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide results in an increase in whole blood 6-thinguanine, nucleotide , concentrations and a high frequency of leucopenia.