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

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 x 10(9)/l and < or = 3.5 x 10(9)/l. 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 < or = 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.

• Authors: 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
• Journal: Gut (Gut) Vol. 49 Issue 5 Pg. 656-64 (Nov 2001) ISSN: 0017-5749 [Print] England
• PMID: 11600468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aminosalicylic Acids
• Anti-Inflammatory Agents, Non-Steroidal
• Immunosuppressive Agents
• Phenylhydrazines
• Sulfasalazine
• Mesalamine
• Mercaptopurine
• Methyltransferases
• Thioguanine
• Azathioprine
• balsalazide

Topics

• Adult
• Aminosalicylic Acids (adverse effects)
• Analysis of Variance
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects)
• Azathioprine (adverse effects)
• Binomial Distribution
• Chromatography, High Pressure Liquid
• Confidence Intervals
• Drug Interactions
• Female
• Humans
• Immunosuppressive Agents (adverse effects)
• Leukopenia (chemically induced, metabolism)
• Male
• Mercaptopurine (adverse effects)
• Mesalamine (adverse effects)
• Methyltransferases (blood)
• Phenylhydrazines
• Sulfasalazine (adverse effects)
• Thioguanine (analysis)