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Pharmacology and side effects of azathioprine when used in rheumatic diseases

H Michael Belmont, MD
Section Editor
Daniel E Furst, MD
Deputy Editor
Paul L Romain, MD


Azathioprine (AZA) is the 1-methyl-4-nitro-5-imidazolyl derivative of thioguanine, a purine mimic antimetabolite [1]. Its synthesis evolved from the same antibiotic and purine antimetabolite research in the late 1940s that led to the discovery and subsequent development of allopurinol and acyclovir [1].

In addition to its use in preventing transplant rejection, AZA became available for use in the treatment of rheumatoid arthritis (RA) in patients who had not responded to less aggressive therapy. Use in RA was the indication that constituted the bulk of its use in the rheumatic diseases before leflunomide and biologic agents became available for the treatment of RA in the late 1990s and early 2000s. AZA has subsequently also been used for the treatment of psoriatic arthritis, psoriasis, reactive arthritis, Behçet’s syndrome, polymyositis, and systemic lupus erythematosus (SLE), and it has been used to sustain remissions in systemic vasculitis.

The pharmacology of AZA, the side effects associated with its use, and the efficacy of AZA in the management of RA will be reviewed here. The role of AZA in the management of the different rheumatic diseases and of transplant recipients is presented in detail separately on the appropriate topic reviews.


Azathioprine (AZA) is well-absorbed from the gastrointestinal tract. It has a serum half-life of 0.2 to 0.5 hours, resulting in a biologic half-life of approximately 24 hours [2]. AZA is a prodrug; the action of glutathione in red blood cells causes the formation of the principal metabolite, 6-mercaptopurine (6-MP) [1].

Metabolism — The prodrug AZA is approximately 30 percent protein-bound. Forty-five percent of the drug is excreted in the urine; the remainder is metabolized to 6-MP, which is then further metabolized along competing routes:


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Literature review current through: Jul 2017. | This topic last updated: Mar 28, 2017.
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