Pharmacology and side effects of azathioprine when used in rheumatic diseases
- H Michael Belmont, MD
H Michael Belmont, MD
- Professor of Medicine
- NYU School of Medicine
- Section Editor
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Clinical professor, University of Washington, Seattle
- Clinical professor, University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific Arthritis Associates
Azathioprine (AZA) is an immunosuppressive agent that acts through its effects as an antagonist of purine metabolism, resulting in the inhibition of DNA, RNA, and protein synthesis. It has been used as an immunosuppressive agent for the treatment of a variety of disorders, including a number of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis and polymyositis, systemic sclerosis, and systemic vasculitis; for the treatment of inflammatory bowel disease and other conditions; and for the prevention of organ transplant rejection.
The pharmacology and adverse effects of AZA, particularly when used in the context of the rheumatic diseases, will be reviewed here. The role of AZA in the management of the different rheumatic diseases and other autoimmune and immune-mediated disorders, and for the prevention and management of transplant rejection, is presented in detail separately in the appropriate topic reviews covering the treatment of these individual conditions.
Azathioprine (AZA) is the 1-methyl-4-nitro-5-imidazolyl derivative of thioguanine, a purine-mimic antimetabolite . It is well-absorbed from the gastrointestinal tract and has a serum half-life of 0.2 to 0.5 hours, resulting in a biologic half-life of approximately 24 hours . AZA is a prodrug; the action of glutathione in red blood cells causes the formation of the principal metabolite 6-mercaptopurine (6-MP) .
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:
●It undergoes catabolic oxidation to 6-thiouric acid, which is an inactive metabolite. This reaction is catalyzed by xanthine oxidase, which is concentrated in the intestine and liver.
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- Pharmacogenetics and TPMT testing
- Drug interactions
- - Xanthine oxidase inhibitors
- - Other medications
- MECHANISM OF ACTION
- ADVERSE EFFECTS
- Gastrointestinal problems
- Bone marrow suppression
- DOSING AND MONITORING
- SUMMARY AND RECOMMENDATIONS