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Azathioprine, 6-MP

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Summary

Azathioprine is an antimetabolite drug used as an immunosuppressive to prevent organ rejection after transplant and to treat steroid-refractory inflammatory conditions. Azathioprine is activated to become 6-MP, which is then further metabolized by HGPRT to form purine analogs that can be incorporated into DNA and RNA and terminate synthesis. 6-MP is degraded by xanthine oxidase, and xanthine oxidase is inhibited by the gout drugs allopurinol and febuxostat. Therefore, gout patients taking azathioprine along with one of those medications can have 6-MP buildup to toxic levels. Additionally, patients on azathioprine may develop myelosuppression and GI and liver toxicity. 

Key Points

  • Azathioprine / 6-MP
    • Mechanism
      • Purine analog
        • Activated by HGPRT
          • Azathioprine → 6-MP → [HGPRT] 6-TGNs
        • Degraded by xanthine oxidase
          • 6-MP → [XO] degradation
    • Clinical Use
      • Immunosuppression
        • Can be used to prevent organ rejection
      • Inflammatory conditions such as RA, IBD, SLE
        • Used to take patients off steroids in chronic disease and to treat steroid-refractory chronic disease
    • Adverse effects
      • Allopurinol and febuxostat increase toxicity
        • 6-MP is degraded by xanthine oxidase, which these drugs inhibit
      • Pancreatitis
      • Myelosuppression (obvious / non-specific)
      • GI and liver toxicity (non-specific)