Azathioprine, 6-MP

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)