Allopurinol/Febuxostat

Summary

Allopurinol and febuxostat are drugs used to reduce uric acid levels in order to treat gout. These drugs are inhibitors of xanthine oxidase, which decreases uric acid production. This decrease in uric acid can be used to treat primary hyperuricemia and gout, as well as high uric acid levels resulting from secondary causes, such as tumor lysis syndrome after chemotherapy. Notably, allopurinol and febuxostat increase the levels of azathioprine and 6-mercaptopurine to cause toxicity, since these drugs are broken down in part by xanthine oxidase. Other side effects to note include drug rashes like steven johnson syndrome, and hepatotoxicity with use of febuxostat.

Key Points

• Allopurinol and Febuxostat
  • Mechanism
    • Competitive inhibition of Xanthine Oxidase
      • decreased production of urate → decreased uric acid
  • Clinical Use
    • Hyperuricemic states
      • Chronic Gout
        • Gout is a type of arthritis. It occurs when uric acid builds up in blood and causes inflammation in the joints. Acute gout is a painful condition that often affects only one joint. Chronic gout is the repeated episodes of pain and inflammation (wiki). (Script)
      • Tumor Lysis Syndrome
        • Allopurinol is also used as pre-treatment in lymphoma and leukemia to prevent tumor lysis syndrome (mictlan, MB). (script)
  • Adverse Effects
    • ↑ azathioprine and 6-mercaptopurine (MP)
      • both are metabolized by xanthine oxidase - can lead to toxicity if taken together
      • Interaction may be used to amplify azathioprine's immunosuppressive effect while reducing its dose, but unrecognized, can lead to severe immunosuppression
    • Allopurinol may cause drug rash or Stevens-Johnson Syndrome
      • Allopurinol is a hapten, a small molecule that binds to bigger carriers and triggers a hypersensitivity reaction. Does not elicit an immune reaction on its own (mictlan). (script)
      • May also cause DRESS syndrome
    • Febuxostat may cause hepatotoxicity