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Cyclophosphamide, Ifosfamide

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Summary

Cyclophosphamide and ifosfamide are alkylating agents that crosslink DNA, interfering with replication and transcription. Used as a chemotherapy and for treating autoimmune diseases, these drugs require bioactivation in the liver in order to function. Important adverse effects to know include Fanconi syndrome and hemorrhagic cystitis, the latter of which can be prevented by the administration of mesna.

Key points

  • Cyclophosphamide, ifosfamide
    • Mechanism
      • Alkylating agents that crosslink DNA
        • Requires bioactivation by the liver (by P450 enzyme) 
    • Clinical Use
      • Non-Hodgkin’s lymphomas
      • Solid tumors
        • Breast and ovarian cancer
      • Rheumatic disease
        • E.g. SLE, granulomatosis with polyangiitis 
    • Adverse Effects
      • Hemorrhagic cystitis
        • Can be prevented with mesna, which binds acrolein, a toxic metabolite of cyclophosphamide 
        • Can also cause bladder cancer
      • Myelosuppression (nonspecific)
      • Fanconi syndrome
        • Caused by ifosfamide