Rheumatology Question 27 Instructor

Cyclophosphamide is an alkylating agent that crosslinks DNA so that it cannot replicate, resulting in double stranded DNA breaks. It is cytotoxic to resting and dividing lymphocytes, and acts to suppress primary cellular and humoral immune responses. It is considered to be one of the most potent immunosuppressive drugs available.

List four side effects associated with cyclophosphamide use. Are there ways to minimize cyclophosphamide toxicity?

The toxicity profile of cyclophosphamide includes:

  • Infections, including unusual or opportunistic infections such as PCP, nocardia and TB.
  • Malignancies, including leukemia, skin and bladder cancer
  • Gonadal toxicity in men and women
  • Myelosuppression (mostly leucopenia and neutropenia)
  • Hemorrhagic cystitis
  • Nausea
  • Alopecia

Methods of minimizing toxicity include:

  • Minimizing the duration of therapy
  • Avoiding night time doses (This reduces duration of bladder exposure to the toxic metabolite acrolein and thus reduces risk of hemorrhagic cystitis.)
  • Forced diuresis (Drinking 8 glasses of water/day)
  • Intermittent IV pulse therapy rather than daily oral therapy
  • Using MESNA (sodium 2-mercaptoethane sulfonate). This inactivates the toxic metabolite acrolein in the urine, thereby protecting the bladder from its effects. Acrolein is responsible for causing hemorrhagic cystitis and bladder cancer.

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