Cyclophosphamide (Cytoxan)

•  Cyclophosphamide is a cyclic phosphamide ester of mechlorethamine. It is transformed via hepatic and intracellular enzymes to active alkylating metabolites, acrolein and phosphoramide mustard. Cyclophosphamide causes prevention of cell division primarily by cross-linking DNA strands. It is considered to be cell cycle phase-nonspecific.

• Most commonly: nausea/vomiting, bone marrow suppression, reversible alopecia, anorexia

• Hemorrhagic cystitis results from direct bladder contact with cyclophosphamide metabolites and may be minimized with hydration and frequent voiding. May occur during or several months after treatment

• catheter bladder drainage, bladder irrigation, hyperhydration, forced diuresis and the administration of mesna. However, hyperhydration places the patient at risk for fluid overload and electrolyte imbalance, particularly given the antidiuretic effect of cyclophosphamide. It appears that mesna and hyperhydration are equally effective in preventing cyclophosphamide-induced cystitis in the BMT population.

• Interstitial pneumonitis and pulmonary fibrosis occur occasionally

• Administration of cyclophosphamide in doses higher than 30-40 mg/kg has been associated with water retention and dilutional hyponatremia. Children may be especially susceptible

• Cardiac toxicity (hemorrhagic necrosis) can occur, especially with high doses used in preparing patients for marrow transplantation (>120 mg/kg) and concomitant doxorubicin or daunorubicin therapy or with radiation to cardiac vessels or heart.