Cyclophosphamide Cytoxan

Action

Alkylating agent. Interferes with nucleic acids and proteins by cross-linking intracellular macromolecules. Cyclophosphamide (CTX) can inhibit secondary immune responses.

Selected Indications

Severe RA, SLE, vasculitis, interstitial lung disease. Metabolism

Well absorbed from gastrointestinal tract. It requires activation by liver to produce active metabolites. Unchanged drug and metabolites are excreted in the urine. Adverse Reactions

Bone marrow depression, primarily of white cell series, and predisposition to infection, both of which may be life-threatening but reversible with discontinuation of drug. Alopecia, drug-induced infertility with amenorrhea or defective spermatogenesis, hemorrhagic cystitis (in up to 25% of patients), fibrosing cystitis, carcinoma of the bladder, hematopoietic malignancies, anorexia, nausea, vomiting, and pulmonary fibrosis. Antidiuretic hormone-like activity may occur with large doses and result in hyponatremia.

Caution

Contraindicated in pregnant women and patients with hepatic impairment. Dosage requires adjustment in renal insufficiency. Frequent complete blood cell counts, platelet counts, and urinalyses must be obtained. Maintenance of high urine output and the use of 2-mercaptoethane sulfonate may reduce bladder complications.

Supply

Tablets, 25 and 50 mg; vials, 100, 200, and 500 mg for IV injection. Dosage

Oral route: 0.5 to 3.5 mg/kg daily given as single morning dose. IV route: For treatment of diffuse proliferative glomerulonephritis associated with SLE or systemic vasculitides, begin with monthly IV treatments at an initial dose of 0.5 mg/m2 Doses are then increased by 25% if the 7- to 10-day post-CTX white blood cell count is above 5,000/mL or decreased by 25% if that white blood cell count is below 3,000/mL. The highest dose is 1 mg/m2 After six monthly treatments, the treatment interval is reduced to every 2 to 3 months for the second 6 months. Further treatments are defined by the clinical course. Appropriate hydration and anti-emetics are indicated.

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