[.
]Action/Kinetics:
Mechanisms of action: alkylation by an activated carbonium ion, antimetabolite to inhibit DNA and RNA synthesis, and alkylation by combining with protein sulfhydryl groups. Is cell-cycle nonspecific. t1/2, biphasic, initial, 19 min; terminal, 5 hr. The t1/2 is increased to 55 min and 7.2 hr in those with renal and hepatic dysfunction. Probably localizes in liver. Limited amounts (14% of plasma level) enter CSF. Approximately 40% of drug excreted in urine unchanged within 6 hr. Secreted through the kidney tubules rather than filtered through the glomeruli.
Uses:
Metastatic malignant melanoma. Hodgkin's disease (with other agents). Investigational: In combination with cyclophosphamide and vincristine for malignant pheochromocytoma; in combination with tamoxifen for metastatic malignant melanoma.
Contraindications:
Lactation.
Special Concerns:
Dosage not established in children.
Additional Side Effects
Hematologic: Hemopoietic depression, especially leukopenia and thrombocytopenia which may cause death. GI: N&V; (more than 90% of clients within 1 hr after initial administration, which persists for 12-48 hr), anorexia, diarrhea. Dermatologic: Erythematous and urticarial rashes, photosensitivity reactions, alopecia, facial flushing, paresthesia. Miscellaneous: Flu-like syndrome, including fever, myalgia, and malaise. Hepatotoxicity, hypersensitivity, anaphylaxis.
Laboratory Test Alterations:
AST, ALT, and other enzymes.
Overdose Management:
Treatment: Monitor blood cell counts; supportive treatment.
How Supplied:
Injection: 10 mg/mL
Dosage
•IV Only
Malignant melanoma.
2-4.5 mg/kg/day for 10 days; may be repeated at 4-week intervals; or 250 mg/m2/day for 5 days; may be repeated at 3-week intervals.
Hodgkin's disease.
150 mg/m2/day for 5 days in combination with other drugs, and repeated q 4 weeks; or, 375 mg/m2 on day 1, with other drugs and repeated q 15 days.
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