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Action/Kinetics:
Antibiotic produced by
Streptomyces caespitosus that inhibits DNA synthesis. At high doses both RNA and protein synthesis are inhibited. Most active during late G
1 and early S stages.
t
1/2, initial: 5-15 min;
final: 50 min. Metabolized in liver; 10% excreted unchanged in urine, more when dose is increased.
Uses:
Palliative treatment and adjunct to surgical or radiologic treatment of disseminated adenocarcinoma of the stomach and pancreas. Used in combination with other agents (not recommended as a single agent for primary treatment or in place of surgery and/or radiotherapy).
Investigational: Superficial bladder cancer; cancer of the breast, head and neck, lung, cervix; colorectal cancer; biliary cancer; chronic myelocytic leukemia. Ophthalmic solution used as an adjunct to surgical excision to treat primary or recurrent pterygia.
Contraindications:
Pregnancy and lactation. Thrombocytopenia, coagulation disorders, increase in bleeding tendency due to other causes. In clients with a serum creatinine level greater than 1.7 mg/dL.
Special Concerns:
Use with extreme caution in presence of impaired renal function.
Additional Side Effects
Severe bone marrow depression, especially leukopenia and thrombocytopenia. Pulmonary toxicity including dyspnea with nonproductive cough.
Microangiopathic hemolytic anemia with renal failure and hypertension (hemolytic uremic syndrome) especially when used long-term in combination with fluorouracil. Cellulitis. Extravasation causes severe necrosis of surrounding tissue.
Respiratory distress syndrome in adults, especially when used with other chemotherapy.
Drug Interactions:
Severe bronchospasm and SOB when used with vinca alkaloids.
How Supplied:
Powder for injection: 5 mg, 20 mg, 40 mg
Dosage
?IV Only
10-20 mg/m
2 as a single dose via infusion q 6-8 wk. Subsequent courses of treatment are based on hematologic response; do not repeat until leukocyte count is at least 4,000/mm
3 and platelet count is at least 100,000/mm
3.