differential. The occurrence of a platelet count below 50,000/mm3 or an absolute neutrophil count below 500/mm3 is an indication to withhold further therapy until the blood counts have sufficiently recovered. The toxicity of rapidly infused Etopophos in patients with impaired renal or hepatic function has not been adequately eva luated. The toxicity profile of Etopophos when infused at doses >175 mg/m2 has not been delineated.
Physicians should be aware of the possible occurrence of an anaphylactic reaction manifested by chills, fever, tachycardia, bronchospasm, dyspnea, and hypotension. Higher rates of anaphylactic-like reactions have been reported in children who received infusions of etoposide at concentrations higher than those recommended. The role that concentration of infusion (or rate of infusion) plays in the development of anaphylactic-like reactions is uncertain. (See ADVERSE REACTIONS.) Treatment is symptomatic. The infusion should be terminated immediately, followed by the administration of pressor agents, corticosteroids, antihistamines, or volume expanders at the discretion of the physician.
Injection site reactions may occur during the administration of Etopophos (see ADVERSE REACTIONS). Closely monitor the infusion site for possible infiltration during drug administration. No specific treatment for extravasation reactions is known.
Etopophos can cause fetal harm when administered to a pregnant woman. Etoposide has been shown to be teratogenic in mice and rats, and it is therefore likely that Etopophos is also teratogenic.
In rats, an intravenous etoposide dose of 0.4 mg/kg/day (about 1/20 of the human dose on a mg/m2 basis) during organogenesis caused maternal toxicity, embryotoxicity, and teratogenicity (skeletal abnormalities, exencephaly, encephalocele, and anophthalmia); higher doses of 1.2 and 3.6 mg/kg/day (about 1/7 and 1/2 of the human dose on a mg/m2 basis) resulted in 90% and 100% embryonic resorptions. In mice, a single 1.0 mg/kg (1/16 of the human dose on a mg/m2 basis) dose of etoposide administered intraperitoneally on days 6, 7, or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations. An intraperitoneal dose of 1.5 mg/kg (about 1/10 of the human dose on a mg/m2 basis) on day 7 of gestation caused an increase in the incidence of intrauterine death and fetal malformations and a significant decrease in the average fetal body weight.
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be warned of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Etopophos should be considered a potential carcinogen in humans. The occurrence of acute leukemia with or without a preleukemic phase has been reported in rare instances in patients treated with etoposide alone or in association with other neoplastic agents. The risk of development of a preleukemic or leukemic syndrome is unclear. Carcinogenicity tests with Etopophos have not been conducted in laboratory animals.
Precautions
General
In all instances where the use of Etopophos is considered for chemotherapy, the physician must eva luate the need and usefulness of the drug against the risk of adverse reactions. Most such adverse reactions are reversible if detected early. If severe reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures sh |
