"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
Patients being treated with ETOPOPHOS (etoposide phosphate) must be frequently observed for myelosuppression both during and after therapy. Myelosuppression resulting in death has been reported following etoposide administration. Dose-limiting bone marrow suppression is the most significant toxicity associated with ETOPOPHOS (etoposide phosphate) therapy. Therefore, the following studies should be obtained at the start of therapy and prior to each subsequent cycle of ETOPOPHOS (etoposide phosphate) : platelet count, hemoglobin, white blood cell count, and 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 (etoposide phosphate) in patients with impaired renal or hepatic function has not been adequately evaluated. The toxicity profile of ETOPOPHOS (etoposide phosphate) 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 (etoposide phosphate) 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 (etoposide phosphate) 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 ½ 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 (etoposide phosphate) 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 (etoposide phosphate) have not been conducted in laboratory animals.
In all instances where the use of ETOPOPHOS (etoposide phosphate) is considered for chemotherapy, the physician must evaluate 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 should be taken according to the clinical judgement of the physician. Reinstitution of ETOPOPHOS (etoposide phosphate) therapy should be carried out with caution, and with adequate consideration of the further need for the drug and alertness as to possible recurrence of toxicity.
Patients with low serum albumin may be at an increased risk for etoposide associated toxicities.
Carcinogenesis (see WARNINGS), Mutagenesis, Impairment of Fertility
ETOPOPHOS (etoposide phosphate) was non-mutagenic in in vitro Ames microbial mutagenicity assay and the E. coli WP2 uvrA reverse mutation assay. Since ETOPOPHOS (etoposide phosphate) is rapidly and completely converted to etoposide in vivo and etoposide has been shown to be mutagenic in Ames assay, ETOPOPHOS (etoposide phosphate) should be considered as a potential mutagen in vivo.
In rats, an oral dose of ETOPOPHOS (etoposide phosphate) at 86.0 mg/kg/day (about 10 times the human dose on a mg/m² basis) or above administered for 5 consecutive days resulted in irreversible testicular atrophy. Irreversible testicular atrophy was also present in rats treated with ETOPOPHOS (etoposide phosphate) intravenously for 30 days at 5.11 mg/kg/day (about ½ of the human dose on a mg/m² basis).
Pregnancy Category D. (See WARNINGS.)
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ETOPOPHOS (etoposide phosphate) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established. Anaphylactic reactions have been reported in pediatric patients who received etoposide (see WARNINGS).
Clinical studies of etoposide for the treatment of refractory testicular tumors did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. Of more than 600 patients in four clinical studies in the NDA databases who received ETOPOPHOS (etoposide phosphate) or etoposide in combination with other chemotherapeutic agents for the treatment of small cell lung cancer, about one third were older than 65 years. When advanced age was determined to be a prognostic factor for response or survival in these studies, comparisons between treatment groups were performed for the elderly subset. In the one study (etoposide in combination with cyclophosphamide and vincristine compared with cyclophosphamide and vincristine or cyclophosphamide, vincristine, and doxorubicin) where age was a significant prognostic factor for survival, a survival benefit for elderly patients was observed for the etoposide regimen compared with the control regimens. No differences in myelosuppression were seen between elderly and younger patients in these studies except for an increased frequency of WHO Grade III or IV leukopenia among elderly patients in a study of etoposide phosphate or etoposide in combination with cisplatin. Elderly patients in this study also had more anorexia, mucositis, dehydration, somnolence, and elevated BUN levels than younger patients.
In five single-agent studies of etoposide phosphate in patients with a variety of tumor types, 34% of patients were aged 65 years or more. WHO Grade III or IV leukopenia, granulocytopenia, and asthenia were more frequent among elderly patients.
Postmarketing experience also suggests that elderly patients may be more sensitive to some of the known adverse effects of etoposide, including myelosuppression, gastrointestinal effects, infectious complications, and alopecia.
Although some minor differences in pharmacokinetic parameters between elderly and non-elderly patients have been observed, these differences were not considered clinically significant.
Etoposide and its metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to ETOPOPHOS (etoposide phosphate) may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS: Renal Impairment, for recommended dosing adjustments in patients with renal impairment).
Last reviewed on RxList: 5/12/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Etopophos Information
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