ould be taken according to the clinical judgement of the physician. Reinstitution of Etopophos 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.
Drug Interactions
Caution should be exercised when administering Etopophos with drugs that are known to inhibit phosphatase activities (e.g., levamisole hydrochloride). High-dose cyclosporin A resulting in concentrations above 2000 ng/mL administered with oral etoposide has led to an 80% increase in etoposide exposure with a 38% decrease in total body clearance of etoposide compared to etoposide alone.
Laboratory Tests
Periodic complete blood counts should be done during the course of Etopophos treatment. They should be performed prior to each cycle of therapy and at appropriate intervals during and after therapy.
Renal Impairment
In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance:
Measured
Creatinine Clearance
>50 mL/min
15-50 mL/min
etoposide 100% of dose 75% of dose
Subsequent etoposide dosing should be based on patient tolerance and clinical effect. Equivalent dose adjustments of Etopophos should be used.
Data are not available in patients with creatinine clearances <15 mL/min and further dose reduction should be considered in these patients.
Carcinogenesis (see WARNINGS), Mutagenesis, Impairment of Fertility
Etopophos was non-mutagenic in in vitro Ames microbial mutagenicity assay and the E. coli WP2 uvrA reverse mutation assay. Since Etopophos is rapidly and completely converted to etoposide in vivo and etoposide has been shown to be mutagenic in Ames assay, Etopophos should be considered as a potential mutagen in vivo.
In rats, an oral dose of Etopophos 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 intravenously for 30 days at 5.11 mg/kg/day (about 1/2 of the human dose on a mg/m2 basis).
Pregnancy
Pregnancy Category D. (See WARNINGS.)
Nursing Mothers
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, 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.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Anaphylactic reactions have been reported in pediatric patients who received etoposide (see WARNINGS).
Geriatric Use
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 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 |
