Toposar (etoposide)

Dosage of etoposide must be based on the clinical and hematologic response and tolerance of the patient and whether or not other chemotherapy or radiation therapy has been or is also being used in order to obtain optimum therapeutic results with minimum adverse effects. Clinicians should consult published protocols for the dosage of etoposide and other chemotherapeutic agents and the method and sequence of administration. A repeat course of etoposide should not be administered until the patient's hematologic function is within acceptable limits. (See Cautions: Precautions and Contraindications.) When etoposide phosphate is used, dosage is expressed in terms of etoposide; 113.6 mg of etoposide phosphate is equivalent to 100 mg of etoposide.

The effects of renal or hepatic impairment on the elimination of etoposide have not been fully evaluated. Because a substantial fraction of the drug is excreted unchanged in urine, it is suggested that dosage reductions be considered in patients with impaired renal function. In patients with a measured creatinine clearance of greater than 50 mL/minute, no initial dose modification is required. In patients with a measured creatinine clearance of 15-50 mL/minute, 75% of the initial recommended etoposide dose should be administered. Although specific data are not available in patients with a measured creatinine clearance less than 15 mL/minute, further dose reduction should be considered. Subsequent etoposide dosing should be based on patient tolerance and clinical effect. Since etoposide-induced hematologic toxicity appeared to be more severe in patients with elevated serum bilirubin concentrations in one study and there is some evidence that total plasma clearance and elimination of the drug may be reduced in patients with impaired hepatic function, etoposide should probably be used with caution and the need for dosage reduction considered in patients with hepatic impairment.

Etoposide is administered orally and by slow IV infusion. Etoposide phosphate is administered by IV infusion.

Etoposide solutions should not be administered by rapid IV injection. (See Cautions: Cardiovascular Effects.) Because delayed, severe (sometimes fatal) toxicity has occurred in animals following intraperitoneal and intrapleural administration of etoposide, it is recommended that the drug not be administered by these routes.

The toxicity of rapidly infused etoposide phosphate in patients with impaired renal or hepatic function has not been adequately evaluated, and the toxicity profile of etoposide phosphate when infused at doses exceeding 175 mg/m2 has not been delineated.

To minimize the risk of hypotensive reactions, IV infusions of etoposide should be administered over a period of at least 30-60 minutes. The manufacturer states that a longer duration of administration may be used if the volume of fluid to be infused is a concern. Patients should be observed closely for possible hypotensive or anaphylactoid reactions during administration of the drug. (See Cautions: Precautions and Contraindications.) When a hypotensive reaction occurs and the infusion is discontinued and then restarted after appropriate treatment of the reaction, a slower rate of infusion should be employed. Etoposide has been administered by continuous IV infusion over 5 days, but this method of administration has not been shown to date to have any therapeutic advantage over intermittent IV infusions of the drug.

Etoposide phosphate solutions may be administered over 5-210 minutes.

The manufacturer recommends that protective gloves be used during handling of etoposide concentrate for injection and preparation of etoposide and etoposide phosphate solutions, since skin reactions associated with accidental exposure to the drug may occur. If etoposide concentrate for injection or a solution of the drug comes in contact with the skin, the affected area should be washed immediately and thoroughly with soap and water. If solutions of etoposide phosphate come in contact with the skin or mucosa, the affected skin should be washed immediately and thoroughly with soap and water, and the affected mucosa should be rinsed thoroughly with water.

Etoposide concentrate for injection must be diluted before administration. It is recommended that syringes with Luer-Lok(R) fittings be used for handling of etoposide concentrate for injection; when under pressure, needles have become displaced from etoposide-containing syringes without Luer-Lok(R) fittings, an effect which may be related to the drug's vehicle. The manufacturer recommends that the required dose of etoposide concentrate for injection be diluted to a final concentration of 0.2 or 0.4 mg/mL in 0.9% sodium chloride or 5% dextrose injection prior to slow IV infusion. (See Chemistry and Stability: Stability.) Etoposide concentrate for injection and the diluted solution for infusion should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Etoposide phosphate powder for injection should be reconstituted with 5 or 10 mL of sterile water for injection, 5% dextrose injection, 0.9% sodium chloride, bacteriostatic water for injection (with benzyl alcohol), or bacteriostatic sodium chloride for injection (with benzyl alcohol), resulting in a concentration equivalent to 20 or 10 mg of etoposide per mL (22.7 or 11.4 mg of etoposide phosphate per mL), respectively. Following reconstitution, the solution may be administered without further dilution, or it may be further diluted to concentrations as low as 0.1 mg of etoposide per mL with either 5% dextrose injection or 0.9% sodium chloride injection.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

No enhanced messaging available.

Etoposide may cause fetal harm when administered to pregnant women, but potential benefits from use of the drug may be acceptable in certain conditions despite possible risks to the fetus. Etoposide has been shown to be teratogenic and embryocidal in mice and rats at doses of 1-5% of the recommended human dose based on body surface area. In rats, etoposide caused dose-related maternal toxicity, embryotoxicity, and teratogenicity with IV dosages of 0.4-3.6 mg/kg daily. Embryonic resorptions, decreased fetal weights, and fetal abnormalities including major skeletal anomalies, exencephaly, encephalocele, and anophthalmia, were observed; even at an IV dosage of 0.13 mg/kg daily, a substantial increase in retarded ossification occurred. In mice, intraperitoneal etoposide doses of 1-2 mg/kg caused dose-related embryotoxicity, cranial abnormalities, and major skeletal malformations. There are no adequate and controlled studies to date using etoposide in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug. Etoposide should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. When the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.

It is not known whether etoposide is distributed into milk. Because of the potential for serious adverse reactions to etoposide in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced messaging available.