Class: Podophyllotoxin derivative
- Injection, lyophilized powder for solution 100 mg vial
- Capsules 50 mg
- Injection, solution, concentrate 20 mg/mL
Etoposide's main effect appears to be at the G 2 portion of the cell cycle. At high concentrations (10 mcg/mL or more), lysis of cells entering mitosis is seen; at low concentrations (0.3 to 10 mcg/mL), cells are inhibited from entering prophase. Predominant macromolecular effect appears to be DNA synthesis inhibition.
Bioavailability is approximately 50% (oral).
Distribution half-life is approximately 1.5 h. Vd is approximately 18 to 29 L (at steady state). 97% is protein bound.
Etoposide phosphate is rapidly dephosphonylated to etoposide in the plasma. Etoposide is extensively metabolized in the liver (including CYP3A4).
The half-life is approximately 4 to 11 h. Cl is 33 to 48 mL/min. 42% to 67% is excreted in the urine, and 0% to 16% is excreted in the feces. Less than 50% is excreted in the urine, and less than 6% is excreted in bile as etoposide.
Special PopulationsRenal Function Impairment
Total body Cl is reduced, AUC is increased, and Vd is lower.
Indications and Usage
In combination with other chemotherapeutic agents in patients with small cell lung cancer.Etopophos , Toposar
In combination with other chemotherapeutic agents in patients with refractory testicular tumors.
Bladder carcinoma, lymphomas, leukemias, Ewing sarcoma, Kaposi sarcoma, brain tumors, gestational trophoblastic tumors, ovarian germ cell tumors, rhabdomyosarcomas, Wilms tumor, bone marrow transplantation.
Dosage and AdministrationSmall Cell Lung Cancer
IV Dosage ranges from 35 mg/m 2 /day for 4 days to 50 mg/m 2 /day for 5 days. Repeat chemotherapy courses at 3- to 4-week intervals after adequate recovery from any toxicity. PO Two times the IV dose rounded to the nearest 50 mg.Testicular Cancer
IV Dosage ranges from 50 to 100 mg/m 2 /day on days 1 through 5 to 100 mg/m 2 /day on days 1, 3, and 5. Repeat chemotherapy courses at 3- to 4-week intervals after adequate recovery from any toxicity.Adjustment in Renal Insufficiency
For patients with CrCl of 15 to 50 mL/min, give 75% of the usual dose. Consider further dose reduction for those with CrCl less than 15 mL/min.
- Modify dose to take into account the myelosuppressive effects of other drugs in the combination or the effects of prior x-ray therapy or chemotherapy that may have compromised bone marrow reserve.
- Etoposide solution for injection can be mixed to a final concentration 0.4 mg/mL or less with orange juice, apple juice, or lemonade for oral administration.
- Stable for 3 h at room temperature.
- Dilute prior to use with dextrose 5% or sodium chloride 0.9% to final concentration of 0.2 or 0.4 mg/mL. Concentrations less than 0.4 mg/mL may precipitate.
- Infuse over 30 to 60 min. Do not give by rapid IV injection because of the risk of hypotension.
Refrigerate; can be stored at room temperature for 3 mo.Etopophos
Store unopened vials refrigerated at 36° to 46°F. Protect from light. Reconstituted solutions can be stored in glass or plastic containers refrigerated at 36° to 46°F for 7 days; following reconstitution with sterile water for injection, dextrose 5% injection, or sodium chloride 0.9%, store at 68° to 77°F for 24 hours; or following reconstitution with bacteriostatic water for injection with benzyl alcohol or bacteriostatic sodium chloride for injection with benzyl alcohol, store at 68° to 77°F for 48 hours.Etoposide capsules
Store refrigerated at 36° to 46°F. Do not freeze.Toposar
Store at 59° to 86°F. Do not freeze. Vials diluted as recommended to 0.2 mg/mL or 0.4 mg/mL may be stored at 77°F for 96 hours and 24 hours, respectively.
Drug InteractionsAzole antifungal agents (eg, ketoconazole)
Etoposide plasma concentrations may be elevated, increasing the risk of adverse reactions.Cyclosporine
High-dose cyclosporine has increased etoposide exposure 89% and decreased Cl 38%. The risk of etoposide toxicity may be increased.Grapefruit juice
Etoposide plasma concentrations may be reduced, decreasing the pharmacologic effect.Warfarin
Etoposide may increase the hypoprothrombinemic effects of warfarin.
Laboratory Test Interactions
None well documented.
Peripheral neurotoxicity (2%).
Nausea and vomiting (43%); anorexia, diarrhea (13%); stomatitis (6%); abdominal pain (2%).
Leukopenia (less than 1,000 WBC/mm 3 [17%], less than 4,000 WBC/mm 3 [91%]); thrombocytopenia (less than 50,000 platelets/mm 3 [20%], less than 1,000,000 platelets/mm 3 [41%]); anemia (33%).
Hepatic toxicity (3%).
Allergic reactions, including anaphylactic-type reactions (2%).
Severe cases with resulting infection or bleeding may occur. Dose-limiting bone marrow suppression is the most significant toxicity.
Frequently monitor for myelosuppression during and after therapy. Perform periodic CBCs prior to therapy, during the course of therapy, and after therapy. At lease 1 CBC determination should be done prior to each dose of etoposide.BP
Monitor BP before and after infusion.
Category D .
Safety and efficacy in children not established.
Use with caution because elderly patients are more likely to have decreased renal function. Postmarketing experience suggests that elderly patients may be more sensitive to some etoposide adverse reactions, including alopecia, GI effects, infections, myelosuppression.
Dosage adjustments may be needed.
Patients with low serum albumin may be at increased risk of etoposide toxicity.
Anaphylaxis manifested by chills, fever, tachycardia, bronchospasm, dyspnea, facial flushing, hypertension, or hypotension may occur.
Administer by slow IV infusion because hypotension may occur with rapid IV injection.
Can cause local irritation or phlebitis. Refer to your institution-specific protocol.
Bone marrow suppression.
- Contraceptive measures are recommended during treatment.
- Notify health care provider of any of the following: chills, difficult breathing, fever, rapid heartbeat.
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