etoposide
Toposar, VePesid

Available forms
Available by prescription only
Capsules: 50 mg
Injection: 20-mg/ml multiple-dose vials

Indications and dosages
Dosage and indications may vary. Check literature for current protocol.
 Small-cell carcinoma of the lung. Adults: 70 mg/m² P.O. daily (rounded to the nearest 50 mg) for 4 days. Or, 100 mg/m² P.O. (rounded to the nearest 50 mg) daily for 5 days. Repeat q 3 to 4 weeks. Or, 35 mg/m² I.V. daily for 4 days or 50 mg/m² I.V. daily for 5 days. Repeat q 3 to 4 weeks.
 Testicular carcinoma. Adults: 50 to 100 mg/m² I.V. daily on days 1 to 5. Or, 100 g/m² daily on days 1, 3, and 5 of a regimen repeated q 3 or 4 weeks.
 AIDS-related Kaposi’s sarcoma ◇. Adults: 150 mg/m² daily I.V. for 3 consecutive days every 4 weeks. Repeat cycles as needed.
≡ Dosage adjustment. Patients with impaired renal function may need dosage adjustment.

Pharmacodynamics
Antineoplastic action: Etoposide exerts cytotoxic action by arresting cells in the metaphase portion of cell division. Drug also inhibits cells from entering mitosis and depresses DNA and RNA synthesis at the G2 portion of the cell cycle.

Pharmacokinetics
Absorption: Only moderately absorbed across the GI tract after oral administration. Etoposide’s bioavailability ranges from 25% to 75%, with an average of 50% of the dose being absorbed.
Distribution: Distributed widely into body tissues; the highest levels are found in the liver, spleen, kidneys, healthy brain tissue, and brain tumor tissue. It crosses the blood-brain barrier to a limited and variable extent. Etoposide is about 94% bound to serum albumin.
Metabolism: Only a small portion of a dose of etoposide is metabolized. Metabolism occurs in the liver.
Excretion: Excreted primarily in the urine as unchanged drug. A smaller portion of a dose is excreted in the feces. The plasma elimination of etoposide is described as biphasic, with an initial phase half-life of about 1/2 to 2 hours and a terminal phase of about 5 1/4 to 11 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to etoposide, teniposide, or Cremaphor EL. Use cautiously in patients who have had cytotoxic or radiation therapy.

Interactions
Drug-drug. Cisplatin: Increases cytotoxicity of cisplatin against certain tumors. May be used for this purpose.
Warfarin: May cause elongation of PT and INR. Monitor patient closely.

Adverse reactions
CNS: peripheral neuropathy.
CV: hypotension (from too-rapid infusion).
GI: nausea and vomiting, anorexia, diarrhea, abdominal pain, stomatitis.
Hematologic: anemia, myelosuppression, LEUKOPENIA, THROMBOCYTOPENIA. 
Skin: reversible alopecia.
Other: anaphylaxis.

Effects on lab test results
• May decrease hemoglobin and platelet, WBC, RBC, and neutrophil counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, nausea, and vomiting.
 Treatment is usually supportive and includes transfusion of blood components, antiemetics, and appropriate symptomatic therapy.

Special considerations
• Pretreatment with antiemetics may reduce frequency and duration of nausea and vomiting.
• At doses below 200 mg, extent of absorption after oral administration isn’t affected by food.
• Have diphenhydramine, hydrocortisone, epinephrine, and airway available in case of an anaphylactoid reaction.
• Etoposide has produced complete remissions in small-cell lung cancer and testicular cancer.
 ALERT Using gloves is recommended when handling etoposide. If solution contacts skin or mucosa, immediately wash the area with soap and water.
• For I.V. administration, dilute etoposide in either D₅W or normal saline solution to 0.2 or 0.4 mg/ml. Higher concentrations may crystallize. Give etoposide by slow I.V. infusion (over at least 30 minutes) to prevent severe hypotension.
• Monitor blood pressure before and at 30-minute intervals during infusion. If systolic blood pressure goes below 90 mm Hg, stop infusion.
• Monitor CBC. Drug shouldn’t be given if platelet count is less than 50,000/mm³ or absolute neutrophil count is less than 500/mm³.
• GI toxicity occurs more frequently after oral administration.
Pregnant patients
• Risk of fetal harm is high. During pregnancy, use drug only for life-threatening conditions or severe disease when much safer drugs aren’t available or are ineffective.
Breast-feeding patients
• Drug appears in breast milk. Its use in breast-feeding women isn’t recommended.
Pediatric patients
• Safety and effectiveness in children haven’t been established.
Geriatric patients
• Elderly patients may be particularly susceptible to the hypotensive effects of etoposide.

Patient education
• Advise patient about potential adverse reactions, and instruct patient to immediately report vomiting that occurs shortly after a dose.
• Advise patient to report sore throat, fever, or unusual bruising or bleeding.
• Advise patient to avoid exposure to people with infections.
• Tell patient not to receive immunizations during therapy with etoposide. Tell other family members to avoid immunizations during this time as well.
• Advise patient to use contraceptive measures during therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use