Topoisomerase Inhibitor

Etoposide

Approved 19 Sept 2001OralCapsule

The FDA lists this product in 15 strengths and forms.

Indications

Etoposide capsules are indicated in the management of the following neoplasms: Small Cell Lung Cancer Etoposide capsules in combination with other approved chemotherapeutic agents as first line treatment in patients with small cell lung cancer.

Contraindications

Etoposide capsules are contraindicated in patients who have demonstrated a previous hypersensitivity to etoposide or any component of the formulation.

Warnings and precautions

Patients being treated with etoposide must be frequently observed for myelosuppression both during and after therapy. Myelosuppression resulting in death has been reported. Dose-limiting bone marrow suppression is the most significant toxicity associated with etoposide therapy. Therefore, the following studies should be obtained at the start of therapy and prior to each subsequent cycle of etoposide: platelet count, hemoglobin, white blood cell count and differential.

The occurrence of a platelet count below 50,000/mm 3 or an absolute neutrophil count below 500/mm 3 is an indication to withhold further therapy until the blood counts have sufficiently recovered. Pregnancy Etoposide can cause fetal harm when administered to a pregnant woman. Etoposide has been shown to be teratogenic in mice and rats. In rats, an intravenous etoposide dose of 0.4 mg/kg/day (about 1/20 th 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 mg/kg/day and 3.6 mg/kg/day (about 1/7 th and 1/2 of human dose on a mg/m 2 basis) resulted in 90% and 100% embryonic resorptions.

In mice, a single 1.0 mg/kg (1/16 th of human dose on a mg/m 2 basis) dose of etoposide administered intraperitoneally on days 6, 7 or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations. An I.P. dose of 1.5 mg/kg (about 1/10 th of human dose on a mg/m 2 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.

Women of childbearing potential should be advised to avoid becoming pregnant. 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. Etoposide 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.

At a glance

Brand name: Etoposide
Pharmacologic class: Topoisomerase Inhibitor
Route: Oral
Dosage form: Capsule
Applicant: Mylan
Status: Prescription
FDA approval: 19 Sept 2001
Application: ANDA075635-001

Warnings and precautions

Adverse reactions

The following data on adverse reactions are based on both oral and intravenous administration of etoposide as a single agent, using several different dose schedules for treatment of a wide variety of malignancies. Hematologic Toxicity Myelosuppression is dose related and dose limiting, with granulocyte nadirs occurring 7 to 14 days after drug administration and platelet nadirs occurring 9 to 16 days after drug administration.

Bone marrow recovery is usually complete by day 20, and no cumulative toxicity has been reported. Fever and infection have also been reported in patients with neutropenia. Death associated with myelosuppression has been reported. The occurrence of acute leukemia with or without a preleukemic phase has been reported rarely in patients treated with etoposide in association with other antineoplastic agents (see WARNINGS ).

Gastrointestinal Toxicity Nausea and vomiting are the major gastrointestinal toxicities. The severity of such nausea and vomiting is generally mild to moderate with treatment discontinuation required in 1% of patients. Nausea and vomiting can usually be controlled with standard antiemetic therapy. Mild to severe mucositis/esophagitis may occur. Gastrointestinal toxicities are slightly more frequent after oral administration than after intravenous infusion.

Hypotension Transient hypotension following rapid intravenous administration has been reported in 1% to 2% of patients. It has not been associated with cardiac toxicity or electrocardiographic changes. No delayed hypotension has been noted. To prevent this rare occurrence, it is recommended that etoposide be administered by slow intravenous infusion over a 30- to 60-minute period. If hypotension occurs, it usually responds to cessation of the infusion and administration of fluids or other supportive therapy as appropriate.

When restarting the infusion, a slower administration rate should be used. Allergic Reactions Anaphylactic-like reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and/or hypotension have been reported to occur in 0.7% to 2% of patients receiving intravenous etoposide and in less than 1% of the patients treated with the oral capsules. These reactions have usually responded promptly to the cessation of the infusion and administration of pressor agents, corticosteroids, antihistamines or volume expanders as appropriate; however, the reactions can be fatal.

Hypertension and/or flushing have also been reported. Blood pressure usually normalizes within a few hours after cessation of the infusion. Anaphylactic-like reactions have occurred during the initial infusion of etoposide. Facial/tongue swelling, coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm, back pain and/or loss of consciousness have sometimes occurred in association with the above reactions. In addition, an apparent hypersensitivity-associated apnea has been reported rarely.

Rash, urticaria, and/or pruritus have infrequently been reported at recommended doses. At investigational doses, a generalized pruritic erythematous maculopapular rash, consistent with perivasculitis, has been reported. Alopecia Reversible alopecia, sometimes progressing to total baldness, was observed in up to 66% of patients. Other Toxicities The following adverse reactions have been infrequently reported: abdominal pain, aftertaste, constipation, dysphagia, asthenia, fatigue, malaise, somnolence, transient cortical blindness, optic neuritis, interstitial pneumonitis/pulmonary fibrosis, fever, seizure (occasionally associated with allergic reactions), Stevens-Johnson Syndrome, and toxic epidermal necrolysis, pigmentation, and a single report of radiation recall dermatitis.

Hepatic toxicity, generally in patients receiving higher doses of the drug than those recommended, has been reported with etoposide. Metabolic acidosis has also been reported in patients receiving higher doses. The incidences of adverse reactions in the table that follows are derived from multiple data bases from studies in 2,081 patients when etoposide was used either orally or by injection as a single agent. ADVERSE DRUG EFFECT PERCENT RANGE OF REPORTED INCIDENCE Hematologic toxicity Leukopenia (less than 1,000 WBC/mm 3 ) Leukopenia (less than 4,000 WBC/mm 3 ) Thrombocytopenia (less than 50,000 platelets/mm 3 ) Thrombocytopenia (less than 100,000 platelets/mm 3 ) Anemia 3 to 17 60 to 91 1 to 20 22 to 41 0 to 33 Gastrointestinal toxicity Nausea and vomiting Abdominal pain Anorexia Diarrhea Stomatitis Hepatic 31 to 43 0 to 2 10 to 13 1 to 13 1 to 6 0 to 3 Alopecia Peripheral neurotoxicity Hypotension Allergic reaction 8 to 66 1 to 2 1 to 2 1 to 2

Etoposide

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Etoposide

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information