Topoisomerase Inhibitor

Etoposide

Approved 14 Mar 1996InjectionInjectable

The FDA lists this product in 15 strengths and forms.

Indications

Etoposide Injection USP is indicated in the management of the following neoplasms: Refractory Testicular Tumors Etoposide Injection USP in combination therapy with other approved chemotherapeutic agents in patients with refractory testicular tumors who have already received appropriate surgical, chemotherapeutic, and radiotherapeutic therapy. Small Cell Lung Cancer Etoposide Injection USP in combination with other approved chemotherapeutic agents as first line treatment in patients with small cell lung cancer.

Contraindications

Etoposide Injection USP is 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 Injection USP 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 Injection USP therapy. Therefore, the following studies should be obtained at the start of therapy and prior to each subsequent cycle of etoposide Injection USP: 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. Physicians should be aware of the possible occurrence of an anaphylactic reaction manifested by chills, fever, tachycardia, bronchospasm, dyspnea, and hypotension. Higher rates of anaphylactic-like reactions have been reported in children who received infusions at concentrations higher than those recommended.

The role that concentration of infusion (or rate of infusion) plays in the development of anaphylactic-like reactions is uncertain. (See ADVERSE REACTIONS .) Treatment is symptomatic. The infusion should be terminated immediately, followed by the administration of pressor agents, corticosteroids, antihistamines, or volume expanders at the discretion of the physician. For parenteral administration, etoposide Injection USP should be given only by slow intravenous infusion (usually over a 30- to 60-minute period), since hypotension has been reported as a possible side effect of rapid intravenous injection.

Indications

Warnings and precautions

Adverse reactions

The following data on adverse reactions are based on intravenous administration of etoposide Injection USP 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 Injection USP 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 Injection USP be administered by slow intravenous infusion over a 30 to 60 minute period. If hypotension occurs, it usually responds to cessation of the infusion 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 Injection USP and in less than 1% of the patients treated with 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 Injection USP. 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 Injection USP. Metabolic acidosis has also been reported in patients receiving higher doses. Reports of extravasation with swelling have been received postmarketing. Rarely extravasation has been associated with necrosis and venous induration. The incidences of adverse reactions in the table that follows are derived from multiple databases 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 ) 3–17 Leukopenia (less than 4,000 WBC/mm 3 ) 60–91 Thrombocytopenia (less than 50,000 platelets/mm 3 ) 1–20 Thrombocytopenia (less than 100,000 platelets/mm 3 ) 22–41 Anemia 0–33 Gastrointestinal toxicity Nausea and vomiting 31–43 Abdominal pain 0–2 Anorexia 10–13 Diarrhea 1–13 Stomatitis 1–6 Hepatic 0–3 Alopecia 8–66 Peripheral neurotoxicity 1–2 Hypotension 1–2 Allergic reaction 1–2

Etoposide

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Etoposide

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

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