ETOPOSIDE

ETOPOSIDE
(e-toe-po'side)
Etopophos, VePesid
Classifications: antineoplastic; mitotic inhibitor;
Therapeutic: antineoplastic, cell-cycle specific

Prototype: Vincristine
Pregnancy Category: D

Availability

50 mg capsules; 20 mg/mL injection; 100 mg lyophilized powder for injection

Action

Semisynthetic derivative of May apple plant. Produces cytotoxic action by arresting G2 (resting or premitotic) phase of cell cycle; also acts on S phase of DNA synthesis. High doses cause lysis of cells entering mitotic phase, and lower doses inhibit cells from entering prophase.

Therapeutic Effect

Antineoplastic effect is due to its ability to arrest mitosis (cell division).

Uses

Treatment of refractory testicular neoplasms, in patients who have already received appropriate surgical, chemotherapeutic, and radiation therapy; for treatment of choriocarcinoma in women and small cell carcinoma of the lung.

Unlabeled Uses

Hodgkin's and non-Hodgkin's lymphomas, acute myelogenous (nonlymphocytic) leukemia.

Contraindications

Severe bone marrow depression; severe hepatic or renal impairment; existing or recent viral infection, bacterial infection; intraperitoneal, intrapleural, or intrathecal administration; pregnancy (category D), lactation. Safe use in children is not established.

Cautious Use

Impaired kidney or liver function; gout; radiation therapy.

Route & Dosage

Testicular Carcinoma
Adult: IV 100 mg/m2/d for 5 consecutive days or 100 mg/m2 on days 1, 3, and 5 q3–4wk for 3–4 courses PO Twice the IV dose rounded to the nearest 50 mg

Small Cell Lung Carcinoma
Adult: IV 35 mg/m2/d for 4 consecutive days to 50 mg/m2/d for 5 consecutive days q3–4wk PO Twice the IV dose rounded to the nearest 50 mg

Hepatic Impairment
Total bilirubin 1.5–3 mg/dL: decrease by 50%, 3.1–5 mg/dL: decrease by 75%, over 5 mg/dL hold dose

Renal Impairment
Clcr 45–60 mL/min: reduce dose 15%; 30–44 mL/min: reduce dose 20%; <30 mL/min: reduce dose 25%

Administration

Oral
  • Oral dose is usually in the range of 70–100 mg/m2 daily, rounded to nearest 50 mg.
  • Refrigerate capsules at 2°–8° C (36°–46° F) unless otherwise directed. Do not freeze.
Intravenous
  • Note: Wear disposable surgical gloves when preparing or disposing of etoposide. Wash immediately with soap and water if skin comes in contact with drug.

PREPARE: IV Infusion: Etoposide concentration for injection: Each 100 mg must be diluted with 250–500 mL of D5W or NS to produce final concentrations of 0.2–0.4 mg/mL. Etoposide phosphate: Add 5 or 10 mL of sterile water for injection, D5W, NS, bacteriostatic water for injection, or bacteriostatic NS for injection to yield 20 or 10 mg/mL etoposide, respectively. May be given as prepared or further diluted to as low as 0.1 mg/mL in either D5W or NS.  

ADMINISTER: IV Infusion: Give by slow IV infusion over 30–60 min to reduce risk of hypotension and bronchospasm. Before administration, inspect solution for particulate matter and discoloration. Solution should be clear and yellow. If crystals are present, discard.  

INCOMPATIBILITIES Y-site: Cefepime, filgrastim, gallium, idarubicin.

  • Diluted solutions with concentration of 0.2 mg/mL are stable for 96 h, and the 0.4 mg/mL solutions are stable for 48 h under normal room fluorescent light in glass or plastic (PVC) containers.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (sweating, chills, fever, coryza, tachycardia; throat, back and general body pain; abdominal cramps, flushing, substernal chest pain, dyspnea, bronchospasm, pulmonary edema, anaphylactoid reaction). CNS: Peripheral neuropathy, paresthesias, weakness, somnolence, unusual tiredness, transient confusion. CV: Transient hypotension; thrombophlebitis with extravasation. GI: Nausea, vomiting, dyspepsia, anorexia, diarrhea, constipation, stomatitis. Hematologic: Leukopenia (principally granulocytopenia), thrombocytopenia, severe myelosuppression, anemia, pancytopenia, neutropenia. Respiratory: Pleural effusion, bronchospasm. Skin: Reversible alopecia (can progress to total baldness); radiation recall dermatitis; necrosis, pain at IV site.

Interactions

Drug: anticoagulants, antiplatelet agents, nsaids, aspirin may increase risk of bleeding. Avoid concurrent use of live vaccines.

Pharmacokinetics

Absorption: Approximately 50% from GI tract. Peak: 1–1.5 h. Distribution: Variable penetration into CSF. Metabolism: In liver. Elimination: 44–60% in urine, 2–16% in feces over 3 d. Half-Life: 5–10 h.

Nursing Implications

Assessment & Drug Effects

  • Check IV site during and after infusion. Extravasation can cause thrombophlebitis and necrosis.
  • Be prepared to treat an anaphylactoid reaction (see Appendix F). Stop infusion immediately if the reaction occurs.
  • Monitor vital signs during and after infusion. Stop infusion immediately if hypotension occurs.
  • Lab tests: Perform baseline all prior to and at regular intervals during therapy, and before each subsequent treatment course. Tests include: CBC with differential; liver and kidney function tests (AST, ALT, serum bilirubin, LDH, BUN, serum creatinine).
  • Withhold therapy when an absolute neutrophil count is below 500/mm3 or a platelet count below 50,000/mm3.
  • Be alert to evidence of patient complaints that might suggest development of leukopenia (see Appendix F), infection (immunosuppression), and bleeding.
  • Protect patient from any trauma that might precipitate bleeding during period of platelet nadir particularly. Withhold invasive procedures if possible.

Patient & Family Education

  • Learn possible adverse effects of etoposide, such as blood dyscrasias, alopecia, carcinogenesis, before treatment begins.
  • Make position changes slowly, particularly from lying to upright position because transient hypotension after therapy is possible.
  • Inspect mouth daily for ulcerations and bleeding. Avoid obvious irritants such as hot or spicy foods, smoking, alcohol.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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