etoposide

High Alert

Refractory testicular neoplasms (IV only) (used in combination with other chemotherapeutic agents in patients who have already received chemotherapy, surgery, or radiation).
Small cell lung carcinoma (PO and IV) (first-line therapy; used in combination with other chemotherapeutic agents).

Unlabeled Use:

Lymphomas and some leukemias.Uterine cancer.Brain tumors.

Action ⬆ ⬇

Damages DNA before mitosis (cycle-dependent and phase-specific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics ⬆ ⬇

Absorption: Variably absorbed after oral administration (bioavailability ~50%). IV administration results in complete bioavailability.

Distribution: Rapidly distributed; poorly enters the CSF; probably crosses placenta; enters breast milk.

Protein Binding: 97%.

Metabolism/Excretion: Some metabolism by the liver with biliary excretion, 44% excreted in feces; 45% excreted unchanged by the kidneys.

Half-Life: 4–11 hr.

Time/Action Profile ⬆ ⬇

(noted as effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	7–14 days (granulocytes) 9–16 days (platelets)	20 days
IV	unknown	7–14 days (granulocytes) 9–16 days (platelets)	20 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Pregnancy;
Lactation;
Known intolerance to ethyl alcohol or polysorbate 80 (IV only).

Use Cautiously in:

Patients with childbearing potential;
Active infections;
Decreased bone marrow reserve;
Renal/hepatic impairment (dose modification may be necessary);
Hypoalbuminemia;
Elderly (may be at increased risk of adverse effects);
Children (safety and effectiveness not established);
Other chronic debilitating illnesses.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension(IV)

Derm: alopecia, pruritis, rash, urticaria

Endo: sterility

GI: anorexia, diarrhea, nausea, vomiting, abdominal pain, stomatitis

Hemat: anemia, leukopenia, thrombocytopenia

Local: phlebitis at IV site

Neuro: drowsiness, fatigue, peripheral neuropathy

Misc: ANAPHYLAXISALLERGIC REACTIONS INCLUDING, fever

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
May alter immune response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage ⬆ ⬇

Testicular Neoplasms

Small-Cell Carcinoma of the Lung

Other regimens are used
IV (Adults ): Dose ranges from 50–100 mg/m² daily for 5 days up to 100 mg/m² daily on days 1, 3, and 5; repeat at 3–4 wk intervals.
PO (Adults ): Dose ranges from 70 mg/m² daily for 4 days up to 100 mg/m² daily for 5 days (round dose to the nearest 50 mg); repeat at 3–4 wk intervals.
IV (Adults ): Dose ranges from 35 mg/m² daily for 4 days up to 50 mg/m² daily for 5 days; repeat at 3–4 wk intervals.

Availability ⬆ ⬇

(Generic available)

Capsules: 50 mg
Injection: 20 mg/mL

Assessment ⬆ ⬇

Monitor BP before and every 15 min during infusion. If hypotension occurs, stop infusion and notify physician or other health care professional. After stabilizing BP with IV fluids and supportive measures, infusion may be resumed at slower rate.
Monitor for hypersensitivity reaction (fever, chills, dyspnea, pruritus, urticaria, bronchospasm, tachycardia, hypotension). If these occur, stop infusion and notify physician. Keep epinephrine, an antihistamine, corticosteroids, volume expanders, and resuscitative equipment close by in the event of an anaphylactic reaction.
Assess for signs of infection (fever, chills, cough, hoarseness, lower back or side pain, sore throat, difficult or painful urination). Notify health care professional if these symptoms occur.
Assess for bleeding (bleeding gums, bruising, petechiae, guaiac test stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min.
Monitor intake and output, appetite, and nutritional intake. Etoposide causes mild-to-moderate nausea and vomiting. Prophylactic antiemetics may decrease frequency and duration of nausea and vomiting.
Adjust diet as tolerated to help maintain fluid and electrolyte balance and nutritional status.

Lab Test Considerations:

Monitor CBC and differential before and periodically during therapy. The nadir of leukopenia occurs in 7–14 days. Notify health care professional if absolute neutrophil count is <1000/mm³. The nadir of thrombocytopenia occurs in 9–16 days. Notify health care professional if the platelet count is <75,000/mm³. Recovery of leukopenia and thrombocytopenia occurs in 20 days.
- Monitor liver function studies (AST, ALT, LDH, bilirubin) and renal function studies (BUN, creatinine) before and periodically during therapy to detect hepatotoxicity and nephrotoxicity.

Implementation ⬆ ⬇

Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings. .
Do not confuse etoposide with etoposide phoshpate.
Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
- Avoid contact with skin. Use Luer-Lok tubing to prevent accidental leakage. If contact with skin occurs, immediately wash skin with soap and water.
PO: Capsules should be refrigerated. Capsules are stable for 24 mo when refrigerated.

IV Administration:

Intermittent Infusion: Diluent: Dilute 5 mL vial with D5W or 0.9% NaCl.Concentration: 200–400 mcg/mL The 200 mcg/mL solution is stable for 96 hr. The 400 mcg/mL solution is stable for 48 hr. Concentrations >400 mcg/mL are not recommended, because crystallization is likely. Discard solution if crystals are present.
Rate: Infuse slowly over 30–60 min. Temporary hypotension may occur with infusion rates shorter than 30 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take etoposide as directed, even if nausea or vomiting occurs. If vomiting occurs shortly after dose is taken, consult health care professional. If a dose is missed, do not take at all.
Advise patient to notify health care professional if fever; chills; sore throat or other signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
Instruct patient to notify health care professional if rapid heartbeat, difficulty breathing, abdominal pain, yellow skin/eyes, weakness, paresthesia, or gait disturbances occur.
Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Viscous lidocaine swishes may be used if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
Discuss with patient the possibility of hair loss. Explore coping strategies.
Advise patient to use contraception.
Instruct patient not to receive any vaccinations without advice of health care professional.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇