etoposide phosphate

Absorption: After IV administration, etoposide phosphate is rapidly converted to etoposide.

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
IV	unknown	12–19 days (granulocytes) 10–15 days (platelets)	21 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy and lactation;
Known intolerance to dextran.

Use Cautiously in:

OB: Patients with childbearing potential (may fertility in men and women);
Active infections;
↓bone marrow reserve;
Renal/hepatic impairment (dosage modification may be necessary);
Hypoalbuminemia;
Geri: May be at risk of adverse effects;
Pedi: Safety and effectiveness not established;
Other chronic debilitating illnesses.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, hypotension

Derm: alopecia, pruritis, rash, STEVENS-JOHNSON SYNDROME, urticaria

Endo: sterility

GI: anorexia, mucositis, nausea, vomiting, abdominal pain, constipation, diarrhea, taste alteration

Hemat: leukopenia, ANEMIA, THROMBOCYTOPENIA

Local: phlebitis at IV site

Neuro: malaise, dizziness

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.
Phenytoin, phenobarbital, carbamazepine, and valproic acid may ↓ levels
May ↑ risk of bleeding with warfarin.

Route/Dosage ⬆ ⬇

Testicular Neoplasms

Small-Cell Carcinoma of the Lung

Other regimens are used. Doses below are (and should always be) expressed as the desired etoposide dose).
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.
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 ⬆ ⬇

Powder for injection: 100 mg/vial (with dextran)

Assessment ⬆ ⬇

Monitor BP before and every 15 min during infusion. If hypotension occurs, stop infusion and notify 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 health care professional. 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 phosphate 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.
Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.

Lab Test Considerations:

Monitor CBC and differential before, prior to each cycle of therapy and periodically during therapy. The nadir of leukopenia occurs in 15–22, days, granulocytopenia in 12–19 days, and. and thrombocytopenia in 10–15 days after initiation of therapy. Bone marrow recovery usually occurs by day 21, but may be delayed. If absolute neutrophil count is <500/mm³ or platelet count is <50,000/mm³, hold therapy until blood counts have recovered sufficiently.
- 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 phosphate.
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.

IV Administration:

Intermittent Infusion: Reconstitute each vial with 5 or 10 mL of sterile water, D5W, or 0.9% NaCl for a concentration of 20 or 10 mg/mL, respectively.
- Diluent: May be administered undiluted or diluted with D5W or 0.9% NaCl.Concentration: as low as 0.1 mg/mL.
- Reconstituted solutions are stable for 24 hr at room temperature or for 7 days if refrigerated.
Rate: Administer over 5–210 min. Do not administer as a bolus injection.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of etoposide phosphate to patient.
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.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: Advise patient to use contraception. May result in oligospermia, azoospermia, and permanent loss of fertility in male patients. May damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Males with female sexual partners of reproductive potential should use condoms during therapy and for at least 4 mo after final dose. May cause infertility, premature menopause, and amenorrhea in female patients. Recovery of menses and ovulation is related to age at treatment. Advise females of reproductive potential to use effective contraception during therapy and for at least 6 mo after final dose.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇