No

Antineoplastic Agent, Irritant; Antineoplastic Agent, Podophyllotoxin Derivative; Vesicant

Treatment of refractory testicular tumors and small cell lung cancer

D

Hypersensitivity to etoposide, etoposide phosphate, or any component; I.T. administration is contraindicated

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Severe myelosuppression with resulting infection or bleeding may occur.

Refer to Etoposide monograph for details

Refer to Etoposide monograph for details

Refer to Etoposide monograph for details

Store intact vials of injection under refrigeration 2°C to 8°C (36°F to 46°F); protect from light

Reconstituted vials with 5 mL or 10 mL SWI, D₅W, NS, bacteriostatic SWI, or bacteriostatic NS to a concentration of 20 mg/mL or 10 mg/mL etoposide (22.7 mg/mL or 11.4 mg/mL etoposide phosphate), respectively. These solutions may be administered without further dilution or may be further diluted to a concentration as low as 0.1 mg/mL etoposide with either D₅W or NS. Solutions are stable in glass or plastic containers for at least 7 days at room temperature 20°C to 25°C (68°F to 77°F) or at least 31 days under refrigeration 2°C to 8°C (36°F to 47°F) for up to 24 hours.

Y-site incompatible with: Amphotericin B, cefepime hydrochloride, chlorpromazine hydrochloride, imipenem-cilastin sodium, methylprednisolone sodium phosphate, mitomycin, prochlorperazine edisylate

Y-site compatible with: Bleomycin, carboplatin, carmustine, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, floxuridine, fludarabine, fluorouracil, idarubicin, ifosfamide, methotrexate, mitoxantrone, paclitaxel, plicamycin, streptozocin, teniposide, thiotepa, vinblastine, vincristine, acyclovir, amikacin, ampicillin, ampicillin sodium-sulbactam sodium, aztreonam, cefazolin, cefoperazone, cefonicid, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, ciprofloxacin, clindamycin, doxycycline, fluconazole, ganciclovir, gentamicin, metronidazole, mezlocillin, minocycline, netilmicin, ofloxacin, piperacillin, piperacillin sodium-tazobactam, ticarcillin, ticarcillin disodium-clavulanate potassium, tobramycin, trimethoprim-sulfamethoxazole, vancomycin, zidovudine, aminophylline, bumetanide, buprenorphine, butorphanol, calcium gluconate, cimetidine, dexamethasone, diphenhydramine, dobutamine, dopamine, droperidol, enalaprilat, famotidine, furosemide, gallium nitrate, granisetron, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydroxyzine, leucovorin, lorazepam, magnesium sulfate, mannitol, meperidine, mesna, metoclopramide, morphine, nalbuphine, ondansetron, potassium chloride, promethazine, ranitidine, sodium bicarbonate

Etoposide phosphate is converted in vivo to the active moiety, etoposide, by dephosphorylation. Etoposide inhibits mitotic activity; inhibits cells from entering prophase; inhibits DNA synthesis. Initially thought to be mitotic inhibitors similar to podophyllotoxin, but actually have no effect on microtubule assembly. However, later shown to induce DNA strand breakage and inhibition of topoisomerase II (an enzyme which breaks and repairs DNA); etoposide acts in late S or early G2 phases.

Distribution: Average V_d: 3-36 L/m²; poor penetration across blood-brain barrier, with concentrations in the CSF being <10% that of plasma

Protein binding: 94% to 97%

Metabolism: In the liver (with a biphasic decay)

Half-life: Terminal: 4-15 hours; Children: 6-8 hours with normal renal and hepatic function

Elimination: Both unchanged drug and metabolites are excreted in the urine and a small amount (2% to 16%) excreted in feces; up to 55% of an I.V. dose is excreted unchanged in urine in children

Refer to individual protocols. Adults:

Testicular cancer: I.V. (in combination with other approved chemotherapeutic agents): Equivalent dose of etoposide phosphate to etoposide dosage range of 50-100 mg/m²/day on days 1-5 to 100 mg/m²/day on days 1, 3, and 5. Courses are repeated at 3- to 4-week intervals after adequate recovery from any toxicity.

Dosage adjustment in renal impairment:

Cl_cr 15-50 mL/minute: Administer 75% of normal dose

Cl_cr <15 mL minute: Data are not available and further dose reduction should be considered in these patients.

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

CAPD effects: Unknown

CAVH effects: Unknown

Dosage adjustment in hepatic impairment:

Bilirubin 1.5-3 mg/dL or AST 60-180 units: Reduce dose by 50%

Bilirubin 3-5 mg/dL or AST >180 units: Reduce by 75%

Bilirubin >5 mg/dL: Do not administer

CBC with differential, platelet count, and hemoglobin, vital signs (blood pressure), bilirubin, and renal function tests

No information available to require special precautions

No effects or complications reported

This drug can only be administered by infusion. During therapy, do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during therapy; frequent small meals may help. You may experience mild nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help). You may experience loss of hair (reversible); you will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). Yogurt or buttermilk may help reduce diarrhea. Frequent mouth care and use of a soft toothbrush or cotton swabs may help prevent mouth sores. This drug may cause sterility or birth defects. Report extreme fatigue, pain or numbness in extremities, severe GI upset or diarrhea, bleeding or bruising, fever, chills, sore throat, vaginal discharge, difficulty breathing, yellowing of eyes or skin, and any changes in color of urine or stool. Pregnancy/breast-feeding precautions: Do not get pregnant; use appropriate barrier contraceptive measures and avoid breast-feeding while on this drug and for several weeks after last dose. Do not breast-feed.

Powder for injection, lyophilized: 119.3 mg (100 mg base)

Budman DR, "Early Studies of Etoposide Phosphate, a Water-Soluble Prodrug," Semin Oncol, 1996, 23(6 Suppl 13):8-14.

Greco FA and Hainsworth JD, "Clinical Studies With Etoposide Phosphate," Semin Oncol, 1996, 23(6 Suppl 13):45-50.

Mummaneni V, Kaul S, Igwemezie LN, et al, "Bioequivalence Assessment of Etoposide Phosphate and Etoposide Using Pharmacodynamic and Traditional Pharmacokinetic Parameters," J Pharmacokinet Biopharm, 1996, 24(4):313-25.

Schacter LP, Igwemezie LN, Seyedsadr M, et al, "Clinical and Pharmacokinetic Overview of Parenteral Etoposide Phosphate," Cancer Chemother Pharmacol, 1994, 34(Suppl):S58-63.

Witterland AH, Koks CH, and Beijnen JH, "Etoposide Phosphate, the Water Soluble Prodrug of Etoposide," Pharm World Sci, 1996, 18(5):163-70.