etoposide (Rx)

>10%

Leukopenia (60-91%)

Nausea and Vomiting (30-40%)

Thrombocytopenia (28-41%)

Alopecia (20-90%)

Anorexia (13%)

Diarrhea (13%)

Leukopenia (60-91%)

Anemia (≤33%)

1-10%

Pancytopenia (7%)

Stomatitis (6%)

Hepatic toxicity (3%)

Type 1 hypersensitivity (2%)

Orthostatic hypotension (1-2%)

Peripheral neuropathy (1-2%)

Frequency Not Defined

Malaise

Shivering

Asthenia

Fever

Mucous membrane inflammation

Hyperuricemia

Local soft tissue toxicity has been reported following extravasation; see section on IV information for extravasation management

Contraindications

Hypersensitivity to etoposide or teniposide

Cautions

Withhold further treatment if platelet <50,000/mm³ or ANC <500/mm³

Use caution in hepatic impairment

Do NOT inject rapidly (may cause hypotension); infuse over at least 30-60 min

Injection site reactions may occur during administration; monitor closely

Avoid pregnancy

May result in oligospermia, azoospermia, and permanent loss of fertility; sperm counts have been reported to return to normal levels in some men, and in some cases has occurred several years after end of therapy; 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 months after final dose

May cause infertility in females of reproductive potential and result in amenorrhea; premature menopause can occur; recovery of menses and ovulation is related to age at treatment; advise females of reproductive potential to use effective contraception during treatment for at least 6 months after final dose

Occurrence of acute leukemia with or without a preleukemic phase reported in rare instances in patients treated with etoposide alone or in association with other neoplastic agents; risk of development of preleukemic or leukemic syndrome unclear

Prescriber must consider benefits versus risk of therapy; if severe reactions occur, dose should be reduced or discontinued and appropriate corrective measures taken; reinstitution of therapy should be carried out with caution, and with adequate consideration of further need for drug and alertness as to possible recurrence of toxicity

Patients with low serum albumin may be at increased risk for etoposide associated toxicities

Anaphylactic reaction manifested by chills, fever, tachycardia, bronchospasm, dyspnea, and hypotension reported; higher rates of anaphylactic-like reactions reported in children who received infusions of etoposide at concentrations higher than those recommended; the role that concentration of infusion (or rate of infusion) plays in development of anaphylactic-like reactions is uncertain; treatment is symptomatic; infusion should be terminated immediately, followed by administration of pressor agents, corticosteroids, antihistamines, or volume expanders at the discretion of the physician

Reversible cases of acute renal failure reported with administration of high dose (2220 mg/m²) with total body irradiation used for hematopoietic stem cell transplantation; the formulation contains dextran 40, which has been associated with acute renal failure when administered in high doses

Pregnancy: Based on animal data and its mechanism of action, etoposide can cause fetal harm when administered to a pregnant woman; etoposide, the active moiety of etoposide phosphate is teratogenic in mice and rats advise pregnant women of potential hazard to a fetus; advise women of childbearing potential to avoid becoming pregnant

Advise females of reproductive potential to use effective contraception during treatment and for 6 months after final dose In females of reproductive potential, may cause infertility and result in amenorrhea; premature menopause can occur; recovery of menses and ovulation is related to age at treatment

Lactation: There is no information regarding presence of etoposide in human milk or its effects on breastfed infant milk production; because of potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment with etoposide

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Appears to inhibit or alter DNA replication, induces G2-phase arrest & preferentially kills cells in G2 & late S phases

Pharmacokinetics

Bioavailability: 25-75%

Protein bound: 94-98%

Vd: 7-17 L/m²

Metabolism: Liver

Half-Life: 4-11 hr

Peak plasma time: 1 hr

Peak plasma concentration: 4.7 mcg/mL

Clearance: 13.4 mL/min

Excretion: Urine (35%)

IV Incompatibilities

Etoposide

• Y-site: cefepime, filgrastim, idarubicin

Etoposide PO4

• Y-site: amphotericin B, cefepime, chlorpromazine, imipenem-cilastatin, methylprednisolone, mitomycin, prochlorperazine

IV Compatibilities

Etoposide

• Additive: carboplatin, cisplatin, cisplatin/cyclophosphamide, cytarabine/daunorubicin, doxorubicin/vincristine (may lose some compatibility at high concentration of all 3 drugs), floxuridine, fluorouracil, hydroxyzine, ifosfamide, mitoxantrone, ondansetron
• Y-site: allopurinol, amifostine, aztreonam, cladribine, doxorubicin liposomal, fludarabine, melphalan, methotrexate, mitoxantrone, ondansetron, paclitaxel, piperacillin-tazobactam, sargramostim, NaHCO3, teniposide, thiotepa, topotecan, vinorelbine

Etoposide PO4

• Additive: doxorubicin/vincristine
• Y-site (partial list): acyclovir, amikacin, ampicillin, ampicilin-sulbactam, most cephalosporins (except cefepime), cisplatin, ciprofloxacin, clindamycin, cytarabine, cyclophosphamide, dactinomycin, daunorubicin, diphenhydramine, dobutamine, dopamine, doxorubicin, droperidol, fluconazole, fluorouracil, furosemide, heparin, idarubicin, linezolid, MgSO4, methotrexate, metoclopramide, mitoxantrone, morphine, ondansetron, paclitaxel, KCl, NaHCO3, vancomycin, vinblastine, vincristine, zidovudine

IV Preparation

VePesid, Toposar & equivalents

• Concs >0.4 mg/mL are very unstable
• Lower dose regimens (<1 g/dose): doses may be diluted in 100-1000 mL of D5W or NS
• High dose regimens (>1 g/dose): draw total dose into an empty Viaflex container and add appropriate amount of diluent for a final concentration of 1 mg/mL

• High dose, 2-Channel Pump Method

  • Instill all of the etoposide dose into one Viaflex container for a concentration of 20 mg/mL
  • Infuse this into one channel (any 2-channel infusion pump that does not require a hard plastic cassette)
  • Infuse indicated diluent (D5W or NS) at least 20x infusion rate of etoposide to simulate a 1 mg/mL concentration in the line
  • Etoposide should be Y-sited into the port most proximal to patient
  • Attach 0.22 micron filter to line after Y-site and before entry into patient

Etopophos

• Reconstitute to 10-20 mg/mL with any one of: D5W; NS; SWI; BWI; bacteriostatic NS
• May be further diluted down to 0.1 mg/mL with NS or D5W

IV Administration

VePesid, Toposar & equivalents

• Administer lower doses IVPB over at least 30 min to minimize the risk of hypotensive reactions
• Administer high doses via 2-channel pump method; in-line 0.22 micron filter should be attached to ALL etoposide infusions due to the high potential for precipitation
• Monitor for crystallization

Etopophos

• Infuse over 5-210 min

Extravasation Management

Treatment necessary only if large amount of conc soln extravasates

Terminate injection or infusion immediately and aspirate back as much as possible

Apply warm pack for 15-20 min QID and elevate

May cause phlebitis, urticaria or redness

Storage

Store intact vials at room temp and protected from light