etoposide (VePesid, Toposar, Etopophos, vp 16)
Dosing and uses of VePesid, Toposar (etoposide)
Adult dosage forms and strengths
capsule
- 50mg
injectable solution
- 20mg/mL
powder for injection
- 100mg
Testicular Cancer
50-100 mg/m²/day IV on days 1-5, Or
100 mg/m²/day IV on days 1, 3, 5
Repeat q3-4week
Small-Cell Lung Cancer
35 mg/m²/day IV for 4 days, Or
50 mg/m²/day IV for 5 days; repeat q3-4week
Monitor
CBC, Hgb, LFTs, renal function
Administration
Equivalent IV doses for etoposide & etoposide phosphate
PO: 2 times IV dose, rounded to nearest 50 mg
Renal Impairment
CrCl >50 mL/min: Dose adjustment not necessary
CrCl 15-50 mL/min: 75% of regular dose
CrCl < 15 mL/min: Not studied; consider further dose reductions
Hepatic Impairment
Not studied
Pediatric dosage forms and strengths
capsule
- 50mg
injectable solution
- 20mg/mL
powder for injection
- 100mg
AML Induction (Off-label)
<3 years: 3.3 mg/kg/day IV continuous infusion for 4 days
≥3 years: 100 mg/m²/day IV continuous infusion for 4 days
VePesid, Toposar (etoposide) adverse (side) effects
>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
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Severe myelosuppression, which could result in bleeding and infection, may occur
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
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, discontinue drug or do not nurse
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.
Pharmacology of VePesid, Toposar (etoposide)
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%)
Administration
IV Incompatibilities (Etoposide)
Y-site: cefepime, filgrastim, idarubicin
IV Incompatibilities (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 conc 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
IV Compatibilities (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 & 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/mLInfuse 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 lineEtoposide should be Y-sited into the port most proximal to ptAttach 0.22 micron filter to line after Y-site & before entry into pt
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 e high potential for precipitation
- Monitor for crystallization
Etopophos
- Infuse over 5-210 min
Extravasation Management
Tx necessary only if large amount of conc soln extravasates
Terminate injection or infusion immediately & aspirate back as much as possible
Apply warm pack for 15-20 min QID & elevate
May cause phlebitis, urticaria or redness
Storage
Store intact vials at room temp & protected from light
