Etoposide (Monograph)
Brand names: Etopophos, Toposar, VePesid
Drug class: Antineoplastic Agents
VA class: AN900
Chemical name: [5R-[5α,5aβ,8aα,9β(R*)]]-9-[4,6-O-ethylidene-β-d-glucopyranosyl)oxy]5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3′,4′:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one
Molecular formula: C29H32O13
CAS number: 33419-42-0
Warning
Introduction
Antineoplastic agent; semisynthetic podophyllotoxin-derivative.1 2 3
Uses for Etoposide
Testicular Cancer
Component of various combination chemotherapeutic regimens for treatment of refractory testicular tumors in patients who have already received appropriate surgery, chemotherapy, and radiation therapy.1 256
Component of various combination chemotherapeutic regimens with cisplatin for first-line treatment of stage III or unresectable stage II nonseminomatous testicular carcinoma39 40 41 42 206 and for chemotherapy-refractory disease.2 38 39 43 44 165 182
Combination chemotherapy with etoposide, cisplatin, and bleomycin (BEP) is recommended for initial treatment of advanced nonseminomatous testicular carcinoma.198 206 207 208 209 210 211 212 213
Component of a combination chemotherapeutic regimen (ifosfamide, cisplatin, and either etoposide or vinblastine) as second-line therapy for recurrent nonseminomatous testicular carcinoma.223 241 243 244 245 246 247
Component of combination chemotherapeutic regimens (with cisplatin) for initial treatment of disseminated seminoma testis45 50 51 198 214 and treatment-refractory disease.38 43
Component of combination chemotherapeutic regimens (usually with cisplatin) for initial treatment of advanced extragonadal germ-cell tumors.52
Small Cell Lung Cancer
Component of a combination chemotherapeutic regimen with etoposide and cisplatin or carboplatin (PE) as a preferred first-line treatment of small-cell lung cancer.a 65 79 80 81 82 83 84 180 183 215 253
In combination with ifosfamide with mesna and cisplatin (VIP) or carboplatin (ICE)215 249 250 252 253 254 255 as second-line therapy for the treatment of refractory small-cell lung cancer.65 81 82 83 183 215 249 250 252 253 254 255
In combination with cyclophosphamide and doxorubicin (or vincristine)61 69 70 71 72 73 86 190 199 200 201 for treatment of extensive-stage disease.253
Non-small Cell Lung Cancer
Combination chemotherapy with etoposide and cisplatin has been used for second-line treatment of advanced non-small cell lung cancer† [off-label],93 94 95 96 204 205 but paclitaxel-containing 215 237 301 302 or other platinum-based regimens215 237 currently are preferred.
Hodgkin’s Disease
Component of combination chemotherapeutic regimens for treatment of advanced or refractory Hodgkin’s lymphoma† [off-label].a 14 64 100 101 110 116 118 119 121 123 129
Non-Hodgkin’s Lymphoma
Component of various combination chemotherapeutic regimens for treatment of advanced non-Hodgkin’s lymphoma† [off-label].13 14 54 64 100 101 115 116 117 118 119 120
Component of combination chemotherapeutic regimens (e.g., etoposide, ifosfamide, and methotrexate) for treatment of advanced diffuse lymphomas of unfavorable histology (e.g., diffuse histiocytic lymphoma)† [off-label].54 100 101 115 117 118 120 121 122 123 124 125 126 127
Cutaneous T-cell Lymphoma
Has been used with transient responses in patients with cutaneous T-cell lymphoma (mycosis fungoides† [off-label]).128
Acute Myeloid Leukemia
Used alone54 100 101 102 103 104 105 106 107 108 109 110 and in various combination chemotherapeutic regimens11 107 108 111 112 for treatment of refractory acute myeloid (myelogenous, nonlymphocytic) leukemia (AML, ANLL)† in adults and children.14 34 54 67 100 101 102 103 104 105 106 107 108 109 110
Particularly effective for the treatment of acute monocytic and myelomonocytic leukemias†;34 54 100 101 102 103 104 107 110 may be useful when monocytoid cells are not cleared with conventional combination chemotherapy.100 101 102 103 104 107 110
Acute Lymphocytic Leukemia
Has been used alone and in combination chemotherapy for remission induction in refractory acute lymphocytic (lymphoblastic) leukemia (ALL)† in a limited number of children;108 109 110 little, if any, activity in adults.100 101 107
Wilms’ Tumor
Component of a combination chemotherapeutic regimen (e.g., carboplatin with etoposide) as second-line (salvage) therapy for treatment of recurrent (relapsed or refractory) Wilms’ tumor†231 232 234 235 including recurrent tumors of unfavorable histology, abdominal recurrence after radiation therapy, or recurrence within 6 months of nephrectomy or after initial combination chemotherapy.231 232 239
Alternative to standard preferred regimens in patients with less severe stages of Wilms’ tumor†.215
Second-line high-dose therapy followed by autologous bone marrow transplantation also has been used effectively in recurrent disease.231 232
Offer patients with recurrent disease (i.e., salvage therapy failure) treatment under protocol conditions in ongoing clinical trials.231
Neuroblastoma
Component of combination chemotherapeutic regimens (cyclophosphamide, doxorubicin, cisplatin, and/or etoposide or teniposide) as preferred first-line therapy for neuroblastoma†.a 64 109 110 157 215 226 227 228 239
Kaposi’s Sarcoma
Used alone or in combination chemotherapeutic regimens257 258 259 as second-line therapya 133 215 258 for palliative treatment of AIDS-related Kaposi’s sarcoma†.215
Ovarian Cancer
Has been used orally as second-line therapy for advanced epithelial ovarian cancer†.a 215 312 313 314 315 316
Component of a combination chemotherapeutic regimen with bleomycin and cisplatin (BEP) as first-line therapy for ovarian germ cell tumors†.215 317 a
Other Uses
Component of alternating chemotherapeutic regimens (vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and mesna and etoposide) as first-line therapy for Ewing’s sarcoma†.a 54 110 157
Component of a chemotherapeutic regimen with methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO), or with cisplatin as second-line therapy for gestational trophoblastic tumors† (choriocarcinoma†).a Also has been used for treatment of chorioadenoma destruens†.130 185 a
May be useful for treatment of hepatoma†.110 131 132
May be useful as second-line therapy for treatment of rhabdomyosarcoma†.a 64 109 110
Related/similar drugs
Tecvayli, methotrexate, Keytruda, carboplatin, pembrolizumab, fluorouracil, Avastin
Etoposide Dosage and Administration
General
-
Consult specialized references for procedures for proper handling and disposal of antineoplastics.b c d (See IV Administration under Dosage and Administration.)
Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer orally189 or IV.1 189 256
Intraperitoneal and intrapleural administration is not recommended; delayed, severe (sometimes fatal) toxicity has occurred in animals following administration by these routes.139 155
Observe closely for possible hypotensive or anaphylactoid reactions during administration of the drug.1 (See Hypotension and also see Sensitivity Reactions, under Cautions.)
Oral Administration
Administer etoposide capsules orally.c
IV Administration
Administer diluted etoposide concentrate for injection by slow IV infusion.1 189
Administer etoposide phosphate by IV infusion.256
Use syringes with Luer-Lok fittings for handling of etoposide concentrate for injection;2 under pressure, needles have become displaced from etoposide-containing syringes without Luer-Lok fittings.2
Plastic devices composed of acrylic or ABS (a polymer composed of acrylonitrile, butadiene, and styrene) may crack and leak when used with undiluted etoposide injection.189
Etoposide solutions containing 0.1–0.4 mg/mL in 0.9% sodium chloride or 5% dextrose injection have been filtered through several commercially available filters (e.g., 0.22-µm Millex-GS or Millex-GV) without filter decomposition.2 159
Reconstitution
Reconstitute vial containing 100 mg of etoposide phosphate powder with 5 or 10 mL sterile water for injection, 5% dextrose injection, 0.9% sodium chloride, bacteriostatic water for injection (with benzyl alcohol), or bacteriostatic sodium chloride for injection (with benzyl alcohol) to provide a solution containing 20 mg etoposide per mL (22.7 etoposide phosphate per mL) or 10 mg etoposide per mL (11.4 mg etoposide phosphate per mL), respectively.256
May administer reconstituted etoposide phosphate with or without further dilution.256
Dilution
Etoposide concentrate for injection must be diluted before administration.1 2 5 189
Dilute required dose of concentrate for injection to a final concentration of 0.2 or 0.4 mg/mL in 0.9% sodium chloride or 5% dextrose injection.1 2
Reconstituted etoposide phosphate solutions may be further diluted with either 5% dextrose injection or 0.9% sodium chloride injection to concentrations as low as 0.1 mg of etoposide per mL.256
Rate of Administration
Do not administer etoposide solutions by rapid IV injection.1 (See Hypotension under Cautions.)
Administer etoposide IV infusions over at least 30–60 minutes to minimize the risk of hypotensive reactions.1 If hypotensive reaction occurs, use slower rate of infusion if restarting after discontinuance and appropriate treatment.1 2
A longer duration of administration may be used if the volume of fluid to be infused is a concern.189
Has been administered by continuous IV infusion over 5 days,134 135 136 but no therapeutic advantage with this method over intermittent IV infusions.156
May administer etoposide phosphate solutions over 5–210 minutes.256
Dosage
Available as etoposide and etoposide phosphate; dosage is expressed in terms of etoposide; 113.6 mg of etoposide phosphate is equivalent to 100 mg of etoposide.296
Base dosage on the clinical and hematologic response and tolerance of the patient and whether or not other chemotherapy or radiation therapy has been or is also being used in order to obtain optimum therapeutic results with minimum adverse effects.1 2
Consult published protocols for the dosage, method, and sequence of administration of etoposide and other chemotherapeutic agents used in combination chemotherapeutic regimens.b
Do not administer a repeat course until the patient’s hematologic function is within acceptable limits.1
Toxicity profile of etoposide phosphate infused at doses exceeding 175 mg/m2 has not been delineated.256
Adults
Testicular Cancer
Induction of Remission for Refractory Testicular Neoplasms
IVCombination chemotherapy regimens: Usually, 50–100 mg/m2 daily for 5 consecutive days every 3–4 weeks or 100 mg/m2 daily on days 1, 3, and 5 every 3–4 weeks,1 for 3 or 4 courses of therapy.38 43 44
When the consecutive-day dosage regimen is employed, some clinicians administer etoposide for 3–5 days, depending on the patient’s hematologic tolerance.38 43
Small Cell Lung Cancer
Oral
Twice the IV dosage rounded to the nearest 50 mg is recommended.189
IV
Combination chemotherapy regimens: Usually, ranges from 35 mg/m2 daily for 4 consecutive days to 50 mg/m2 daily for 5 consecutive days, every 3–4 weeks.188 256
Optimum duration not clearly defined; no additional improvement in survival when duration of therapy >3–6 months for limited-stage or >6 months for extensive-stage disease.253
Kaposi’s Sarcoma
AIDS-Related Kaposi’s Sarcoma†
IV150 mg/m2 daily for 3 consecutive days every 4 weeks; repeat cycles of therapy and reduce dosage as necessary depending on the patient’s response and the myelosuppressive effect of the drug.133
Special Populations
Hepatic Impairment
Use with caution; consider the need for dosage reduction.159 163 176
Renal Impairment
Clcr >50 mL/minute: no initial dose modification required.256
Clcr 15–50 mL/minute: administer 75% of the initial recommended dose.256
Clcr <15 mL/minute: consider further dose reduction; specific data are not available.256
Base subsequent doses on patient tolerance and clinical effect.256
Cautions for Etoposide
Contraindications
-
Known hypersensitivity to etoposide, etoposide phosphate, or any ingredient in the formulations.1 2 189 256
Warnings/Precautions
Warnings
Myelosuppression
Risk of dose-limiting and potentially fatal myelosuppression,1 2 17 59 64 106 110 116 118 120 133 134 135 136 256 manifested commonly by leukopenia (principally granulocytopenia);1 2 17 57 59 64 67 91 100 101 256 thrombocytopenia 1 2 17 64 67 91 100 101 and anemia may also occur.17 60 64 133 189 Severe myelosuppression with resulting infection or bleeding may occur.1 2 92 100 105 118 120 133 134 135 136
Granulocyte and platelet nadirs usually occur within 7–14 and 9–16 days, respectively, after administration of etoposide,1 2 59 67 106 134 136 and within 12–19 and 10–15 days, respectively, after administration of etoposide phosphate;256 leukocyte nadir usually occurs within 15–22 days after administration of etoposide phosphate.256 Bone marrow recovery is usually complete within 20 days after administration,1 2 56 60 67 134 135 but may occasionally require longer periods.17 106 136
Monitor hematologic function frequently during and after treatment.1 2 Perform CBC (leukocyte count with differential, platelet count, hemoglobin) prior to initiation of therapy, at appropriate intervals during the course of treatment (e.g., twice weekly),180 and before each subsequent course of treatment.1 2
Suspend therapy if the platelet count is <50,000/mm3 or absolute neutrophil count is <500/mm3.1 2 Resume therapy when blood counts have returned to an acceptable level, if indicated.1 2
If severe hematologic toxicity occurs, consider supportive therapy, antibiotics for complicating infections, and blood product transfusions.105 133 135 136
Hypotension
Transient hypotension reported following rapid IV administration of etoposide.1 2 57 110
Observe closely for possible hypotensive reactions.1
Administer IV infusions slowly (i.e., over at least 30–60 minutes) to minimize the risk of hypotensive reactions.1
Hypotension occurring during administration usually subsides with infusion discontinuance, administration of IV fluids or other supportive therapy as necessary.1 2
Use slower rate of infusion if restarting after discontinuance and appropriate treatment.1 2
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.c d Avoid pregnancy during therapy.c d If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.c d
Carcinogenicity
Acute leukemia (with or without a preleukemic phase) has been reported rarely in patients receiving etoposide in association with other antineoplastic agents.189 256
Animal studies to determine the carcinogenic potential of etoposide have not been performed to date;1 256 however, the drug should be considered a potential carcinogen.1
Sensitivity Reactions
Hypersensitivity Reactions
Anaphylactoid reactions consisting principally of chills,1 2 67 92 256 rigors,256 diaphoresis,64 256 pruritus,256 loss of consciousness,256 nausea,256 vomiting,256 fever,1 2 bronchospasm,1 2 178 256 dyspnea,1 2 141 178 256 tachycardia,1 2 256 hypertension,189 256 and/or hypotension1 2 92 178 256 reported.1 2 67 92 134 178 256
Observe closely for possible anaphylactic reactions.1
Appropriate equipment for maintenance of an adequate airway and other supportive measures and agents for the treatment of these reactions should be readily available whenever etoposide is administered.1
Stevens-Johnson syndrome,256 rash,1 2 189 256 pigmentation,189 urticaria,189 256 and severe pruritus64 189 256 occur infrequently.1 2 142 179
If a hypersensitivity reaction occurs during administration, discontinue infusion and institute appropriate therapy (e.g., antihistamines, epinephrine, oxygen, corticosteroids) as necessary.1
The role of infusion concentration or rate in the development of hypersensitivity reactions is uncertain.189 256
General Precautions
Toxicity
Highly toxic drug with a low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.1 2 34 139
Administer only under constant supervision by clinicians experienced in therapy with cytotoxic agents and only when the potential benefits outweigh the possible risks.1
Most adverse effects are reversible if detected promptly.1
Discontinue or reduce dosage and institute appropriate measures as necessary when severe adverse effects occur.1
Reinstitute therapy with caution, considering further need for the drug and possible toxicity recurrence.1
Specific Populations
Pregnancy
Category D.c (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether etoposide is distributed into milk.1 Discontinue nursing or the drug.1
Pediatric Use
Safety and efficacy not established.1 256
Higher rates of anaphylactoid reactions reported in children receiving infusions at higher than recommended concentrations.189 256 (See Hypersensitivity Reactions under Cautions.)
Has been used with encouraging results for refractory acute myelogenous leukemia†,11 108 109 110 112 has shown some activity against refractory acute lymphocytic leukemia†108 110 and other pediatric malignancies†,109 110 157 but additional evaluation is needed.108 109 110 157
Each mL of etoposide concentrate for injection contains 30 mg of benzyl alcohol.c Although a causal relationship has not been established, injections preserved with benzyl alcohol have been associated with toxicity in neonates.216 217 218 219 220 221
Concentrate for injection contains polysorbate 80A complex; potentially fatal syndrome (e.g., thrombocytopenia, ascites, and renal, pulmonary, and hepatic failure) has occurred in several premature infants who received a vitamin E product (IV) with polysorbate 80.189
Hepatic Impairment
Effects of hepatic impairment on etoposide elimination have not been fully evaluated.20 21 28 163 176 197
Toxicity of rapidly infused etoposide phosphate in hepatic impairment has not been adequately evaluated.256
Use with caution, consider the need for dosage reduction; more severe hematologic toxicity reported with elevated serum bilirubin concentrations in one study.163 Some evidence of reduced total plasma clearance and elimination.28 159 163 176
Renal Impairment
Dosage adjustments recommended based on degree of renal impairment.20 21 161 256 (See Renal Impairment under Dosage and Administration.)
Toxicity of rapidly infused etoposide phosphate in renal impairment has not been adequately evaluated.256
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether safety and efficacy for treatment of testicular tumors in geriatric patients differ from safety and efficacy in younger adults.f
Response in patients ≥65 years of age with small cell lung cancer similar to that in younger adults.f
Substantially eliminated by kidneys; assess renal function periodically since geriatric patients more likely to have decreased renal function.f Dosage adjustments may be required.f (See Renal Impairment under Dosage and Administration.)
Geriatric patients may be particularly susceptible to etoposide-induced adverse effects.137
Common Adverse Effects
Leukopenia,1 2 17 57 59 64 67 91 100 101 256 thrombocytopenia,1 2 17 64 67 91 100 101 neutropenia,256 anemia,17 60 64 133 189 nausea,1 2 17 60 67 91 100 109 189 256 vomiting,1 2 17 60 67 91 100 109 189 256 anorexia,1 2 67 92 101 116 134 256 mucositis,256 diarrhea,1 2 109 134 136 256 alopecia,1 2 17 60 64 67 100 101 109 133 134 189 256 asthenia/malaise,c fatigue,1 2 chills and/or fever.c
Drug Interactions
Specific Drugs
|
Drug |
Interaction |
Comments |
|---|---|---|
|
Antineoplastic agents (cisplatin, carmustine, cytarabine, cyclophosphamide) |
Potential additive or synergistic antineoplastic activity43 44 65 79 80 81 82 83 152 153 154 |
|
|
Cisplatin |
Possible decreased etoposide elimination176 |
Limited data, further documentation needed; consider potential effect when administering etoposide to patients who received prior cisplatin therapy176 |
|
Cyclosporine (high-dose) |
Possible decreased total body clearance of etoposide with concomitant use of oral etoposide and high-dose cyclosporine 256 |
|
|
Inhibitors of phosphatase activity (e.g., levamisole HCl) |
Use caution with etoposide phosphate256 |
Etoposide Pharmacokinetics
Absorption
Bioavailability
Oral capsules: about 50% (range: 25–75%).17 18 19 160 161 189 190 191 192 193 194 195 196 197
Distribution
Extent
Not fully characterized.18 21 24 27 28 Following IV administration, distributed minimally into pleural fluid21 27 and has been detected in the saliva,197 liver,173 spleen,173 kidney,173 myometrium,189 197 healthy brain tissue,27 and brain tumor tissue.27 175
Does not readily penetrate the CNS;1 18 21 22 27 29 30 197 variable CSF concentrations generally ranging from undetectable18 22 to <5% of concurrent plasma concentrations21 29 30 162
Apparently crosses the placenta in animals,1 2 not known whether distributed into milk.1
Plasma Protein Binding
Approximately 97% at 10 mcg/mL in vitro.c f
Elimination
Metabolism
Metabolized principally to inactive hydroxy acid21 25 26 30 32 33 177 (probably the trans-hydroxy acid).33
Elimination Route
Following IV infusion, excreted principally (40–60%) in urine as unchanged drug (20–30% within 24 hours,18 29 30 30–45% within 48 hours)20 161 and metabolites in 48–72 hours.18 20 21 26 27 29 30 32 2–16% is excreted in feces within 72 hours;29 30 .28 173 174 197
Following oral administration, about 5–25% of the dose is excreted in urine within 24–48 hours.191 194 195 196 197
Half-life
Biphasic,18 21 22 24 25 27 29 30 31 176 197 may exhibit triphasic elimination with a prolonged terminal phase.19 197
In adults, 0.6–2 hours (range: 0.2–2.5 hours) in the initial phase and 5.3–10.8 hours (range: 2.9–19 hours) in the terminal phase.18 20 21 24 29 161 189 191 192
In children, 0.6–1.4 hours in the initial phase and 3–5.8 hours in the terminal phase.18 22 25 31
Special Populations
The effects of renal impairment on elimination have not been fully evaluated,20 21 28 163 176 197 but a substantial fraction of the drug is excreted unchanged in urine;18 20 21 29 30 161 176 256 consider dosage reductions.b (See Renal Impairment under Dosage and Administration.)
Stability
Storage
Oral
Capsules
2–8°C.189 Do not freeze.c Stable for 2 years refrigerated at 2–8°C.189
Parenteral
Etoposide Injection Concentrate for IV Infusion
Room temperature (25°C).1 Stable for 2 years unopened at room temperature.1
Following dilution to concentrations of 0.2 or 0.4 mg/mL, stable for 96 or 24 hours, respectively, at 25°C under normal room fluorescent light in glass or plastic containers.c
Etoposide Phosphate Lyophilized Powder for Injection
2–8°C; store in unopened vials in original package to protect from light;256 296 stable at least 36 months.296
Following reconstitution, 10 or 20 mg/mL solutions of etoposide phosphate in sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection, bacteriostatic water for injection (with benzyl alcohol) or bacteriostatic sodium chloride for injection (with benzyl alcohol) are stable for 7 days at 2–8°C in glass or plastic containers.d
10 or 20 mg/mL solutions of etoposide phosphate in sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection are stable for 24 hours at 20–25°C.d
10 or 20 mg/mL solutions of etoposide phosphate in bacteriostatic water for injection (with benzyl alcohol) or bacteriostatic sodium chloride for injection (with benzyl alcohol) are stable for 48 hours at 20–25°C.d
Etoposide phosphate solutions further diluted in 5% dextrose injection or 0.9% sodium chloride injection are stable for 24 hours at 2–8°C or 20–25°C.d
Compatibility
Parenteral
Injection Concentrate for IV Infusion
Crystallization in aqueous solutions appears to be concentration dependent and may occur following dilution because etoposide is sparingly soluble in water;1 2 5 discard if crystallization occurs.5
Solutions of etoposide prepared at concentrations >0.4 mg/mL may precipitate; 189 concentration >0.4 mg/mL not recommended.1 2 189 c
1 mg/mL solutions in 5% dextrose injection or 0.9% sodium chloride have crystallized etoposide within 5 minutes upon stirring or within 30 minutes upon allowing the solution to stand;5 1 mg/mL solutions not recommended.5
Solution CompatibilityHID (etoposide)
|
Compatible |
|---|
|
Dextrose 5% in water |
|
Ringer’s injection, lactated |
|
Variable |
|
Sodium chloride 0.9% |
Drug Compatibility (etoposide)
|
Compatible |
|---|
|
Carboplatin |
|
Cisplatin |
|
Cisplatin with cyclophosphamide |
|
Cisplatin with floxuridine |
|
Cytarabine with daunorubicin HCl |
|
Floxuridine |
|
Fluorouracil |
|
Hydroxyzine HCl |
|
Ifosfamide |
|
Ifosfamide with cisplatin |
|
Mitoxantrone HCl |
|
Ondansetron HCl |
|
Variable |
|
Cisplatin with mannitol and potassium chloride |
|
Doxorubicin HCl with vincristine sulfate |
|
Compatible |
|---|
|
Allopurinol sodium |
|
Amifostine |
|
Aztreonam |
|
Cladribine |
|
Doxorubicin HCl liposome injection |
|
Fludarabine phosphate |
|
Gemcitabine HCl |
|
Granisetron HCl |
|
Melphalan HCl |
|
Methotrexate sodium |
|
Micafungin sodium |
|
Mitoxantrone HCl |
|
Ondansetron HCl |
|
Paclitaxel |
|
Piperacillin sodium–tazobactam sodium |
|
Sargramostim |
|
Sodium bicarbonate |
|
Teniposide |
|
Thiotepa |
|
Topotecan HCl |
|
Vinorelbine tartrate |
|
Incompatible |
|
Filgrastim |
|
Gallium nitrate |
|
Idarubicin HCl |
Solution CompatibilityHID (etoposide phosphate)
|
Compatible |
|---|
|
Dextrose 5% in water |
|
Sodium chloride 0.9% |
Drug Compatibility (etoposide phosphate)
|
Compatible |
|---|
|
Doxorubicin HCl with vincristine sulfate |
|
Compatible |
|---|
|
Acyclovir sodium |
|
Amikacin sulfate |
|
Aminophylline |
|
Ampicillin sodium |
|
Ampicillin sodium–sulbactam sodium |
|
Anidulafungin |
|
Aztreonam |
|
Bleomycin sulfate |
|
Bumetanide |
|
Buprenorphine HCl |
|
Butorphanol tartrate |
|
Calcium gluconate |
|
Carboplatin |
|
Carmustine |
|
Caspofungin acetate |
|
Cefazolin sodium |
|
Cefotaxime sodium |
|
Cefotetan disodium |
|
Cefoxitin sodium |
|
Ceftazidime |
|
Ceftriaxone sodium |
|
Cefuroxime sodium |
|
Ciprofloxacin |
|
Cisplatin |
|
Clindamycin phosphate |
|
Co-trimoxazole |
|
Cyclophosphamide |
|
Cytarabine |
|
Dacarbazine |
|
Dactinomycin |
|
Daunorubicin HCl |
|
Dexamethasone sodium phosphate |
|
Diphenhydramine HCl |
|
Dobutamine HCl |
|
Dopamine HCl |
|
Doripenem |
|
Doxorubicin HCl |
|
Doxycycline hyclate |
|
Droperidol |
|
Enalaprilat |
|
Famotidine |
|
Floxuridine |
|
Fluconazole |
|
Fludarabine phosphate |
|
Fluorouracil |
|
Furosemide |
|
Ganciclovir sodium |
|
Gemcitabine HCl |
|
Gentamicin sulfate |
|
Granisetron HCl |
|
Haloperidol lactate |
|
Heparin sodium |
|
Hydrocortisone sodium succinate |
|
Hydromorphone HCl |
|
Hydroxyzine HCl |
|
Idarubicin HCl |
|
Ifosfamide |
|
Leucovorin calcium |
|
Linezolid |
|
Lorazepam |
|
Magnesium sulfate |
|
Mannitol |
|
Meperidine HCl |
|
Mesna |
|
Methotrexate sodium |
|
Metoclopramide HCl |
|
Metronidazole |
|
Mitoxantrone HCl |
|
Morphine sulfate |
|
Nalbuphine HCl |
|
Ondansetron HCl |
|
Oxaliplatin |
|
Paclitaxel |
|
Piperacillin sodium–tazobactam sodium |
|
Potassium chloride |
|
Promethazine HCl |
|
Ranitidine HCl |
|
Sodium bicarbonate |
|
Streptozocin |
|
Teniposide |
|
Thiotepa |
|
Ticarcillin disodium–clavulanate potassium |
|
Tobramycin sulfate |
|
Vancomycin HCl |
|
Vinblastine sulfate |
|
Vincristine sulfate |
|
Zidovudine |
|
Incompatible |
|
Amphotericin B |
|
Cefepime HCl |
|
Chlorpromazine HCl |
|
Imipenem–cilastatin sodium |
|
Methylprednisolone sodium succinate |
|
Mitomycin |
|
Prochlorperazine edisylate |
Actions
-
Exact mechanism(s) of action is not known; apparently produces cytotoxic effects by damaging DNA3 6 7 169 170 and thereby inhibiting or altering DNA synthesis.1 2 3 8 169
-
Induces single-stranded DNA breaks indirectly, possibly through endonuclease activation,6 7 inhibition of intranuclear type II topoisomerase,170 171 172 or formation of a free-radical metabolite via an enzymatic reaction involving the hydroxyl group at the C-4′ position of the E ring.6 7
-
Cell-cycle dependent and cycle-phase specific, inducing G2-phase arrest, and preferentially killing cells in the G2 and late S phases.8 9 10 11 169
-
At 0.3–10 mcg/mL in vitro, cells are inhibited from entering prophase;1 at concentrations of ≥10 mcg/mL, lysis of cells entering mitosis occurs.1 Does not inhibit microtubule assembly.1 2 3 12 167
Advice to Patients
-
Importance of advising patients and/or their parents or guardians of adverse effects and associated manifestations.a
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a
-
Importance of informing patients of other important precautionary information.a (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
|
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|---|---|---|---|---|
|
Oral |
Capsules, liquid-filled |
50 mg |
Etoposide Capsules |
|
|
VePesid |
Bristol-Myers Squibb |
|||
|
Parenteral |
For injection concentrate, for IV infusion only |
20 mg/mL (100, 150, 200, 250, and 500 mg)* |
Etoposide for Injection |
|
|
Toposar |
Pfizer |
|||
|
VePesid |
Bristol-Myers Squibb |
|||
|
20 mg/mL (1 g) pharmacy bulk package* |
Etoposide for Injection |
|||
|
VePesid |
Bristol-Myers Squibb |
|
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|---|---|---|---|---|
|
Parenteral |
For injection |
500 mg (of etoposide) pharmacy bulk package |
Etopophos |
Bristol-Myers Squibb |
|
1 g (of etoposide) pharmacy bulk package |
Etopophos |
Bristol-Myers Squibb |
||
|
For injection, for IV infusion |
100 mg (of etoposide) |
Etopophos |
Bristol-Myers Squibb |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 9, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
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95. Klastersky J, Longeval E, Nicaise C et al. Etoposide and cis-platinum in non-small-cell bronchogenic carcinoma. Cancer Treat Rev. 1982; 9(Suppl. A):133-8. http://www.ncbi.nlm.nih.gov/pubmed/6889918?dopt=AbstractPlus
96. Veronesi A, Zagonel V, Santarossa M et al. cis-Platinum and etoposide combination chemotherapy of advanced non-oat cell bronchogenic carcinoma. Cancer Chemother Pharmacol. 1983; 11:35-7. http://www.ncbi.nlm.nih.gov/pubmed/6683999?dopt=AbstractPlus
97. Eagan RT, Creagan ET, Ingle JN et al. VP-16, cyclophosphamide, adriamycin, and cis-platinum (V:CAP-I) in patients with metastatic adenocarcinoma of the lung. Tumori. 1979; 65:105-9. http://www.ncbi.nlm.nih.gov/pubmed/442215?dopt=AbstractPlus
98. Eagan RT, Frytak S, Nichols WC et al. Evaluation of VP-16-213, cyclophosphamide, doxorubicin, and cisplatin (V-CAP) in advanced large cell lung cancer. Cancer Treat Rep. 1981; 65:715-7. http://www.ncbi.nlm.nih.gov/pubmed/6166376?dopt=AbstractPlus
99. Fuks JZ, Aisner J, Van Echo DA et al. Randomized study of cyclophosphamide, doxorubicin, and etoposide (VP16-213) with or without cisplatinum in non-small cell lung cancer. J Clin Oncol. 1983; 1:295-301. http://www.ncbi.nlm.nih.gov/pubmed/6686849?dopt=AbstractPlus
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