Version July 2025
Etoposide should be administered under the supervision of a qualified health care provider experienced in the use of cancer chemotherapeutic agents.
Severe myelosuppression, with resulting infection or bleeding, may occur.
Note: Dose, frequency, number of doses, and start date may vary by protocol and treatment phase; refer to individual protocols. Pediatric dosing units (eg, mg/kg, mg/m2) and routes (eg, IV, continuous IV infusion, intraventricular) are variable depending upon protocol/regimen; use caution. Etoposide is associated with a low emetic risk (intravenous) and moderate emetic risk (oral); antiemetics may be recommended to prevent nausea and vomiting (Ref).
Acute lymphoblastic leukemia (ALL), relapsed/refractory: Limited data available:
Hijiya 2011: Induction and Consolidation: Children and Adolescents: IV: 100 mg/m2 over 2 hours for 5 consecutive days in Induction (in combination with cyclophosphamide and clofarabine) and 4 consecutive days in Consolidation (in combination with cyclophosphamide and clofarabine).
Parker 2010: ALL R3 Protocol:
Children and Adolescents:
Phase 2 Consolidation: IV: 100 mg/m2 once daily on days 15 to 19 (in combination with other chemotherapeutic agents).
Phase 5 before continuation: IV: 150 mg/m2 once daily on days 42, 49, 99, and 106 (in combination with other chemotherapeutic agents).
Acute lymphoblastic leukemia (ALL) of infancy: Limited data available:
Dreyer 2011; Dreyer 2015: Infants and Children <1 year at diagnosis: IV: 100 mg/m2 over 2 hours once daily for 5 consecutive days; specific regimen days and combination chemotherapeutic agents variable dependent on protocol phase; refer to specific protocols.
Tomizawa 2020: Note: Specific regimen days and combination chemotherapeutic agents variable dependent on protocol phase.
Infants and Children <1 year at diagnosis:
Low risk; Regimen A:
Early consolidation and re-induction: Note: Used in combination with other chemotherapy; varies with phase of the regimen (refer to specific protocols).
Infants <2 months: IV: 66.7 mg/m2 over 2 hours once daily for 4 consecutive days.
Infants ≥2 to 3 months: IV: 75 mg/m2 over 2 hours once daily for 4 consecutive days.
Infants >3 months and Children: IV: 100 mg/m2 over 2 hours once daily for 4 consecutive days.
Maintenance:
Infants <2 months: IV: 100 mg/m2 over 2 hours once daily on days 14 and 42.
Infants ≥2 to 3 months: IV: 112.5 mg/m2 over 2 hours once daily on days 14 and 42.
Infants >3 months and Children: IV: 150 mg/m2 over 2 hours once daily on days 14 and 42.
Intermediate and high risk; Regimen B:
Early and late consolidation and maintenance B-I (cycles 2 and 4):
Infants <2 months: IV: 66.7 mg/m2 over 2 hours once daily for 5 consecutive days.
Infants ≥2 to 3 months: IV: 75 mg/m2 over 2 hours once daily for 5 consecutive days.
Infants >3 months and Children: IV: 100 mg/m2 over 2 hours once daily for 5 consecutive days.
Acute myeloid leukemia (AML): Limited data available:
Gamis 2014: Note: Some aspects of protocol dosing presented in previous reports (Ref).
Infants, Children, and Adolescents:
Remission Induction: ADE (10 + 3 + 5) and ADE (8 + 3 + 5) regimens:
BSA <0.6 m2: IV: 3.3 mg/kg once daily for 5 days (in combination with cytarabine and daunorubicin).
BSA ≥0.6 m2: IV: 100 mg/m2 once daily for 5 days (in combination with cytarabine and daunorubicin).
Intensification I: AE regimen:
BSA <0.6 m2: IV: 5 mg/kg once daily for 5 days (in combination with cytarabine).
BSA ≥0.6 m2: IV: 150 mg/m2 once daily for 5 days (in combination with cytarabine).
Gibson 2011:
Infants, Children, and Adolescents <17 years: Note: For infants, the full dose was reduced by 25%:
Induction Course 1 (ADE 10 + 3 + 5, MAE 3 + 10 + 5 regimens):
Infants: IV: 75 mg/m2 once daily for 5 days (in combination with cytarabine and daunorubicin or mitoxantrone).
Children and Adolescents <17 years: IV: 100 mg/m2 once daily for 5 days (in combination with cytarabine and daunorubicin or mitoxantrone).
Induction Course 2 (ADE 8 + 3 + 5, MAE 3 + 8 + 5 regimens):
Infants: IV: 75 mg/m2 once daily for 5 days (in combination with cytarabine and daunorubicin or mitoxantrone).
Children and Adolescents <17 years: IV: 100 mg/m2 once daily for 5 days (in combination with cytarabine and daunorubicin or mitoxantrone).
CNS tumors, malignant (medulloblastoma, primitive neuroectodermal tumors [PNET], ependymoma, and brainstem glioma): Limited data available; multiple regimens reported:
Chi 2004; Fangusaro 2008: Head Start II regimen:
Infants and Children <10 years:
Induction: IV: 4 mg/kg once daily for 2 days on day 2 and 3 of a 21-day cycle (cycle starts on day 0) for 4 to 5 cycles (in combination with cisplatin, vincristine, cyclophosphamide/mesna and high-dose methotrexate/leucovorin).
Consolidation with autologous peripheral blood stem cell rescue: IV: 250 mg/m2 for 3 doses on day −5 to −3 (in combination with carboplatin and thiotepa).
Taylor 2003: Children ≥3 years and Adolescents: IV: 100 mg/m2/dose once daily on days 1, 2, and 3 (in combination with vincristine and carboplatin or cyclophosphamide) every 3 weeks for 4 cycles prior to radiation.
CNS nongerminomatous germ cell tumor (NGGCT): Limited data available:
Children ≥3 years and Adolescents:
Induction Cycles 1, 3, and 5: IV: 90 mg/m2 once daily for 3 days on days 1 to 3 in combination with carboplatin (Ref).
Induction Cycles 2, 4, and 6: IV: 90 mg/m2 once daily for 5 days on days 1 to 5 in combination with ifosfamide (Ref).
CNS tumors; relapsed, metastatic: Limited data available (Ref):
Infants: Intraventricular (using preservative-free formulation): 0.25 mg. Administer via an Ommaya or Rickham reservoir once daily for 5 consecutive days.
Children and Adolescents: Intraventricular (using preservative-free formulation): 0.5 mg Administer via an Ommaya or Rickham reservoir once daily for 5 consecutive days.
Ewing sarcoma: Limited data available; multiple regimens reported:
IE regimen: Children and Adolescents: IV: 100 mg/m2 over 1 hour once daily for 5 days on days 1 to 5 of a 21-day cycle in combination with ifosfamide; frequency of cycles, and alternating chemotherapy combinations vary based on protocol (eg, cyclophosphamide, vincristine, doxorubicin) (Ref).
VAC/IE regimen: Children and Adolescents: IV: 150 mg/m2 once daily for 3 doses on days 1 to 3 in combination with ifosfamide every 3 weeks alternating with VAC (vincristine, doxorubicin, and cyclophosphamide) (Ref).
Relapsed, refractory: ICE regimen: Children and Adolescents: IV: 100 mg/m2 for 5 days every 3 to 4 weeks for up to 12 cycles in combination with carboplatin, ifosfamide, and mesna; or may follow with 2 courses of CAV (cyclophosphamide, doxorubicin, and vincristine) (Ref).
Hematopoietic stem cell transplant (HSCT) conditioning regimen: Limited data available:
Infant ALL conditioning regimen: Infants and Children diagnosed at <1 year: IV: 60 mg/kg/dose over 12 hours on day −4 (in combination with busulfan and cyclophosphamide) (Ref).
ALL conditioning regimen: Infants ≥6 months, Children, and Adolescents: IV: 20 mg/kg once daily on days −4 to −2 (in combination with busulfan and fludarabine) (Ref).
Medulloblastoma conditioning regimen: Children ≥7 years and Adolescents: IV: 250 mg/m2 on days −5, −4, and −3 (in combination with thiotepa and high-dose carboplatin) (Ref).
Hemophagocytic lymphohistiocytosis (HLH): Limited data available:
Infants, Children, and Adolescents:
Initial therapy: IV: 150 mg/m2 twice weekly for weeks 1 and 2 then once weekly for 8 weeks, in combination with cyclosporine and dexamethasone (Ref).
Continuation therapy: IV: 150 mg/m2 every 2 weeks until HSCT or for 40 weeks, in combination with cyclosporine and dexamethasone (Ref).
Hodgkin lymphoma: Limited data available:
High risk: BEACOPP regimen: Children and Adolescents: IV: 200 mg/m2 on days 0, 1, and 2 of a 21-day treatment cycle for 4 cycles (in combination with bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisone, and procarbazine) (Ref).
Intermediate or high risk: ABVE-PC regimen: Children and Adolescents: IV: 125 mg/m2 over 1 hour once daily for 3 days of a 21-day cycle for 2 to 4 cycles (in combination with doxorubicin, vincristine, cyclophosphamide, prednisone, and bleomycin) (Ref).
Lymphoma, primary mediastinal B cell (PMLBL): Limited data available:
Dose adjusted (DA)-EPOCH regimen (Ref):
Children and Adolescents:
Initial: Dose level 1: IV: 50 mg/m2/day on days 1 to 4 as a continuous infusion in combination with doxorubicin, vincristine, cyclophosphamide, and prednisone.
Dosage adjustment: Dose-adjusted for subsequent course every 3 weeks based on neutrophil and platelet counts during nadir to ensure highest tolerated doses are given while minimizing toxicity; within the protocol the dose ranges from 50 mg/m2/day (Level 1) to 124.4 mg/m2/day (Level 6). Measure blood counts twice weekly (3 days apart) (Ref).
Malignant solid tumors, relapsed or metastatic disease:
IE regimen: Children and Adolescents: IV: 100 mg/m2 over 1 hour once daily for 3 to 5 days every 3 weeks in combination with ifosfamide (Ref).
ICE regimen: Children and Adolescents: IV: 100 mg/m2/day for 5 days on days 0 to 4 every 3 weeks for up to 12 cycles in combination with carboplatin, ifosfamide, and mesna (Ref).
Neuroblastoma, high risk: Limited data available:
Children ≥1 year and Adolescents:
Induction: IV: 100 to 200 mg/m2/dose infused over 1 to 2 hours once daily for 3 to 5 consecutive days (in combination with other chemotherapy agents) (Ref); other reported regimens include 100 mg/m2/dose on day 2 and 5 (in combination with cisplatin, doxorubicin, and cyclophosphamide) every 28 days for 5 cycles (Ref).
Myeloablative therapy with stem cell rescue (tandem transplant):
Children <12 kg:
GFR ≥100 mL/minute/1.73 m2: IV: 10 mg/kg over 24 hours × 4 doses in combination with carboplatin and melphalan beginning 7 days prior to stem cell infusion, administered in tandem with thiotepa and cyclophosphamide regimen followed by stem cell rescue (Ref).
GFR ≥60 and <100 mL/minute/1.73 m2: IV: 6.7 mg/kg over 24 hours × 4 doses in combination with carboplatin and melphalan beginning 7 days prior to stem cell infusion, administered in tandem with thiotepa and cyclophosphamide regimen followed by stem cell rescue (Ref).
Children ≥12 kg and Adolescents:
GFR ≥100 mL/minute/1.73 m2: IV: 300 mg/m2 over 24 hours × 4 doses in combination with carboplatin and melphalan beginning 7 days prior to stem cell infusion, administered in tandem with thiotepa and cyclophosphamide regimen followed by stem cell rescue (Ref).
GFR ≥60 and <100 mL/minute/1.73 m2: IV: 200 mg/m2 over 24 hours × 4 doses in combination with carboplatin and melphalan beginning 7 days prior to stem cell infusion, administered in tandem with thiotepa and cyclophosphamide regimen followed by stem cell rescue (Ref).
Retinoblastoma, extraocular: Limited data available:
Infants and Children:
Patient weight <10 kg: IV: 3.3 mg/kg once daily on days 1, 2, and 3 of a 21-day treatment cycle (in combination with carboplatin) alternating cycles with idarubicin and vincristine for a total of 8 cycles (Ref).
Patient weight ≥10 kg: IV: 100 mg/m2 once daily on days 1, 2, and 3 of a 21-day treatment cycle (in combination with carboplatin) alternating cycles with idarubicin and vincristine for a total of 8 cycles (Ref).
Wilms tumor: Limited data available: ICE regimen: Children and Adolescents: IV: 100 mg/m2 once daily for 3 to 5 doses (in combination with ifosfamide and carboplatin); repeat cycle every 21 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.
Adult:
ANC <500/mm3 or platelets <50,000/mm3: Withhold treatment until recovery.
Hypotension: Interrupt infusion and administer IV hydration and supportive care; decrease infusion rate upon reinitiation.
Infusion (hypersensitivity) reactions: Interrupt infusion (medications for the treatment of anaphylaxis should be available for immediate use during etoposide IV administration).
Severe adverse reactions (nonhematologic): Reduce dose or discontinue treatment.
Note: Dosage adjustment may be indication specific; consult institutional protocols.
Infants, Children, and Adolescents: Dosage adjustments are not provided in the manufacturer's labeling for pediatric patients; however, the manufacturer recommends the following for adult patients.
CrCl >50 mL/minute: No adjustment required.
CrCl 15 to 50 mL/minute: Administer 75% of dose.
CrCl <15 mL minute: Data not available; consider further dose reductions.
Alternate adjustments have been recommended (Ref):
GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose.
GFR <10 mL/minute/1.73 m2: Administer 50% of dose.
Hemodialysis/peritoneal dialysis (PD) (after dialysis on dialysis days): Administer 50% of dose.
Continuous renal replacement therapy (CRRT): Administer 75% of dose and reduce for hyperbilirubinemia.
Infants, Children, and Adolescents: The following adjustment has been recommended based primarily on experience in adult patients (Ref):
Bilirubin 1.5 to 3 mg/dL or AST >3 times ULN: Administer 50% of dose.
(For additional information see "Etoposide: Drug information")
Dosage guidance:
Clinical considerations: Refer to the protocol or institutional guidance for additional details of off-label dosing.
Acute lymphoblastic leukemia, relapsed/refractory (off-label use):
IV: 100 mg/m2 on days 1 to 5 (in combination with mitoxantrone, ifosfamide, and mesna) as induction therapy; if complete remission occurred following induction, one additional cycle as consolidation therapy was administered (Ref) or (adults <20 years of age) 100 mg/m2 on days 1 to 5 (in combination with clofarabine and cyclophosphamide) as induction (a second 5-day induction cycle may be administered if a partial response occurred), followed by 100 mg/m2 on days 1 to 4 (in combination with clofarabine and cyclophosphamide) as consolidation; a total of up to 4 cycles (induction and consolidation) may be administered (Ref).
Acute myeloid leukemia, refractory (off-label use):
IV: 80 mg/m2 on days 1 to 6 (in combination with mitoxantrone and cytarabine); if complete remission occurred following induction, an additional cycle of 80 mg/m2 on days 1 to 4 (in combination with mitoxantrone and cytarabine) as consolidation was administered (Ref) or 100 mg/m2 on days 1 to 5 (in combination with mitoxantrone); if complete remission occurred following induction, an additional cycle of 75 mg/m2 on days 1 to 5 (in combination with mitoxantrone and cytarabine) as consolidation was administered (Ref).
Adrenocortical carcinoma, advanced (off-label use):
IV: 100 mg/m2 on days 2, 3, and 4 every 4 weeks (in combination with doxorubicin, cisplatin, and mitotane) (Ref) or 100 mg/m2 on days 5, 6, and 7 every 4 weeks (in combination with doxorubicin, cisplatin, and mitotane) until disease progression or unacceptable toxicity up to a maximum of 6 cycles (Ref).
AIDS-related Kaposi sarcoma (off-label use; based on limited data):
Oral: 20 mg/m2 every 8 hours for 7 consecutive days every 21 days until persistent toxicity or a therapy delay beyond day 28 occurs (Ref) or 50 mg (flat dose) once daily for 7 consecutive days every 14 days; after 2 cycles, in patients without a response (complete or partial), may escalate the dose to 100 mg (flat dose) once daily for 7 consecutive days every 14 days (Ref).
Brain metastases, due to breast or non–small cell lung cancers (off-label use):
IV: 100 mg/m2 on days 1, 3, and 5 (or on days 4, 6, and 8) every 3 weeks (in combination with cisplatin) for up to 6 cycles in the absence of disease progression or unacceptable toxicity (Ref).
Intrathecal/Intraventricular (off- label route; based on limited data): 1 mg via Ommaya reservoir once weekly until disease progression or unacceptable toxicity (Ref) or 0.5 mg via Ommaya reservoir once daily for 5 consecutive days per week every other week for a total of 8 weeks (20 total doses), followed by maintenance intrathecal therapy of 0.5 mg via Ommaya reservoir once daily for 5 consecutive days every 4 weeks; continue until disease progression (Ref) or 0.5 mg via Ommaya or Rickham reservoir once daily for 5 consecutive days every 2 to 5 weeks (Ref). Refer to articles for further information. Note: Preservative-free etoposide formulations should be utilized.
Breast cancer, metastatic (off-label use):
Oral: 50 mg/m2 once daily for 21 days of a 28-day cycle; continue until disease progression or unacceptable toxicity (Ref).
Gestational trophoblastic neoplasia, high risk (off-label use):
EMA-CO regimen: IV: 100 mg/m2 on days 1 and 2 every 2 weeks (in combination with methotrexate, leucovorin, dactinomycin, cyclophosphamide, and vincristine); continue for at least 2 treatment cycles after a normal hCG level (Ref).
EMA-EP regimen: IV: 100 mg/m2 on days 1, 2, and 8 every 2 weeks (in combination with methotrexate, leucovorin, dactinomycin, and cisplatin) for 2 to 4 treatment cycles after a normal hCG level (Ref).
EP-EMA regimen: EP: IV: 150 mg/m2 on day 1 (followed by cisplatin) alternating weekly with EMA: 100 mg/m2 on day 1 (in combination with methotrexate, leucovorin, and dactinomycin) (Ref).
BEP regimen (for refractory disease ): IV: 100 mg/m2 on days 1 to 4 every 3 weeks (in combination with bleomycin, cisplatin, and WBC growth factor support) for at least 2 treatment cycles after a normal hCG level (Ref).
ICE regimen (for refractory disease; based on limited data): IV: 75 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with ifosfamide, mesna, and carboplatin) for at least 2 treatment cycles after a normal hCG level (Ref).
TP/TE regimen (for refractory disease): IV: 150 mg/m2 on day 15 of a 28-day cycle (TE; in combination with paclitaxel) alternating every 2 weeks with TP (paclitaxel and cisplatin); continue until hCG level is normal for at least 8 weeks, or until treatment resistance (plateaued or rising hCG) or unacceptable toxicity (Ref).
Low-dose EP induction regimen (consider prior to EMA/CO in patients with high tumor burden): IV: 100 mg/m2 on days 1 and 2 every week (in combination with cisplatin) for 1 to 2 cycles, followed by the EMA-CO regimen until hCG levels normalize and then for a further 6 to 8 weeks; refer to protocol for further information (Ref).
Hematopoietic cell transplant conditioning regimen (off-label use):
IV: 100 mg/m2 or 200 mg/m2 once daily for 4 days on days −5, −4, −3, and −2 prior to autologous transplant (in combination with carmustine, cytarabine, and melphalan [BEAM regimen]) (Ref) or 60 mg/kg as a single dose on day −4 prior to autologous transplant (in combination with cyclophosphamide and total body irradiation) (Ref) or 60 mg/kg as a single dose on day −3 prior to allogeneic transplant (in combination with total body irradiation) (Ref).
Hemophagocytic lymphohistiocytosis (off-label use):
HLH-94 protocol:
Initial therapy: IV: 150 mg/m2 twice weekly for 2 weeks, then 150 mg/m2 once weekly for 6 weeks (in combination with dexamethasone) (Ref).
Continuation therapy (depending on clinical factors; refer to protocol for details): IV: 150 mg/m2 once every 2 weeks (in combination with dexamethasone pulses, cyclosporine, and intrathecal methotrexate) until hematopoietic cell transplant (Ref).
Note: Consider reducing the etoposide frequency from twice weekly to once weekly and/or a dose reduction from 150 mg/m2/dose to 50 to 100 mg/m2/dose in adults with comorbidities or organ dysfunction; in patients with hemophagocytic lymphohistiocytosis without malignancy, a maximum cumulative etoposide dose of 2 to 3 g/m2 should not be exceeded (Ref).
Hodgkin lymphoma (off-label use):
BEACOPP (escalated) regimen: IV: 200 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for 4 to 8 cycles (Ref).
Stanford V regimen: IV: 60 mg/m2 on days 1 and 2 of weeks 3, 7, and 11 of a 12-week cycle (in combination with mechlorethamine, vinblastine, vincristine, bleomycin, doxorubicin, and prednisone) (Ref).
Merkel cell carcinoma, high risk (off-label use):
IV: 80 mg/m2 on days 1 to 3 (in combination with carboplatin) during weeks 1 and 4 of concurrent synchronous radiation therapy and then 80 mg/m2 on days 1 to 3 during weeks 7 and 10 (in combination with carboplatin) (or every 28 days if blood counts not recovered) for a total of 4 cycles (Ref).
Multiple myeloma (off-label use):
DT-PACE regimen: IV: 40 mg/m2/day administered as a continuous infusion on days 1 to 4 of each cycle; repeat every 4 to 6 weeks (in combination with dexamethasone, thalidomide, cisplatin, doxorubicin, and cyclophosphamide) (Ref).
VDT-PACE regimen: IV: 40 mg/m2/day administered as a continuous infusion on days 1 to 4 of each cycle; repeat every 4 to 6 weeks (in combination with bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, and cyclophosphamide) (Ref).
Neuroendocrine tumors, metastatic carcinoma (off-label use):
IV: 100 mg/m2 on days 1, 2, and 3 every 4 weeks (in combination with cisplatin; refer to protocol for infusion information) until disease progression or unacceptable toxicity (Ref) or 130 mg/m2 as a continuous infusion on days 1, 2, and 3 every 4 weeks (in combination with cisplatin) until disease progression or unacceptable toxicity (Ref) or 100 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with cisplatin) for up to 6 cycles (Ref).
Non-Hodgkin lymphomas (off-label use):
Diffuse large B-cell lymphoma:
Dose-adjusted EPOCH-R regimen: IV: Initial: 50 mg/m2/day continuous infusion for 4 days (over 96 hours) (total 200 mg/m2/cycle) of a 21-day treatment cycle (in combination with prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) for 6 to 8 cycles; dose-adjusted for subsequent cycles based on neutrophil and platelet counts during nadir (Ref).
R-CEOP regimen: IV, Oral: 50 mg/m2 IV on day 1, followed by 100 mg/m2 orally on days 2 and 3 of a 21-day treatment cycle for 3 to 6 cycles (in combination with rituximab, cyclophosphamide, vincristine, and prednisone) (Ref).
R-ICE regimen: IV: 100 mg/m2 on days 3, 4, and 5 (in combination with rituximab, ifosfamide, mesna, and carboplatin) every 2 weeks for 3 cycles (Ref).
Peripheral T-cell lymphoma:
CHOEP regimen: IV: 100 mg/m2 on days 1, 2, and 3 of a 21-day treatment cycle (in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone) for 6 to 8 cycles (Ref).
Primary mediastinal B-cell lymphoma:
DA-EPOCH-R regimen: Initial: IV: 50 mg/m2/day as a continuous infusion on days 1 to 4 (over 96 hours) dose-adjusted for subsequent cycles based on neutrophil and platelet counts during nadir (in combination with vincristine, prednisone, cyclophosphamide, doxorubicin, rituximab, and filgrastim); repeat cycle every 3 weeks for a total of 6 to 8 cycles (Ref).
Other non-Hodgkin lymphoma regimens:
CEPP(B) regimen: Initial: IV: 70 mg/m2 on days 1, 2, and 3; may increase dose with subsequent cycles (refer to protocol for details) every 28 days (in combination with cyclophosphamide, procarbazine, prednisone, ± bleomycin) (Ref).
ESHAP regimen: IV: 40 mg/m2 on days 1 to 4 (in combination with methylprednisolone, cisplatin, and cytarabine) every 3 to 4 weeks for 6 to 8 cycles (Ref).
PEP-C regimen: Oral: 50 mg (flat dose) once daily after dinner (length of induction cycle depends on blood counts; frequency may vary based on tolerance in maintenance cycle; in combination with prednisone, procarbazine, and cyclophosphamide) (Ref).
Non–small cell lung cancer (off-label use):
Stages I, II, or III disease : IV: 100 mg/m2 days 1, 2, and 3 every 3 weeks for 4 cycles or every 4 weeks for 3 to 4 cycles (in combination with cisplatin) (Ref).
Stage III disease: IV: 50 mg/m2 days 1 to 5 and days 29 to 33 (in combination with cisplatin and radiation therapy) (Ref).
Ovarian cancer, epithelial, refractory (off-label use):
Oral: 50 mg/m2 once daily for 21 days every 4 weeks until disease progression or unacceptable toxicity (Ref).
Ovarian germ cell tumors (off-label use):
BEP regimen: IV: 100 mg/m2 on days 1 to 5 every 21 days (in combination with bleomycin and cisplatin) for 3 cycles (Ref).
EP regimen: IV: 100 mg/m2 on days 1 to 5 every 21 days (in combination with cisplatin) for 4 cycles (Ref); while the BEP regimen is preferred in the treatment of ovarian germ cell tumors, EP may be considered if pulmonary toxicity is a concern. Note: Use of this regimen in ovarian germ cell tumors is extrapolated from data in the management of testicular germ cell tumors.
Carboplatin/etoposide regimen: IV: 120 mg/m2 days 1, 2, and 3 every 4 weeks (in combination with carboplatin) for 3 cycles (Ref).
Prostate cancer, metastatic, castration resistant (off-label use):
IV, Oral: 120 mg/m2 IV on days 1, 2, and 3 every 3 weeks (in combination with cisplatin, as second-line treatment following first-line treatment with carboplatin and docetaxel) for at least 4 cycles (Ref) or 80 mg/m2 IV on day 1, followed by 80 mg/m2 orally on days 2 and 3 (in combination with carboplatin) every 3 weeks until disease progression or unacceptable toxicity (Ref).
Sarcomas, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, refractory (off-label use):
Adults <22 years of age: IV: 100 mg/m2/day on days 1 to 5 every 3 weeks (in combination with ifosfamide, mesna, and carboplatin) (Ref).
Small cell lung cancer (combination chemotherapy):
Limited-stage disease (off-label dosing/combinations): IV: 120 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with cisplatin and concurrent radiation) for 4 courses (Ref) or 100 mg/m2 on days 1, 2, and 3 every 4 weeks (in combination with cisplatin and concurrent radiation) for 4 cycles (Ref) or 100 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with cisplatin and sequential radiation) for 4 cycles (Ref) or 100 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with carboplatin and radiation) up to a maximum of 6 cycles (Ref) or 100 mg/m2 IV on day 1 (in combination with cisplatin and concurrent radiation), followed by 200 mg/m2 orally on days 2 through 4 every 3 weeks for a maximum of 5 courses (Ref) or 100 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in combination with cisplatin) for 6 cycles (Ref). According to American Society of Clinical Oncology (ASCO) guidelines, platinum-based therapy (cisplatin or carboplatin) in combination with either etoposide or irinotecan for 4 cycles is recommended over other regimens for limited-stage disease (Ref).
Extensive-stage disease (off-label dosing/combinations): IV: 100 mg/m2 IV on days 1, 2, and 3 every 3 weeks (in combination with carboplatin and atezolizumab) for 4 induction cycles, followed by atezolizumab maintenance therapy (Ref) or 100 mg/m2 IV on days 1, 2, and 3 every 3 weeks (in combination with cisplatin) for 4 cycles (Ref) or 100 mg/m2 IV on day 1 (in combination with cisplatin and concurrent radiation), followed by 200 mg/m2 orally on days 2 through 4 every 3 weeks for a maximum of 5 courses (Ref) or 80 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with cisplatin) up to 8 cycles (Ref) or 100 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with carboplatin) up to a maximum of 6 cycles (Ref) or 100 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in combination with cisplatin) for 6 cycles (Ref). According to ASCO guidelines, platinum-based therapy (cisplatin or carboplatin) in combination with either etoposide or irinotecan for 4 to 6 cycles is recommended over other regimens for extensive-stage disease (Ref).
IV to oral conversion: Due to poor bioavailability, oral doses should be twice the IV dose (and rounded to the nearest 50 mg) according to the manufacturer.
Soft tissue sarcoma (off-label use):
EIA regimen: IV: 125 mg/m2 on days 1 and 4 (in combination with ifosfamide, doxorubicin, and regional hyperthermia) every 3 weeks until progression or unacceptable toxicity (Ref).
Testicular cancer, combination chemotherapy:
Testicular germ cell tumor, metastatic, good risk: IV: 100 mg/m2 on days 1 to 5 every 3 weeks (in combination with cisplatin) for 4 cycles (Ref).
Testicular germ cell tumor, metastatic, intermediate or poor risk: IV: 100 mg/m2 on days 1 to 5 every 3 weeks (in combination with bleomycin and cisplatin) for 4 cycles or 75 mg/m2 on days 1 to 5 every 3 weeks (in combination with cisplatin, ifosfamide, and mesna) for 4 cycles (Ref).
Testicular germ cell tumor, metastatic, high-dose regimens: IV: 750 mg/m2/day administered 5, 4, and 3 days before peripheral blood stem cell infusion (in combination with carboplatin); repeat for a second cycle after recovery of granulocyte and platelet counts (Ref) or 400 mg/m2/day (beginning on cycle 3) on days 1, 2, and 3, with peripheral blood stem cell support, administered at 14- to 21-day intervals (in combination with carboplatin) for 3 cycles (Ref).
Thymoma or thymic carcinoma, locally advanced, unresectable (off-label use):
Definitive chemoradiotherapy:
Note: There are no randomized clinical trials to provide specific guidance; dosing is derived from locally advanced non–small cell lung cancer clinical trials.
Cisplatin and etoposide (PE) regimen: IV: 50 mg/m2 on days 1 to 5 of a 4-week treatment cycle (in combination with cisplatin and concurrent radiotherapy) for 2 cycles (Ref).
Thymoma or thymic carcinoma, advanced or metastatic (initial therapy) (off-label use):
Single-agent therapy: Oral: 25 mg three times daily for 3 weeks of a 4-week treatment cycle (3 weeks on, 1 week off) until disease progression or unacceptable toxicity (Ref).
PE regimen: IV: 120 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with cisplatin) for up to 8 cycles (Ref).
VIP regimen: IV: 75 mg/m2 on days 1 to 4 (in combination with ifosfamide and cisplatin) every 3 weeks for up to 4 cycles or until disease progression or unacceptable toxicity (Ref).
Unknown primary adenocarcinoma (off-label use):
Oral: 50 mg once daily on days 1, 3, 5, 7, and 9 alternating with 100 mg once daily on days 2, 4, 6, 8, and 10 every 3 weeks (in combination with paclitaxel and carboplatin) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Empiric dose adjustments of etoposide are based on correlation between kidney function with AUC and risk of adverse hematologic events (Ref). Physiologic elimination of etoposide is complex with extensive interpatient variability (Ref); kidney function is one consideration for dosage in context of additional factors influencing drug disposition and toxicity (patient age, blood albumin, UDP-glucuronosyltransferase 1A1 activity, liver function, concurrent medications) (Ref).
Altered kidney function: IV, oral:
CrCl >50 mL/minute: No dosage adjustment necessary (Ref).
CrCl 15 to 50 mL/minute: Administer 75% of the usual indication-specific dose (Ref).
CrCl <15 mL/minute: Administer 50% of the usual indication-specific dose (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV, oral: No dosage adjustment necessary. Clinical data is insufficient to support empiric etoposide dosage adjustment for ARC (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable (Ref):
IV, Oral: Initial: Administer 50% of the usual indication-specific dose; can administer independently of hemodialysis schedule (Ref). Note: Two case series suggest that etoposide pharmacokinetics are relatively unaltered in hemodialysis patients. Given the extensive interpatient variability in etoposide pharmacokinetics, doses may be cautiously increased based on intent of therapy (curative versus noncurative), tolerability, and response (Ref).
Peritoneal dialysis: Not significantly dialyzable (Ref):
IV, oral: Initial: Administer 50% of the usual indication-specific dose (Ref). Note: Given the extensive interpatient variability in etoposide pharmacokinetics, doses may be cautiously titrated based on intent of therapy (curative versus noncurative), tolerability, and response (Ref).
CRRT: Note: Close monitoring of response and adverse reactions (eg, hematologic toxicity, mucositis) due to drug accumulation is important.
IV, oral: Dose as for CrCl <15 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Note: Close monitoring of response and adverse reactions (eg, hematologic toxicity, mucositis) due to drug accumulation is important.
IV, oral: Dose as for CrCl <15 mL/minute (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
The following adjustments have also been recommended:
Liver dysfunction may reduce the metabolism and increase the toxicity of etoposide. Normal doses of IV etoposide should be given to patients with liver dysfunction (dose reductions may result in subtherapeutic concentrations); however, use caution with concomitant liver dysfunction (severe) and renal dysfunction as the decreased metabolic clearance cannot be compensated by increased renal clearance (Ref).
Bilirubin 1.5 to 3 mg/dL or AST >3 times ULN: Administer 50% of dose (Ref).
Bilirubin 1.5 to 3 mg/dL or AST >180 units/L: Administer 50% of dose (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
The following may occur with higher doses used in stem cell transplantation: Alopecia, ethanol intoxication, hepatitis, hypotension (infusion-related), metabolic acidosis, mucositis, nausea and vomiting (severe), secondary malignancy, skin lesions (resembling Stevens-Johnson syndrome).
>10%:
Dermatologic: Alopecia (8% to 66%)
Gastrointestinal: Nausea and vomiting (31% to 43%), anorexia (10% to 13%), diarrhea (1% to 13%)
Hematologic & oncologic: Leukopenia (60% to 91%; grade 4: 3% to 17%; nadir: 7 to 14 days; recovery: by day 20), thrombocytopenia (22% to 41%; grades 3/4: 1% to 20%; nadir: 9 to 16 days; recovery: by day 20), anemia (≤33%)
1% to 10%:
Cardiovascular: Hypotension (1% to 2%; due to rapid infusion)
Central nervous system: Peripheral neuropathy (1% to 2%)
Gastrointestinal: Stomatitis (1% to 6%), abdominal pain (≤2%)
Hepatic: Hepatotoxicity (≤3%)
Hypersensitivity: Anaphylactoid reaction (intravenous: 1% to 2%; oral capsules: <1%; including bronchospasm, chills, dyspnea, fever, tachycardia)
<1%, postmarketing, and/or case reports: Amenorrhea, apnea (hypersensitivity-associated), back pain, constipation, cortical blindness (transient), cough, cyanosis, diaphoresis, drowsiness, dysphagia, erythema, esophagitis, extravasation (induration/necrosis), facial swelling, fatigue, fever, hyperpigmentation, hypersensitivity reaction, interstitial pneumonitis, ischemic heart disease, laryngospasm, maculopapular rash, malaise, metabolic acidosis, mucositis, myocardial infarction, optic neuritis, ovarian failure, pruritic erythematous rash, pruritus, pulmonary fibrosis, radiation-recall phenomenon (dermatitis), reversible posterior leukoencephalopathy syndrome (RPLS), seizure, skin rash, Stevens-Johnson syndrome, tongue edema, toxic epidermal necrolysis, toxic megacolon, urticaria, vasospasm, weakness
Hypersensitivity to etoposide or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Severe leukopenia or thrombocytopenia; severe hepatic impairment; severe renal impairment.
Concerns related to adverse effects:
• Bone marrow suppression: Severe myelosuppression with resulting infection or bleeding may occur. Myelosuppression is dose related and dose limiting. Granulocyte and platelet nadirs typically occur 7 to 14 days or 9 to 16 days, respectively, after administration; hematologic recovery usually occurs by day 20.
• Extravasation: Etoposide IV is an irritant (Pérez Fidalgo 2012); tissue irritation and inflammation have occurred following extravasation.
• Hypersensitivity: May cause anaphylactic-like reactions manifested by chills, fever, tachycardia, bronchospasm, dyspnea, and hypotension. In addition, facial/tongue swelling, coughing, chest tightness, cyanosis, laryngospasm, diaphoresis, hypertension, back pain, loss of consciousness, and flushing have also been reported less commonly. Incidence is primarily associated with IV administration (up to 2%) compared to oral administration (<1%). High drug concentration and rate of infusion, as well as presence of polysorbate 80 and benzyl alcohol in the etoposide IV formulation, have been suggested as contributing factors to the development of hypersensitivity reactions. Etoposide IV formulations may contain polysorbate 80 and/or benzyl alcohol, while etoposide phosphate (the water-soluble prodrug of etoposide) IV formulation does not contain either vehicle. Case reports have suggested that etoposide phosphate has been used successfully in patients with previous hypersensitivity reactions to etoposide (Collier 2008; Siderov 2002).
• Hypotension: Hypotension may occur due to rapid administration.
• Secondary malignancies: Secondary acute leukemias have been reported with etoposide, either as monotherapy or in combination with other chemotherapy agents.
Disease-related concerns:
• Hypoalbuminemia: Use with caution in patients with low serum albumin; may increase risk for toxicities.
Special populations:
• Older adult: Patients ≥65 years of age may be more likely to develop severe myelosuppression and/or GI effects.
• Pediatrics: The use of concentrations higher than recommended were associated with higher rates of anaphylactic-like reactions in children.
Dosage form specific issues:
• Alcohol: Injectable formulation contains alcohol (~30% to 33% v/v); may contribute to adverse reactions, especially with higher etoposide doses.
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 50 mg
Solution, Intravenous:
Toposar: 100 mg/5 mL (5 mL [DSC]); 500 mg/25 mL (25 mL [DSC]); 1 g/50 mL (50 mL [DSC]) [contains alcohol, usp, polyethylene glycol 300 (peg-6), polysorbate 80]
Generic: 100 mg/5 mL (5 mL); 500 mg/25 mL (25 mL); 1 g/50 mL (50 mL)
Yes
Capsules (Etoposide Oral)
50 mg (per each): $100.44
Solution (Etoposide Intravenous)
1 gm/50 mL (per mL): $1.82 - $2.99
100 mg/5 mL (per mL): $1.20 - $2.99
500 mg/25 mL (per mL): $1.82 - $2.99
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
VePesid: 50 mg [contains ethylparaben, propylparaben]
Solution, Intravenous:
Generic: 20 mg/mL (5 mL, 10 mL, 20 mL, 25 mL, 50 mL)
10 mg/mL oral solution:
Dilute etoposide for injection 1:1 with normal saline to a concentration of 10 mg/mL. This solution is stable in plastic oral syringes for 22 days at room temperature (McLeod 1992). Prior to oral administration, further mix with fruit juice (orange or apple NOT grapefruit juice) or lemonade to a concentration of <0.4 mg/mL; once mixed with fruit juice, use within 3 hours (Lam 2011).
Note: Etoposide is associated with a low emetic risk (intravenous) and moderate emetic risk (oral); antiemetics may be recommended to prevent nausea and vomiting (Ref).
Oral: In adults, doses ≤200 mg/day should be given as a single daily dose; doses >200 mg should be given in 2 divided doses. If necessary, the injection may be used for oral administration either as an extemporaneous preparation or by mixing dose with orange juice, apple juice, or lemonade at a final concentration not to exceed 0.4 mg/mL (to improve palatability) (Ref). Based on a small pharmacokinetic study, food does not appear to significantly interfere with the bioavailability of a 100 mg etoposide dose (oral capsules); therefore, etoposide capsules may be administered in a fed or fasted state (with or without food) (Ref).
Parenteral:
IV: For IV infusion only; do not administer by rapid IV injection or by intrathecal, intraperitoneal, or intrapleural routes due to possible severe toxicity. Etoposide injection contains polysorbate 80 which may cause leaching of diethylhexyl phthalate (DEHP), a plasticizer contained in polyvinyl chloride (PVC) tubing (Ref). Administration through non-PVC (low sorbing) tubing will minimize patient exposure to DEHP (Ref). Etoposide is an irritant; tissue irritation and inflammation have occurred following extravasation; avoid extravasation.
Administer by continuous IV infusion or IV intermittent infusion over at least 60 minutes at a rate not to exceed 100 mg/m2/hour (or 3.3 mg/kg/hour) to minimize the risk of hypotension. Due to risk for precipitation, a 0.22-micron inline filter may be used. Hematopoietic stem cell transplantation conditioning regimens have infused etoposide through a central venous catheter over 4 to 8 hours (Ref). Higher than recommended concentrations of etoposide infusions may crack hard plastic in chemo venting pins and infusion lines; inspect infusion solution for particulate matter and plastic devices for cracks and leaks.
Intraventricular: In pediatric patients, doses were injected over 2 minutes (Ref).
Oral: Doses ≤200 mg/day may be administered as a single once daily dose; doses >200 mg should be given in 2 divided doses. Based on a small pharmacokinetic study, food does not appear to significantly interfere with the bioavailability of a 100 mg etoposide dose (oral capsules); therefore, etoposide capsules may be administered in a fed or fasted state (with or without food) (Ref). If necessary, the injection may be used to prepare an extemporaneous oral solution for oral administration (see Extemporaneously Prepared).
IV: Administer standard doses over at least 30 to 60 minutes to minimize the risk of hypotension. Higher (off-label) doses used in transplantation may be infused over longer time periods depending on the protocol (refer to protocol for infusion duration). Etoposide injection contains polysorbate 80 which may cause leaching of DEHP, a plasticizer contained in PVC tubing (Ref). Administration through non-PVC (low sorbing) tubing will minimize patient exposure to DEHP (Ref). Etoposide is an irritant; tissue irritation and inflammation have occurred following extravasation; avoid extravasation.
Etoposide should be diluted to a concentration of 0.2 to 0.4 mg/mL; precipitation may occur with concentrations >0.4 mg/mL. For large doses, where dilution to ≤0.4 mg/mL is not feasible, consideration should be given to slow infusion of the undiluted drug through a running normal saline, dextrose or saline/dextrose infusion or use of etoposide phosphate. Higher than recommended concentrations of etoposide infusions (including undiluted etoposide) may crack hard plastic in chemo transfer devices or venting pins and infusion lines; inspect infusion solution for particulate matter and plastic devices for cracks and leaks.
Intrathecal/Intraventricular (off-label route): In clinical reports, etoposide was administered over 2 minutes via an Ommaya or Rickham reservoir. Prior to administration, 5 to 6 mL of CSF fluid was drained for discarding (Ref). Corticosteroids were administered as prophylaxis for chemical arachnoiditis in some reports (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Capsules:
US labeling: Store oral capsules at 2°C to 8°C (36°F to 46°F); do not freeze. Dispense in a light-resistant container.
Canadian labeling: Store at room temperature.
Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); do not freeze. According to the manufacturer's labeling, stability for solutions diluted for infusion in D5W or NS (in glass or plastic containers) varies based on concentration; 0.2 mg/mL solutions are stable for 96 hours at room temperature and 0.4 mg/mL solutions are stable for 24 hours at room temperature (precipitation may occur at concentrations above 0.4 mg/mL). Follow USP 797 recommendations for beyond use dates based on the level of risk for preparation.
Etoposide injection contains polysorbate 80 which may cause leaching of DEHP, a plasticizer contained in PVC bags and tubing. Higher concentrations and longer storage time after preparation in PVC bags may increase DEHP leaching. Preparation in glass or polyolefin containers will minimize patient exposure to DEHP (de Lemos 2005; Demoré 2002). When undiluted etoposide injection is stored in acrylic or ABS (acrylonitrile, butadiene and styrene) plastic containers, the containers may crack and leak.
Treatment of refractory testicular tumors (Parenteral: FDA approved in adults) and small cell lung cancer (Oral and parenteral: FDA approved in adults); has also been used for treatment of lymphoma, Hodgkin disease, leukemias (acute lymphoblastic leukemia and acute myeloid leukemia), neuroblastoma, Ewing sarcoma, retinoblastoma, Wilms tumor, CNS tumors, and hemophagocytic lymphohistiocytosis (HLH), and as part of a conditioning regimen prior to hematopoietic stem cell transplantation (HSCT).
Etoposide may be confused with teniposide
Etoposide may be confused with etoposide phosphate (a prodrug of etoposide which is rapidly converted in the plasma to etoposide)
VePesid may be confused with Versed
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral; epidural and intrathecal medications) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP1A2 (Minor), CYP2E1 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), P-glycoprotein (Major with inhibitors), P-glycoprotein (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Atovaquone: May increase serum concentration of Etoposide. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
CISplatin: May increase serum concentration of Etoposide. Risk C: Monitor
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CycloSPORINE (Systemic): May decrease metabolism of Etoposide. Management: Consider reducing the dose of etoposide by 50% if the patient is receiving, or has recently received, cyclosporine. Monitor for increased toxic effects of etoposide if cyclosporine is initiated, the dose is increased, or it has been recently discontinued. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Etoposide. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Grapefruit Juice: May decrease serum concentration of Etoposide. Risk C: Monitor
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lonafarnib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Etoposide. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
Vitamin K Antagonists: Etoposide may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
In patients who could become pregnant, product labeling for etoposide phosphate notes that it may cause amenorrhea, infertility, or premature menopause; effective contraception should be used during therapy and for at least 6 months after the last dose. In males, azoospermia, oligospermia, or permanent loss of fertility may occur. In addition, spermatozoa and testicular tissue may be damaged. Patients with partners who could become pregnant should use condoms during therapy and for at least 4 months after the last dose.
Adverse events were observed in animal reproduction studies. Fetal growth restriction and newborn myelosuppression have been observed following maternal use of regimens containing etoposide during pregnancy (NTP 2013; ESMO [Peccatori 2013]).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided during in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
CBC with differential and platelet count, hemoglobin, vital signs (blood pressure) during infusion, albumin, bilirubin, liver and renal function tests.
Etoposide has been shown to delay transit of cells through the S phase and arrest cells in late S or early G2 phase. The drug may inhibit mitochondrial transport at the NADH dehydrogenase level or inhibit uptake of nucleosides into HeLa cells. It is a topoisomerase II inhibitor and appears to cause DNA strand breaks. Etoposide does not inhibit microtubular assembly.
Absorption: Oral: Significant inter- and intrapatient variation
Distribution: Average Vd: Children: 10 L/m2; Adults: 7 to 17 L/m2; poor penetration across the blood-brain barrier; CSF concentrations <5% of plasma concentrations
Protein binding: 94% to 98%
Metabolism: Hepatic, via CYP3A4 and 3A5, to various metabolites; in addition, conversion of etoposide to the O-demethylated metabolites (catechol and quinine) via prostaglandin synthases or myeloperoxidase occurs, as well as glutathione and glucuronide conjugation via GSTT1/GSTP1 and UGT1A1 (Yang 2009)
Bioavailability: Oral: ~50% (range: 25% to 75%)
Half-life elimination: Terminal: IV: Normal renal/hepatic function: Children: 6 to 8 hours: Adults: 4 to 11 hours
Excretion:
Children: IV: Urine (~55% as unchanged drug) in 24 hours
Adults: IV: Urine (56%; 45% as unchanged drug) within 120 hours; feces (44%) within 120 hours
Altered kidney function: Total body clearance is reduced, AUC is increased, and Vd is lower.
