VEPESID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VEPESID (VEPESID).

How it works

Topoisomerase II inhibitor; induces DNA strand breaks by stabilizing the topoisomerase II-DNA complex, inhibiting DNA relegation and causing cell cycle arrest at G2 phase.

What the body does with it

Metabolism	Hepatic metabolism via CYP3A4 and glucuronidation; also metabolized by catechol-O-methyltransferase (COMT).
Excretion	Renal (45-50% as unchanged drug), biliary/fecal (40-50% as metabolites and unchanged drug).
Half-life	Terminal elimination half-life: 4-11 hours (mean 8 hours). Clinically, no dose adjustment for mild renal impairment but caution in severe renal impairment (CrCl <10 mL/min) due to prolonged half-life.
Protein binding	95-97% bound to albumin.
Volume of Distribution	7-17 L/kg (mean 10 L/kg). Large Vd indicates extensive tissue distribution, crossing blood-brain barrier minimally.
Bioavailability	Oral: 50% (range 25-75%). IV: 100%.
Onset of Action	IV: 5-10 minutes (myelosuppression and antineoplastic effect); oral: 1-2 hours (clinical response may take days).
Duration of Action	Myelosuppression: 7-14 days (nadir); antineoplastic effect: variable, typically 2-3 weeks between cycles.

Classification & Brands

Dosing & administration

50-100 mg/m2 IV once daily on days 1-5, OR 100 mg/m2 IV once daily on days 1, 3, and 5, repeated every 3-4 weeks. Oral dose: 50-100 mg/m2 once daily for 14-21 days, repeated every 4 weeks.

Dosage form	INJECTABLE
Renal impairment	CrCl >50 mL/min: no adjustment. CrCl 15-50 mL/min: reduce dose by 25%. CrCl <15 mL/min: reduce dose by 50%, or consider alternate therapy.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: not recommended.
Pediatric use	100-150 mg/m2 IV once daily for 3 days, or 50-75 mg/m2 IV once daily for 5 days, repeated every 3-4 weeks. Oral: 50-100 mg/m2 once daily for 14-21 days.
Geriatric use	Start at lower end of dosing range (50 mg/m2 IV daily) due to increased risk of myelosuppression; monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VEPESID (VEPESID).

Breastfeeding

Not recommended during breastfeeding. Excreted into human milk; M/P ratio unknown. Potential for severe adverse reactions in nursing infants, including myelosuppression and carcinogenesis. Discontinue breastfeeding during treatment and for at least 30 days after last dose.

Teratogenic Risk

FDA Pregnancy Category D. Etoposide is embryotoxic and teratogenic in animal studies. First trimester: high risk of major malformations, including craniofacial defects, neural tube defects, and skeletal anomalies. Second and third trimesters: risk of intrauterine growth restriction, fetal myelosuppression, and neonatal pancytopenia. Use only if clearly needed and potential benefits outweigh risks.

Warnings & precautions

■ FDA Black Box Warning

Severe myelosuppression with fatal infections and bleeding; risk of secondary acute myeloid leukemia (especially with alkylating agents); hypersensitivity reactions including anaphylaxis; hypotension with rapid infusion.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe hypersensitivity to etoposide or any formulation component; severe hepatic impairment; pregnancy (category D).

Clinical Precautions

Precautions

Monitor complete blood counts due to myelosuppression; risk of secondary leukemia; hypersensitivity reactions (including anaphylaxis); hypotension with rapid administration; renal and hepatic impairment require dose adjustment; extravasation risk.

Clinical Tips & Counseling

Drug interactions

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VEPESID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VEPESID (VEPESID).

How it works

Topoisomerase II inhibitor; induces DNA strand breaks by stabilizing the topoisomerase II-DNA complex, inhibiting DNA relegation and causing cell cycle arrest at G2 phase.

What the body does with it

Metabolism	Hepatic metabolism via CYP3A4 and glucuronidation; also metabolized by catechol-O-methyltransferase (COMT).
Excretion	Renal (45-50% as unchanged drug), biliary/fecal (40-50% as metabolites and unchanged drug).
Half-life	Terminal elimination half-life: 4-11 hours (mean 8 hours). Clinically, no dose adjustment for mild renal impairment but caution in severe renal impairment (CrCl <10 mL/min) due to prolonged half-life.
Protein binding	95-97% bound to albumin.
Volume of Distribution	7-17 L/kg (mean 10 L/kg). Large Vd indicates extensive tissue distribution, crossing blood-brain barrier minimally.
Bioavailability	Oral: 50% (range 25-75%). IV: 100%.
Onset of Action	IV: 5-10 minutes (myelosuppression and antineoplastic effect); oral: 1-2 hours (clinical response may take days).
Duration of Action	Myelosuppression: 7-14 days (nadir); antineoplastic effect: variable, typically 2-3 weeks between cycles.

Classification & Brands

Dosing & administration

50-100 mg/m2 IV once daily on days 1-5, OR 100 mg/m2 IV once daily on days 1, 3, and 5, repeated every 3-4 weeks. Oral dose: 50-100 mg/m2 once daily for 14-21 days, repeated every 4 weeks.

Dosage form	INJECTABLE
Renal impairment	CrCl >50 mL/min: no adjustment. CrCl 15-50 mL/min: reduce dose by 25%. CrCl <15 mL/min: reduce dose by 50%, or consider alternate therapy.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: not recommended.
Pediatric use	100-150 mg/m2 IV once daily for 3 days, or 50-75 mg/m2 IV once daily for 5 days, repeated every 3-4 weeks. Oral: 50-100 mg/m2 once daily for 14-21 days.
Geriatric use	Start at lower end of dosing range (50 mg/m2 IV daily) due to increased risk of myelosuppression; monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VEPESID (VEPESID).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe hypersensitivity to etoposide or any formulation component; severe hepatic impairment; pregnancy (category D).