ETOPOSIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Etoposide inhibits topoisomerase II, causing DNA strand breaks and preventing religation, leading to cell cycle arrest in the late S and G2 phases.

What the body does with it

Metabolism	Hepatic metabolism primarily via CYP3A4 and CYP2E1; also undergoes O-demethylation and glucuronidation.
Excretion	Renal excretion accounts for 35-50% of total clearance as unchanged drug; biliary/fecal excretion accounts for 15-20% as unchanged drug and metabolites. Dose adjustment recommended for creatinine clearance <50 mL/min.
Half-life	Terminal elimination half-life is 4-11 hours (mean 8 hours) in patients with normal renal function; prolonged to 20-40 hours in severe renal impairment.
Protein binding	94-97% bound to serum albumin; unbound fraction increases in hypoalbuminemia.
Volume of Distribution	Vd is 0.2-0.4 L/kg (7-17 L/m²); indicates extensive tissue distribution but limited CNS penetration.
Bioavailability	Oral bioavailability is 50% (range 25-75%) due to variable absorption and first-pass metabolism. Capsule and solution forms have comparable bioavailability.
Onset of Action	Intravenous: Onset of antineoplastic effect is 1-3 days; oral: 3-7 days.
Duration of Action	Duration of antineoplastic effect is 5-7 days after IV administration; 7-14 days after oral administration. Myelosuppression nadir occurs at 10-14 days.

Classification & Brands

Dosing & administration

IV: 100-120 mg/m2 daily for 3-5 days, repeated every 21-28 days; Oral: 100-400 mg/m2 daily for 3-5 days, repeated every 21-28 days.

Dosage form	INJECTABLE
Renal impairment	CrCl >50 mL/min: 100% dose; CrCl 15-50 mL/min: 75% dose; CrCl <15 mL/min: 50% dose.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	IV: 100-150 mg/m2 daily for 3-5 days, repeated every 21-28 days; Oral: 100-400 mg/m2 daily for 3-5 days, repeated every 21-28 days.
Geriatric use	Consider dose reduction based on renal function and performance status; monitor for myelosuppression and hypotension.

Use during pregnancy

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

Clinical note

Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and secondary leukemias.

Breastfeeding	Etoposide is excreted into human breast milk with a milk-to-plasma ratio of approximately 0.25. Due to potential for serious adverse effects in nursing infants (immunosuppression, carcinogenesis), breastfeeding is contraindicated during therapy and for at least 7 days after the last dose.
Teratogenic Risk	Etoposide is embryotoxic and fetotoxic in animal studies. In humans, first trimester exposure is associated with major congenital malformations (neural tube defects, skeletal anomalies) at rates >10%. Second and third trimester exposure increases risk of intrauterine growth restriction, low birth weight, and preterm delivery. Cytotoxic effects on rapidly dividing fetal tissues are dose-dependent.

Warnings & precautions

■ FDA Black Box Warning

Severe myelosuppression leading to infection or bleeding; secondary leukemias (especially with alkylating agents); anaphylactic reactions (hypotension, bronchospasm, urticaria) requiring immediate treatment; risk of embryo-fetal toxicity.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Severe hypersensitivity to etoposide or any component; severe hepatic impairment (Child-Pugh class C); concurrent use of yellow fever vaccine; breastfeeding (discontinue or avoid drug).

Clinical Precautions

Precautions

Bone marrow suppression (monitor CBC); hypotension (infusion rate-dependent); secondary acute myeloid leukemia; hypersensitivity reactions; renal impairment (dose adjustment); hepatic impairment; risk of tumor lysis syndrome; extravasation injury.

Clinical Tips & Counseling

Drug interactions

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