Etoposide !

A plant-derived drug that traps topoisomerase II on cut DNA. Used in testicular and small cell lung cancer; its main toxicity is bone-marrow suppression.

Updated 2026-11-01

Class: Topoisomerase inhibitors
Enzyme: DNA topoisomerase IIα
ATC code: L01CB01
WHO Model List of Essential Medicines

Also called: VP-16

DNA topoisomerase IIαEtoposide

The crystal shows the closely related human topoisomerase IIβ caught while cutting DNA, with etoposide wedged at the cleavage site.

Target in 3D: DNA topoisomerase IIα. PDB structure 3QX3 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Topoisomerase II cuts both DNA strands so another segment can pass through, then reseals the break. Etoposide binds the enzyme–DNA cleavage complex and stops the resealing step. The double-strand breaks accumulate, especially in cells in the S and G2 phases, and trigger apoptosis.

Topoisomerase II cuts both DNA strands
Etoposide locks the enzyme–DNA cleavage complex
Breaks are not resealed: double-strand breaks
Cells in S and G2 phases die

Pharmacokinetics

Absorption: Intravenous infusion or oral capsules; about half of an oral dose is absorbed, with wide variation.
Distribution: Highly bound to albumin: low albumin or high bilirubin raises the free fraction. Enters the cerebrospinal fluid poorly.
Elimination: Both by the kidneys (unchanged drug) and by metabolism and bile.
Half-life: Terminal half-life of about 4 to 11 hours.

Indications

Refractory testicular tumours, in combination. Testicular cancer →
Small cell lung cancer, first line in combination. Lung cancer →

Adverse effects

Common

Bone-marrow suppression (dose-limiting)
Nausea and vomiting
Reversible hair loss, sometimes total
Low blood pressure if infused too quickly

Contraindications

Previous hypersensitivity to etoposide or any component of the formulation

Key interactions

High-dose ciclosporin: Raises etoposide exposure and lowers its clearance.
Cisplatin: Associated with reduced etoposide clearance.
Other myelosuppressive therapy: Additive marrow suppression.

What is monitored

Platelets, haemoglobin and white cell count with differential at the start and before each cycle
Blood pressure during the infusion
Albumin, bilirubin and kidney function

Administration and safety

Given only as a slow intravenous infusion, never as a rapid push, because rapid injection can cause hypotension.
Emergency drugs for anaphylaxis are ready during the infusion.
Oral and intravenous products are dosed differently; the route on the order is checked.
Hazardous drug: prepared and given following hazardous-drug handling procedures (impervious gloves, no skin contact) and disposed of as cytotoxic waste.

Nursing care

Independent double check of drug, patient, route and cycle before giving it (high-alert medicine).
Blood pressure before and during the infusion; slow or stop the infusion and call if it falls.
Watch for chills, fever, wheeze or breathlessness during the infusion.
Blood count before each cycle; fever with neutropenia is treated as an emergency.
Teaching: report fever, chills, sore throat, bleeding or bruising at once.

Pregnancy and breastfeeding

Can cause fetal harm (teratogenic in animals); pregnancy is avoided during treatment.

Test yourself

Think of the answer, then tap the question to see it.

Which enzyme does etoposide inhibit, and at which step?

Topoisomerase II: it stabilises the enzyme–DNA cleavage complex and blocks resealing of the double-strand break.

Why is etoposide infused slowly rather than pushed?

Rapid intravenous injection can cause hypotension.

Which late, serious complication is linked to topoisomerase II inhibitors such as etoposide?

Secondary acute leukaemia.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - ETOPOSIDE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 70 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).

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Representative model, for educational purposes only.