ENZALUTAMIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Androgen receptor inhibitor; binds to the androgen receptor and inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment.

What the body does with it

Metabolism	Primarily metabolized by CYP2C8 and CYP3A4; forms active metabolite N-desmethyl enzalutamide
Excretion	Primarily hepatic metabolism; ~70% of dose excreted in feces (as unchanged drug and metabolites), ~1% in urine as unchanged drug. Biliary excretion is a major route.
Half-life	Terminal elimination half-life is approximately 5.8 days (range 2.8–10.2 days) after steady state; supports once-daily dosing.
Protein binding	97–98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 110 L (1.1 L/kg for a 70 kg patient); indicates extensive extravascular distribution.
Bioavailability	Oral bioavailability is not published; absorption is at least moderate based on systemic exposure. Food does not significantly affect absorption.
Onset of Action	Oral: Clinical effect (e.g., PSA decline) typically observed within 4–12 weeks; time to maximal androgen receptor inhibition not precisely defined.
Duration of Action	Not well-defined; continuous therapy recommended until disease progression or unacceptable toxicity. Sustained receptor blockade persists with regular dosing.

Classification & Brands

Dosing & administration

160 mg orally once daily

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min). Insufficient data for severe renal impairment (eGFR <30 mL/min) or end-stage renal disease.
Liver impairment	No dose adjustment for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B): reduce dose to 80 mg once daily. Not recommended for severe (Child-Pugh C).
Pediatric use	Not approved for use in pediatric patients; safety and efficacy not established.
Geriatric use	No specific dose adjustment required; elderly patients may be more susceptible to adverse effects such as falls, fractures, and hypertension. Monitor closely.

Use during pregnancy

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

Clinical note

Strong CYP2C8 inhibitors may increase levels and inducers may decrease levels Can cause seizures and posterior reversible encephalopathy syndrome (PRES).

Breastfeeding	No human data available. Enzalutamide and its active metabolite are likely excreted into human milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for 1 month after the last dose. M/P ratio is unknown.
Teratogenic Risk	Enzalutamide is contraindicated in pregnancy. Based on its mechanism of action (androgen receptor inhibitor), there is a high risk of fetal harm, particularly male pseudohermaphroditism and impaired reproductive development. Use should be avoided in all trimesters. Women of childbearing potential must use effective contraception during treatment and for 1 month after the last dose.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Hot flashes
Serious Effects

Absolute Contraindications

["Pregnancy","Concomitant use with strong CYP2C8 inhibitors or inducers","Concomitant use with strong CYP3A4 inducers"]

Clinical Precautions

Precautions

["Seizure risk","Posterior reversible encephalopathy syndrome (PRES)","Hypersensitivity reactions including angioedema","Increased risk of falls and fractures","Embryo-fetal toxicity"]

Clinical Tips & Counseling

Drug interactions

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