ENZALUTAMIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Androgen receptor inhibitor; binds to the androgen receptor and inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment.
| 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. |
| Molecular Weight | 464.44 |
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. |
| 1st trimester | Enzalutamide is an androgen receptor inhibitor. Based on animal studies and its mechanism of action, there is a risk of fetal harm, including potential feminization of male fetuses and other developmental abnormalities. Use is contraindicated in pregnancy. Adequate contraception is required for men with female partners of reproductive potential. |
| 2nd trimester | Same as trimester 1. Enzalutamide should not be used during pregnancy due to potential androgen receptor antagonism effects on fetal development. |
| 3rd trimester | Same as trimester 1. No change in risk assessment across trimesters. |
Clinical note
Strong CYP2C8 inhibitors may increase levels and inducers may decrease levels Can cause seizures and posterior reversible encephalopathy syndrome (PRES).
| Placental transfer | Enzalutamide is expected to cross the placenta due to its molecular weight (<500 Da) and lipophilicity. Animal studies confirm placental transfer and fetal exposure. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Common Effects | Hot flashes |
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraception
| Precautions | Seizure risk, Posterior reversible encephalopathy syndrome (PRES), Hypersensitivity reactions including angioedema, Increased risk of falls and fractures, Embryo-fetal toxicity |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice as it may increase enzalutamide levels (minor interaction). Take with or without food. |
Loading safety data…
| Not indicated for use in breastfeeding women. Excretion into human milk is unknown, but due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 1 month after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Pregnancy testing is recommended before initiating enzalutamide in women of childbearing potential. Fetal monitoring includes ultrasound for genitourinary anomalies if inadvertent exposure occurs. Maternal monitoring includes blood pressure (risk of hypertension) and seizure assessment. |
| Fertility Effects | Enzalutamide may impair male fertility based on animal studies showing reduced sperm count and motility. In humans, reversible effects on spermatogenesis are possible. Females may experience amenorrhea or menstrual irregularities due to hormonal disruption. Contraception is required for both sexes during and up to 1 month after treatment. |
| Clinical Pearls | Monitor for seizure risk, especially in patients with predisposing factors; enzalutamide may cause hypertension, so check blood pressure regularly; it significantly induces CYP3A4, reducing efficacy of oral contraceptives and other CYP3A4 substrates; use with caution in patients with history of cardiovascular disease; discontinue 5 half-lives before starting another antiandrogen. |
| Patient Advice | Take the capsules whole, with or without food, at the same time each day. · Do not crush, chew, or open the capsules. · Report any signs of seizure (e.g., convulsions, loss of consciousness) to your doctor immediately. · Enzalutamide may raise your blood pressure; have it checked regularly. · Use effective non-hormonal contraception during treatment and for 3 months after stopping; hormonal contraceptives may not work. · This drug may cause fatigue, falls, and fractures; avoid activities requiring alertness until you know how it affects you. · Notify your doctor if you experience chest pain, shortness of breath, or leg swelling. · Seek immediate medical attention for symptoms of posterior reversible encephalopathy syndrome (PRES): headache, confusion, visual disturbances. |