Enzalutamide (Xtandi) — Clinical FAQs

Question 1

What is Enzalutamide FDA-approved to treat?

Accepted Answer

Enzalutamide is FDA-approved for the following oncology indications: 1. Metastatic castration-resistant prostate cancer (mCRPC) — approved 2012 post-chemotherapy (AFFIRM trial) and 2014 chemotherapy-naive (PREVAIL trial) 2. Non-metastatic castration-resistant prostate cancer (nmCRPC) — approved 2018 (PROSPER trial) 3. Metastatic castration-sensitive prostate cancer (mCSPC) — approved 2023 (ARCHES trial) 4. Non-metastatic castration-sensitive prostate cancer (nmCSPC) — approved 2024 (EMBARK trial).

Question 2

How does Enzalutamide work (mechanism of action)?

Accepted Answer

Enzalutamide is a potent androgen receptor (AR) signaling inhibitor with three complementary mechanisms: it competitively binds the AR ligand-binding domain with 5- to 8-fold greater affinity than bicalutamide, preventing androgen binding; it inhibits AR nuclear translocation by blocking importin-mediated transport; and it prevents AR binding to androgen response elements on DNA, thereby abolishing transcriptional activation of AR target genes. Unlike first-generation antiandrogens, enzalutamide lacks agonist activity and does not promote AR nuclear translocation even in the setting of AR overexpression. This comprehensive blockade results in decreased prostate cancer cell proliferation and increased apoptosis.

Question 3

How is Enzalutamide administered?

Accepted Answer

Enzalutamide is administered Oral (PO). Enzalutamide 160 mg (four 40 mg capsules or one 160 mg tablet) PO once daily with or without food.

Question 4

What are the most common side effects of Enzalutamide?

Accepted Answer

The most commonly reported side effects of Enzalutamide (≥10% incidence) include: Fatigue/asthenia (51%), Hot flush (20%), Musculoskeletal pain (44%), Hypertension (14%), Nausea (11%) and others (12 total). Consult your oncologist for complete prescribing information.

Question 5

Does Enzalutamide have a black box warning?

Accepted Answer

Yes. Enzalutamide carries FDA black box warning(s) regarding: 1. Seizures: Seizures occurred in 0.5% of patients in clinical trials. Use with caution in patients with predisposing factors (prior seizure, CNS lesions, concurrent medications lowering seizure threshold). Permanently discontinue if seizure occurs.

Question 6

Is Enzalutamide safe during pregnancy?

Accepted Answer

Enzalutamide pregnancy safety: Contraindicated in pregnancy. Enzalutamide can cause fetal harm based on mechanism of action and animal studies. Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after last dose.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Enzalutamide — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms