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Xtandi

enzalutamide
Androgen Receptor Inhibitor Pfizer/Astellas FDA Approved 2012
Indications Dosing Forms Contraindications Warnings Adverse Reactions Pharmacology Clinical Studies Tumor Types
1. Indications and Usage

Castration-resistant prostate cancer (CRPC) — metastatic CRPC (both pre- and post-chemotherapy); Non-metastatic CRPC (nmCRPC) with rapidly rising PSA; Metastatic castration-sensitive prostate cancer (mCSPC).

2. Dosage and Administration

160 mg orally once daily (four 40 mg tablets/capsules)
Take with or without food
Swallow whole; do not chew, dissolve, or open capsules
Continue LHRH analogue concurrently or have had bilateral orchiectomy
Strong CYP2C8 inhibitors: Reduce to 80 mg once daily

3. Dosage Forms and Strengths

Tablets: 40 mg, 80 mg; Capsules: 40 mg

4. Contraindications

Pregnancy or women who may become pregnant (embryo-fetal toxicity).

5. Warnings and Precautions
  • Seizure: Occurred in 0.5% of patients. Avoid in patients with history of seizure, predisposing conditions, or concomitant medications that lower seizure threshold.
  • Posterior Reversible Encephalopathy Syndrome (PRES): Rare but reported.
  • Ischemic Heart Disease: Reported in 3.2% (fatal in 0.4%). Monitor cardiovascular status.
  • Falls and Fractures: Falls in 11%, fractures in 10%. Assess fracture/fall risk.
6. Adverse Reactions
Most Common Adverse Reactions

Fatigue/asthenia (51%), back pain (29%), hot flush (20%), constipation (17%), arthralgia (16%), diarrhea (17%), decreased appetite (18%), hypertension (14%), fall (11%), weight decreased (11%), headache (9%)

Fatigue/asthenia
51%
Back Pain
29%
Hot Flush
20%
Decreased Appetite
18%
Constipation
17%
Diarrhea
17%
Arthralgia
16%
Hypertension
14%
Fall
11%
Weight Decreased
11%

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

12. Clinical Pharmacology
Mechanism of Action

Enzalutamide is a potent androgen receptor (AR) signaling inhibitor that acts at three key steps: (1) competitively inhibits androgen binding to the AR, (2) inhibits nuclear translocation of activated AR, and (3) inhibits AR-mediated DNA binding and co-activator recruitment. Unlike first-generation anti-androgens (bicalutamide), enzalutamide has no agonist activity when AR is overexpressed.

Pharmacokinetics

Tmax: 0.5-3 hours. Half-life: 5.8 days (active metabolite N-desmethyl enzalutamide: 7.8 days). Protein binding: 97-98%. Metabolized by CYP2C8 (major) and CYP3A4. Steady-state by Day 28. Excreted in urine (71%) and feces (14%).

14. Clinical Studies

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

Pivotal Clinical Trials
Additional Resources
📋 All Enzalutamide Trials on ClinicalTrials.gov ↗ 📚 PubMed: Enzalutamide Clinical Trials ↗
Approved Tumor Types
Prostate Cancer