Pharmacology & Mechanism
- A second-generation androgen receptor (AR) antagonist.
- Binds AR with high affinity, blocking:
- Androgen receptor binding,
- Nuclear translocation, and
- DNA transcription of AR-driven genes.
- Structurally distinct from enzalutamide/apalutamide → results in low blood–brain barrier penetration → reduced CNS side effects (e.g., seizures, cognitive impairment).
Indications
- Non-metastatic castration-resistant prostate cancer (nmCRPC).
- Metastatic castration-sensitive prostate cancer (mCSPC) in combination with ADT + docetaxel (triplet therapy).
Dosing
- 600 mg PO twice daily with food (two × 300 mg tablets).
- Continue ADT (GnRH agonist/antagonist or orchiectomy) during therapy.
Adverse Effects & Monitoring
- Common: fatigue, rash, hypertension, arthralgia.
- Less CNS toxicity vs enzalutamide/apalutamide (minimal seizure risk).
- Laboratory monitoring: liver function tests (rare hepatotoxicity), electrolytes, cardiovascular risk factors.
- Generally well tolerated compared to other AR antagonists.
Clinical Pearls for Pharmacists
- Food increases absorption → always administer with meals.
- Fewer drug–drug interactions compared to enzalutamide (weaker CYP inducer).
- Advantageous in patients with CNS comorbidities (seizures, cognitive decline).
- Used earlier in disease course (nmCRPC, mCSPC with docetaxel) to delay progression and improve survival.