Darolutamide — Drug Monograph

Brand names: Nubeqa

Drug class: Hormonal Agent

Mechanism of Action

Darolutamide is a second-generation androgen receptor (AR) antagonist. It competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated DNA binding. Unlike other AR antagonists like enzalutamide, darolutamide has a distinct chemical structure that results in very low blood-brain barrier penetration. This reduces the risk of central nervous system-related side effects, such as seizures or cognitive impairment, while maintaining potent suppression of prostate cancer cell growth.

FDA Indications

• Treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC)
• Treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Common Side Effects

• Fatigue
• Pain in extremity
• Rash
• Neutropenia
• Increased AST/ALT
• Increased bilirubin
• Ischemic heart disease (in combination with docetaxel)

Clinical Pearl

Darolutamide is often favored over enzalutamide or apalutamide in patients at high risk for falls or seizures, as it has the lowest CNS penetration of the class. In the ARAMIS trial for nmCRPC, the side effect profile was nearly identical to placebo except for a slight increase in fatigue. Remember the food requirement: absorption is significantly decreased in the fasting state. It is now standard of care to combine it with docetaxel for "triplet therapy" in metastatic hormone-sensitive…

Related Therapies & Mechanisms

• Abiraterone Acetate (Zytiga) — Hormonal Agent · Prostate
• Apalutamide (Erleada) — Hormonal Agent · Prostate
• Bicalutamide (Casodex) — Hormonal Agent · Prostate
• Degarelix (Firmagon) — Hormonal Agent · Prostate