Darolutamide
Darolutamide is a second-generation androgen-receptor antagonist for prostate cancer with a distinct chemical structure and low blood-brain-barrier penetration. This gives it a favourable CNS side-effect profile, with less fatigue, seizure, and fall risk than other agents in its class.
01 Overview
Marketed as Nubeqa, darolutamide was studied in the ARAMIS and ARASENS trials, showing improved survival with a tolerability profile notable for minimal CNS effects. Its low brain penetration underlies fewer seizures and less fatigue.
It is generally well tolerated, though it shares class effects such as fatigue and can raise the risk of certain events when combined with androgen-deprivation therapy.
02 Mechanism
High-affinity androgen-receptor antagonist that blocks androgen binding and receptor function; its polar structure limits blood-brain-barrier crossing, reducing central side effects.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Prostate cancer | 1200 mg/day | Oral | 600 mg twice daily with food |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved survival with low CNS burdenProlongs metastasis-free and overall survival with fewer central side effects than peers. | Survival benefit in RCTs | Clinical | |
| Favourable tolerabilityLow blood-brain-barrier penetration means less seizure, fatigue, and fall risk than other second-generation antagonists. | Fewer CNS effects | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| FatigueTiredness, generally less than with enzalutamide or apalutamide. | Mild | Common | Clinical | |
| Ischaemic heart events (with ADT)Slightly increased cardiac ischaemic and cardiac-failure events in combination therapy. | Moderate | Uncommon | Clinical |