Darolutamide
NUBEQA
What it isNonsteroidal androgen-receptor antagonist; nonmetastatic castration-resistant and metastatic hormone-sensitive prostate cancer.
Why this oneMinimal blood-brain-barrier penetration produces fewer CNS effects and less seizure concern than apalutamide or enzalutamide.
What limits itFatigue, rash, and cardiovascular events can limit treatment; P-gp, BCRP, and CYP3A4 interactions alter exposure.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Non-metastatic castration-resistant prostate cancer (nmCRPC) | Adults | 600 mg (2 x 300 mg tabs) BID with food | 600 mg BID | 600 mg BID |
| Metastatic castration-sensitive prostate cancer (mCSPC), in combination with docetaxel | Adults | 600 mg BID with food (first docetaxel cycle within 6 wk of starting) | 600 mg BID | 600 mg BID |
Renal Severe (eGFR 15-29, not on hemodialysis): 300 mg BID. Mild-moderate (eGFR 30-89): no adjustment. ESRD (eGFR <15): unknown
Hepatic Moderate (Child-Pugh B): 300 mg BID. Mild: no adjustment. Severe (Child-Pugh C): unknown
For >=Grade 3 or intolerable adverse reaction: withhold or reduce to 300 mg BID; resume 600 mg BID when back to baseline. Do not reduce below 300 mg BID. Discontinue for Grade 3-4 ischemic heart disease
Instructions
- Swallow tablets whole, take with food
- Continue GnRH agonist/antagonist concurrently unless prior bilateral orchiectomy
- Missed dose: take as soon as remembered before next scheduled dose; do not double up
- Continue until disease progression or unacceptable toxicity
Cautions
- Ischemic heart disease (incl. fatal): optimize CV risk factors, monitor; discontinue for Grade 3-4 events
- Seizure (0.2-0.8%): consider discontinuation if seizure occurs; caution with activities where loss of consciousness could cause harm
- Embryo-fetal toxicity: males with female partners of reproductive potential use effective contraception during and 1 week after treatment
Adverse reactions
- nmCRPC/mCSPC: increased AST, decreased neutrophils, increased bilirubin, fatigue, increased ALT
- With docetaxel (mCSPC): constipation, rash, decreased appetite, hemorrhage, weight increase, hypertension; labs (>=30%): anemia, hyperglycemia, decreased lymphocytes/neutrophils, increased AST/ALT, hypocalcemia
Pregnancy Not established in females; can cause fetal harm and pregnancy loss based on mechanism; no human data
Lactation Not established in females; no data on presence in human milk or effects on infant/milk production
NO BOXED WARNINGS
Principal riskNo FDA boxed warning.
Cost, est. cash$500–$15,000/month
Generic entry2038 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryNot assigned — PLLR-era drug
Defining liabilityThrombotic, metabolic, hepatic, skeletal or reproductive toxicity varies by hormonal target.
Mechanism of action: Darolutamide ballicule
