Nubeqa Darolutamide Tablets

1. Indications and Usage
Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC):
Indicated for the treatment of adult patients with nmCRPC at high risk of metastasis .
Metastatic Hormone-Sensitive Prostate Cancer (mHSPC):
Indicated for the treatment of adult patients with mHSPC, in combination with androgen deprivation therapy (ADT) and docetaxel .
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: 600 mg (two 300 mg tablets) twice daily, equivalent to a total daily dose of 1200 mg .
Treatment Duration: Continue until disease progression or unacceptable toxicity.
Administration Instructions:
Swallow tablets whole with water; do not crush, chew, or split.
Must be taken with food to ensure adequate absorption and bioavailability .
Concomitant Therapy: Must be used in combination with a GnRH analogue (continuous medical castration) or in patients who have undergone bilateral orchiectomy .
Missed Dose: If a dose is missed, take it as soon as possible on the same day with food. Resume the normal schedule the following day. Do not take a double dose .
Dose Adjustments:
Reduce dose (to 300 mg twice daily) for intolerable Grade ≥3 adverse reactions .
Reduce dose for severe renal impairment (eGFR 15–29 mL/min) or moderate hepatic impairment (Child-Pugh B) .
3. Mechanism of Action
Androgen Receptor (AR) Inhibition:
Darolutamide is a potent, small-molecule AR antagonist that binds directly to the ligand-binding domain of the AR.
Blocking Signaling Pathways:
It inhibits multiple steps in the AR signaling pathway:
1. Inhibits the binding of testosterone and dihydrotestosterone (DHT) to the AR.
2. Inhibits the nuclear translocation of the activated AR.
3. Inhibits the binding of the AR to DNA, thereby blocking AR-mediated transcription and tumor cell growth .
Structural Distinctiveness:
Unlike other AR inhibitors, darolutamide has a unique chemical structure with lower lipophilicity, which limits its ability to cross the blood-brain barrier .
4. Safety and Warnings
Ischemic Cardiovascular Events:
May increase the risk of ischemic cardiovascular and cerebrovascular events. Monitor for symptoms and optimize risk factors .
Falls and Fractures:
Increased risk of falls and fractures. Assess fall risk and consider bone-modifying agents .
Embryo-Fetal Toxicity:
Males with female partners of reproductive potential must use effective contraception during treatment and for 1 week after the final dose.
Seizures:
While the risk is lower than other AR inhibitors, seizures have been reported. Monitor patients for signs of seizure activity .
5. Adverse Reactions
Most Common (Incidence >10%):
Fatigue, asthenia, limb pain, rash, and hematuria .
Laboratory Abnormalities:
Increased AST, increased ALT, neutropenia, and anemia (especially when combined with docetaxel) .
6. Drug Interactions
Transporter Proteins (BCRP, OATP):
Darolutamide may increase plasma concentrations of BCRP and OATP substrates (e.g., rosuvastatin, methotrexate). Avoid concomitant use with rosuvastatin .
CYP Enzymes:
Darolutamide is metabolized by CYP3A4 and UGT2B7. Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin) .
P-gp Inhibitors:
Concomitant use with strong P-gp inhibitors may increase darolutamide exposure .
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Darolutamide.
Available Strength: 300 mg tablets.
Appearance: White to off-white, capsule-shaped, film-coated tablets .
Storage: Store at room temperature (20°C–25°C / 68°F–77°F) .