Darolutamide

NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with: non-metastatic castration-resistant prostate cancer (nmCRPC). metastatic castration-sensitive prostate cancer (mCSPC). metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel. NUBEQA is indicated for the treatment of adult patients with: non-metastatic castration resistant prostate cancer (nmCRPC) metastatic castration-sensitive prostate cancer (mCSPC) metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel.

Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, ketodarolutamide, exhibited similar in vitro activity to darolutamide. In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro (approximately 1% activity compared to AR). Darolutamide decreased prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer.

Recommended Dosage: NUBEQA 600 mg orally twice daily. Swallow tablets whole. Take NUBEQA with food. For patients with mCSPC treated with NUBEQA in combination with docetaxel, administer the first cycle of docetaxel within 6 weeks after the start of NUBEQA treatment. Patients should also receive a gonadotropin-releasing hormone (GnRH) agonist or antagonist concurrently or have had bilateral orchiectomy. Severe Renal Impairment (not on hemodialysis): Recommended dosage is 300 mg twice daily. Moderate Hepatic Impairment: Recommended dosage is 300 mg twice daily.

None. None.

Ischemic Heart Disease: Optimize management of cardiovascular risk factors. Monitor for signs and symptoms of coronary artery disease. Discontinue NUBEQA for Grade 3-4 events. Seizure: Consider discontinuation of NUBEQA in patients who develop a seizure during treatment. Embryo-Fetal Toxicity: NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Ischemic Heart Disease Seizure In nmCRPC and mCSPC: The most common adverse reactions (>10% with a ≥2% increase over placebo), including laboratory test abnormalities, are increased AST, decreased neutrophil count, increased bilirubin, fatigue, and increased ALT. In mCSPC in combination with docetaxel: The most common adverse reactions (≥10% with a ≥2% increase over placebo) are constipation, rash, decreased appetite, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) are anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.

Combined P-gp and Strong or Moderate CYP3A Inducers: Avoid concomitant use. Combined P-gp and Strong CYP3A Inhibitors: Monitor patients more frequently for NUBEQA adverse reactions. BCRP Substrates: Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions and consider dose reduction of the BCRP substrate drug. OATP1B1 and OATP1B3 Substrates: Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. If used together, monitor patients more frequently for adverse reactions and consider dose reduction of these drugs.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).