Oncology Drug Reference Sheet: Darolutamide

January 26, 2023 by Chelsea Backler MSN, APRN, AGCNS-BC, AOCNS®, VA-BC

On August 5, 2022, the U.S. Food and Drug Administration approved darolutamide (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-tablets-metastatic-hormone-sensitive-prostate-cancer) (Nubeqa^®) in combination with docetaxel in adults with metastatic hormone-sensitive prostate cancer (mHSPC). The approval was based on clinical trial findings demonstrating that the agent improved overall survival and significantly delayed time to pain progression compared to placebo.

Category/Class

Androgen receptor inhibitor

Darolutamide competitively inhibits androgens from binding to their receptors (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf), restricting AR nuclear translocation as well as AR-mediated transcription, which decreases cancer cell proliferation and tumor growth.

Adults with mHSPC or nonmetastatic castration-resistant prostate cancer (nmCRPC). Darolutamide is indicated in combination with docetaxel (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) in mHSPC only.

Take two tablets (300 mg each) by mouth with food, twice daily. For patients with mHSPC receiving combination treatment with docetaxel, administer the first docetaxel cycle (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) within six weeks of starting darolutamide.

nmCRPC: More than 2% of patients experienced (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) increased AST or bilirubin, decreased neutrophil count, fatigue, pain in extremity, and rash.
mHSPC: More than 10% of patients reported (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) constipation, decreased appetite, rash, hemorrhage, weight gain, and hypertension. More than 30% experienced (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) anemia, hyperglycemia, decreased lymphocyte or neutrophil count, increased AST or ALT, and hypocalcemia.

Concomitant use with darolutamide may increase toxicities (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) from breast cancer–resistance protein (BCRP) substrates. Concomitant use of darolutamide with a combined P-gp and strong or moderate CYP3A4 inducer may decrease darolutamide activity (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf). Concomitant use of darolutamide with a combined P-gp and strong CYP3A4 inhibitor may increase risk of adverse reactions (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf). See the sidebar for more details.

In the drug’s clinical trials, no differences in safety or efficacy (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) were found in patients older than age 65 compared to younger patients. Patients with severe renal or moderate hepatic impairment should receive (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) a reduced dose. Because of the possible impact on fertility, discuss preservation options (https://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf) with patients of reproductive potential prior to initiating treatment.

Topics:

Drug	Interaction	Recommendation
Combined P-gp + strong or moderate CYP3A4 inducer	May decrease darolutamide activity	Avoid concomitant use.
Combined P-gp + CYP3A4 inhibitor	May increase darolutamide-related toxicities	Monitor patients closely for adverse reactions and modify darolutamide dose as needed.
BCRP substrates	May increase risk of BCRP substrate–related toxicities	Avoid concomitant use when possible; if the agents must be used together, monitor patients closely for adverse reactions and consider reducing BCRP substrate dosages.