Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men.

[8][4][5][9][10] It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration.

[4] Side effects of darolutamide added to castration may include fatigue, asthenia, pain in the arms and legs, and rash.

[4] Darolutamide is a nonsteroidal antiandrogen (NSAA), and acts as a selective antagonist of the androgen receptor (AR).

[15] and in Canada in 2020, Darolutamide is approved for use concurrently with a gonadotropin-releasing hormone (GnRH) agonist or antagonist or bilateral orchiectomy in the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) in men.

[19] Also, darolutamide showed significantly lower rate of grade 3-5 adverse events (AE) compared to both enzalutamide and apalutamide.

[7][20] Darolutamide is an expected teratogen and has a theoretical risk of birth defects in male infants if taken by women during pregnancy.

[10] It has been claimed to negligibly cross the blood–brain barrier, and hence is thought to have a reduced risk of seizures and other central side effects from off-target GABAA receptor inhibition.

[10] However, darolutamide monotherapy has subsequently been found to increase testosterone levels, a centrally mediated antiandrogenic action.

[23] Darolutamide has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently identified clinically-relevant F876L mutation that produces resistance to enzalutamide and apalutamide.

[31] Similarly, darolutamide shows no inhibition of a variety of other transporters (P-glycoprotein, MRP2, BSEP, OATs, OCTs, MATEs, OATP2B1, NTCP) at therapeutic concentrations.

[4] Exposure to darolutamide and ketodarolutamide increases in a nearly linear or dose-proportional manner across a dose range of 100 to 700 mg (or about 0.17- to 1.17-fold the recommended 600-mg dosage).

[10] However, a subsequent study of darolutamide monotherapy in men with prostate cancer found that it increased testosterone levels, a centrally mediated antiandrogenic action.

[33][34][35] P-Glycoprotein is known to play a major role in excluding drugs from the brain due to efflux back across the blood–brain barrier.

[4] In non-nmCRPC individuals with severe renal impairment not on dialysis, exposure to darolutamide was increased by about 2.5-fold relative to healthy people.

[4] In non-nmCRPC individuals with moderate hepatic impairment, darolutamide exposure was increased by about 1.9-fold compared to healthy controls.

[4] Darolutamide is a nonsteroidal compound and is structurally distinct from other marketed NSAAs, including enzalutamide and apalutamide.

[40] The U.S. Food and Drug Administration (FDA) approved darolutamide in July 2019, under the agency's priority review designation.

[8] Approval was based on ARAMIS,[41] a multicenter, double-blind, placebo-controlled clinical trial in 1,509 patients with non-metastatic castration resistant prostate cancer.

All patients received a gonadotropin-releasing hormone (GnRH) analog concurrently or had a previous bilateral orchiectomy.