Darolutamide is approved for use concurrently with a gonadotropin releasing hormone (GnRH) antagonist or bilateral orchiectomy in the treatment of non-metastatic castration -resistant prostate cancer (nmCRPC) in men. It is used at a dosage of 600 mg orally twice per day (1,200 mg/day total) with food. In individuals with severe renal impairment or moderate hepatic impairment, This is used at a dosage of 300 mg orally twice per day (600 mg/day total) with food. No dosage adjustment is needed for mild to moderate renal impairment or mild hepatic impairment, whereas appropriate dosage adjustment for end-stage kidney disease and severe hepatic impairment is unknown.
Two 2020 meta-analyses reported that enzalutamide and apalutamide seemed to be more effective than darolutamide in improving metastasis-free survival (MFS), however 2021 matched adjusted indirect comparison showed no significant differences between drugs in terms of MFS. According to the 2021 meta-analysis, An this was ranked first in terms of improving overall survival (OS). Also, darolutamide showed significantly lower rate of grade 3-5 adverse events (AE) compared to both enzalutamide and apalutamide.
Darolutamide has no contraindication in men. However, the medication may have teratogenic effects in male fetuses due to its antiandrogenic effects and hence should not be used by women who are pregnant.
The most common side effects of darolutamide in clinical trials (≥2% incidence) in castrated men included fatigue and asthenia (16% vs. 11% for placebo), pain in extremities (6% vs. 3% for placebo), and rash (3% vs. 1% for placebo). Darolutamide was also associated with higher incidences of ischemic heart disease (4.0% vs. 3.4% for placebo) and heart failure (2.1% vs. 0.9% for placebo). In terms of laboratory test abnormalities, darolutamide was associated with decreased neutrophil count (20% vs. 9% for placebo), increased aspartate aminotransferase (AST) (23% vs. 14% for placebo; Grade 3–4: 0.5% vs. 0.2% for placebo), and increased bilirubin (16% vs. 7% for placebo). In the clinical studies, 88% of patients treated with darolutamide were 65 years or older.
No seizures have been observed with darolutamide in clinical trials. Darolutamide is an expected teratogen and has a theoretical risk of birth defects in male infants if taken by women during pregnancy It may impair male fertility. When used as a monotherapy (i.e., without surgical or medical castration) in men, NSAAs are known to produce feminizing breast changes including breast tenderness and gynecomastia..
Darolutamide has been studied at a dosage of up to 1,800 mg/day in clinical trials. There were no dose-limiting toxicities seen at this dosage. Due to its saturable absorption and lack of acute toxicity, overdose of darolutamide is not expected to result in systemic toxicity in people with intact hepatic and renal function. There is no specific antidote for overdose of darolutamide. In the event of darolutamide overdose, if there is no toxicity, treatment can be continued as normal. If there is suspicion of toxicity, general supportive measures should be undertaken until clinical toxicity has decreased or resolved and then treatment may be continued