Darolutamide is indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

Darolutamide is an androgen receptor (AR) inhibitor. It works by competitively blocking the binding of androgens to the androgen receptor, preventing the receptor from moving into the cell nucleus and stopping AR-mediated gene transcription. A major active metabolite, keto-darolutamide, shows similar activity to darolutamide in laboratory studies. Additionally, darolutamide acts as a progesterone receptor (PR) antagonist in vitro, although its activity is much lower compared with its effect on androgen receptors.

In experimental studies, darolutamide reduced the proliferation of prostate cancer cells and decreased tumor size in mouse models implanted with human prostate cancer tumors.

The recommended dose of Darolutamide is 600 mg (two 300 mg tablets) administered orally twice daily, equivalent to a total dose of 1200 mg. Swallow tablets whole with food. Advice patients to take any missed dose as soon as they remember prior to the next scheduled dose, and not to take two doses together to make up for a missed dose. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Combined P-gp and Strong or Moderate CYP3A Inducers: Concomitant use of Darolutamide with medicines that act as both P-gp and strong or moderate CYP3A inducers should be avoided because they may reduce the effectiveness of Darolutamide.

Combined P-gp and Strong CYP3A4 Inhibitors: Using Darolutamide together with drugs that inhibit both P-gp and strong CYP3A4 may increase the exposure to Darolutamide, which can raise the risk of adverse effects. Patients should be monitored closely, and the dose of Darolutamide may need adjustment if necessary.

BCRP (Breast Cancer Resistance Protein) Substrates: Avoid combining Darolutamide with medicines that are BCRP substrates whenever possible. If they must be used together, patients should be monitored carefully for side effects, and the dose of the BCRP substrate drug may need to be reduced.

• Fatigue
• Pain in the extremities
• Skin rash 

The safety and effectiveness of Darolutamide in females have not been established. Based on its mechanism of action, Darolutamide may cause fetal harm or pregnancy loss. There are no available human data regarding the use of Darolutamide in pregnant women, and embryo-fetal toxicity studies in animals have not been conducted.

Darolutamide may cause harm to a developing fetus and could lead to pregnancy loss. Male patients who have female partners of reproductive potential should use effective contraception during treatment.

There is no specific antidote available for Darolutamide overdose. In clinical studies, the highest dose evaluated was 900 mg twice daily (a total of 1800 mg per day), and no dose-limiting toxicities were observed.

Because Darolutamide absorption becomes saturated and there is no evidence of acute toxicity, taking a higher than recommended dose is not expected to cause systemic toxicity in patients with normal liver and kidney function.

However, in patients with severe kidney impairment or moderate liver impairment, if a higher dose is taken and toxicity is suspected, treatment should be temporarily stopped and supportive care provided until symptoms improve. If no toxicity occurs, treatment may continue with the next scheduled dose.

Cytotoxic Chemotherapy

Store at a temperature below 25°C. Protect from light and moisture. Keep out of the reach of children.