Darolutamide

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

Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, keto-darolutamide, 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.

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: Avoid concomitant use of Darolutamide with combined P-gp and strong or moderate CYP3A4 Inducers.

Combined P-gp and Strong CYP3A4 Inhibitors: Concomitant use of Darolutamide with a combined P-gp and strong CYP3A4 inhibitor increases Darolutamide exposure which may increase the risk of Darolutamide adverse reactions. Monitor patients more frequently for Darolutamide adverse reactions and modify Darolutamide dosage as needed.

BCRP (Breast Cancer Resistant Protein) 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.

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The safety and efficacy of Darolutamide have not been established in females. Based on its mechanism of action, Darolutamide can cause fetal harm and loss of pregnancy. Animal embryo-fetal developmental toxicology studies were not conducted with Darolutamide. There are no human data on the use of Darolutamide in pregnant females.

Darolutamide can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception.

There is no known specific antidote for Darolutamide overdose. The highest dose of Darolutamide studied clinically was 900 mg twice daily, equivalent to a total daily dose of 1800 mg. No dose limiting toxicities were observed with this dose.

Considering the saturable absorption and the absence of evidence for acute toxicity, an intake of a higher than recommended dose of Darolutamide is not expected to lead to systemic toxicity in patients with intact hepatic and renal function.

In the event of intake of a higher than recommended dose in patients with severe renal impairment or moderate hepatic impairment, if there is suspicion of toxicity, interrupt Darolutamide treatment and undertake general supportive measures until clinical toxicity has been diminished or resolved. If there is no suspicion of toxicity, Damid treatment can be continued with the next dose as scheduled.

Cytotoxic Chemotherapy

Do not store above 25°C temperature. Keep away from light and wet place. Keep out of reach of children.