Products
Darolutamide was approved in the US in 2019 and in the EU and Switzerland in 2020 in film-coated tablet form (Nubeqa).
Structure and properties
Darolutamide (C19H19ClN6O2, Mr = 398.8 g/mol) exists as a white to grayish or yellowish-white crystalline powder and is practically insoluble in water. The drug has a nonsteroidal structure and is structurally distinct from other steroidal and nonsteroidal antiandrogens. Darolutamide consists of a 1:1 mixture of two pharmacologically active diastereomers (,-darolutamide and ,-darolutamide) that interconvert through the active metabolite keto-darolutamide.
Effects
Darolutamide (ATC L02BB06) has antitumor properties. It reduces cell proliferation and tumor size. The effects are due to competitive antagonism at the androgen receptor. It prevents androgen binding to the receptor, its translocation and transcription mediated by it. Reduced crossing of the blood–brain barrier into the central nervous system represents an advantage.
Indications
In combination with androgen deprivation therapy for the treatment of adult patients with nonmetastatic castration-resistant prostate cancer (NM-CRPC) who are at high risk for developing metastases.
Dosage
According to the SmPC. Tablets are taken twice daily with meals.
Contraindications
- Hypersensitivity
- Women who are pregnant or may become pregnant.
Full precautions can be found in the drug label.
Interactions
Darolutamide is metabolized primarily by CYP3A4, is a substrate of P-glycoprotein, and is an inhibitor of BCRP.
Adverse effects
The most common potential adverse effects include fatigue, pain in the extremities, and a rash.
