Darolutamide

Indications

Darolutamide is used for: Prostate Cancer

Adult Dose

Prostate Cancer Indicated for nonmetastatic castration-resistant prostate cancer (nmCRPC) 600 mg PO BID Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had a bilateral orchidectomy Hepatic impairment Mild (Child-Pugh Class A): No dosage adjustment necessary Moderate (Child-Pugh Class B): Reduce to 300 mg PO BID Severe (Child-Pugh Class C): Pharmacokinetics unknown

Child Dose

Renal Dose

Renal impairment Mild or moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment necessary Severe (eGFR 15-29 mL/min/1.73 m2) who are not receiving hemodialysis: Reduce to 300 mg PO BID End-stage renal disease (eGFR ?15 mL/min/1.73 m2): Pharmacokinetics unknown

Administration

Oral Administration Swallow tablets whole with food

Contra Indications

Hypersensitivity

Precautions

Based on its mechanism of action, fetal harm and loss of pregnancy may occur when administered to a pregnant women

Pregnancy-Lactation

Pregnancy Safety and efficacy have not been established in females Based on its mechanism of action, fetal harm and loss of pregnancy may occur Animal embryofetal developmental toxicology studies were not conducted with darolutamide There are no human data on the use in pregnant females Contraception Males: Based on the mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose Infertility Males: Based on animal studies, fertility may be impaired in males of reproductive potential Lactation Safety and efficacy have not been established in females There are no data on the presence of darolutamide or its metabolites in human milk, the effect on the breastfed child, or the effect on milk production

Interactions

Side Effects

Side effects of Darolutamide : All grades of severity are listed unless otherwise indicated >10% AST increased (23%) Decreased neutrophil count (20%) Fatigue (16%) Bilirubin increased (16% 1-10% Pain in extremity (6%) Ischemic heart disease (4%) Rash (3%) Heart failure (2.1%) Grade >3 Neutrophil count decreased (4%) <1% Grade >3 Fatigue (0.6%) AST increased (0.5%) Rash (0.1%) Bilirubin increased (0.1%)

Mode of Action

Androgen receptor (AR) inhibitor; competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription Keto-darolutamide (major metabolite) exhibited similar in vitro activity In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro Also, decreases prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer