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
Adverse 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%)
Mechanism 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