NUBEQA

Indications

• Hormone-relapsed non-metastatic prostate cancer
• Non-metastatic castration-resistant prostate cancer

Dosage

Adults: The recommended dosage is 600 mg taken orally, twice daily.

Mechanism of action

Darolutamide competitively inhibits androgens from binding to androgen receptors (AR), preventing AR nuclear translocation and inhibiting AR-mediated transcription. This results in decreased proliferation of prostate cancer cells and reduction in tumor size. Its metabolite, keto-darolutamide, exhibits similar activity, further enhancing the drug's efficacy.

Pharmacodynamics

Darolutamide treats castrate-resistant prostate cancer by inhibiting cancer cell growth and significantly lowering PSA levels through its potent antagonism of androgen receptors. It also exhibits some activity as a progesterone receptor antagonist, though its clinical relevance remains uncertain.

Pharmacokinetics

Darolutamide has a molecular formula of C19H19ClN6O2. It is primarily metabolized by cytochrome P450 enzymes, and its pharmacokinetics can be affected by co-administration of certain drugs. Dose adjustments may be required in patients with renal or hepatic impairment, and severe interactions with other drugs can influence darolutamide exposure.

Adverse effects

• Acute coronary syndrome
• Asthenia
• Atherosclerosis
• Bone fracture
• Cardiogenic shock
• Heart failure
• Ischaemic heart disease
• Lethargy
• Malaise
• Pain
• Rash

Interactions

• dabrafenib+darolutamide: Severe (decreases exposure)
• mitotane+darolutamide: Severe (decreases exposure)
• stjohn’swort+darolutamide: Severe (decreases exposure)
• darolutamide+statins: Severe (increases exposure)
• darolutamide+atorvastatin: Severe (increases exposure)
• darolutamide+fluvastatin: Severe (increases exposure)
• darolutamide+rosuvastatin: Severe (increases exposure)
• darolutamide+sulfasalazine: Severe (increases exposure)
• darolutamide+topotecan: Severe (increases exposure)
• bosentan+darolutamide: Severe (decreases exposure)

Precautions

• Caution in severe renal impairment
• Caution in moderate and severe hepatic impairment
• Men should use condoms during treatment and for 3 months after stopping if their partner is pregnant
• Patients should be counselled on the effects on driving and skilled tasks due to the risk of psychiatric or neurological events, including seizures

Pregnancy

Manufacturer advises men to use condoms during treatment and for 3 months after stopping if their partner is pregnant.

Breast-feeding

Women of childbearing potential should avoid handling darolutamide tablets.

Storage

Store in a cool, dry place, away from light.

Formulations

• Tablet

Mechanism of action

The actions of androgens on androgen receptors (AR) potentiate the growth and survival of prostate cancer cells. Darolutamide competitively inhibits androgens from binding to their receptors, inhibiting AR nuclear translocation, as well as AR-mediated transcription. The end result of these processes is a decrease in prostate cancer cell proliferation and tumor size. Its main metabolite, keto-darolutamide, shows similar pharmacological activity to the parent drug, darolutamide. Darolutamide has been found to bind more tightly to the AR receptor than [apalutamide] and [enzalutamide], which are other androgen receptor antagonists. Darolutamide can act as a progesterone receptor (PR) antagonist in the laboratory setting with approximately 1% activity when compared to its actions at the androgen receptor. The clinical relevance is not known at this time.

Pharmacodynamics

Darolutamide, through its downstream effects on cancer cell growth, treats castrate-resistant prostate cancer. It inhibits cancer cell growth and markedly lowers prostate specific antigen (PSA) levels through potent androgen receptor antagonism.