NUBEQA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NUBEQA (NUBEQA).
Androgen receptor inhibitor; binds to the androgen receptor and inhibits nuclear translocation, DNA binding, and recruitment of coactivators, thereby reducing prostate cancer cell proliferation.
| Metabolism | Primarily metabolized by CYP3A4 and also by CYP2C8 and UGT1A1 to a lesser extent. |
| Excretion | Primarily excreted as unchanged drug via feces (approximately 63.7%) and urine (approximately 23.8%); minimal biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 20 hours; supports once-daily dosing. |
| Protein binding | Approximately 97% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Apparent volume of distribution is approximately 98 L (1.2 L/kg for a 80 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 21% (fasted state); increased by 2.6-fold with a high-fat meal. |
| Onset of Action | Androgen receptor inhibition occurs within 2 to 4 hours post oral dose; clinical effects (e.g., prostate-specific antigen decline) observed within 2 to 4 weeks. |
| Duration of Action | Sustained androgen receptor inhibition for 24 hours with once-daily dosing; continuous therapy required for maintained effect. |
600 mg orally twice daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Not recommended for GFR <30 mL/min. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Not recommended. Child-Pugh C: Contraindicated. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No dose adjustment required based on age alone; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NUBEQA (NUBEQA).
| Breastfeeding | It is unknown whether darolutamide or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment with NUBEQA and for at least 1 week after the final dose. The milk-to-plasma ratio (M/P ratio) is not available. |
| Teratogenic Risk | NUBEQA (darolutamide) is contraindicated in pregnancy. Based on its mechanism of action (androgen receptor inhibition), it can cause fetal harm. Animal studies have shown adverse developmental effects including embryotoxicity and malformations in rats at exposures below human clinical exposure. No adequate human data exist. It should not be used in pregnant women or those planning to become pregnant. If exposure occurs during pregnancy, the patient should be apprised of the potential hazard to the fetus. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Pregnancy","Severe hepatic impairment (Child-Pugh C)"]
| Precautions | ["Ischemic cardiovascular events","Hypertension","Fractures","Seizures","Posterior reversible encephalopathy syndrome (PRES)","Hypersensitivity reactions","Fetal toxicity"] |
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| Fetal Monitoring | Pregnancy testing should be performed in females of reproductive potential prior to initiation of NUBEQA. If a female becomes pregnant while on treatment, she should be informed of the risk to the fetus. No specific fetal monitoring is recommended because use during pregnancy is contraindicated. In males with female partners of reproductive potential, effective contraception should be used during treatment and for 1 week after the last dose to prevent fetal exposure. |
| Fertility Effects | NUBEQA may impair fertility in males based on animal studies where reduced testicular weight and seminiferous tubule degeneration were observed. In humans, no dedicated fertility studies have been conducted; however, as an androgen receptor inhibitor, it may affect spermatogenesis. The effect on female fertility is not known, but due to its mechanism, potential for impairment exists. |