Absorption: 30% absorbed following oral administration; absorption increased with food.
Distribution: Extensively distributed to tissues.
Protein Binding: Darolutamide– 92%; Keto-darolutamide– 99.8%.
Metabolism and Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme as well as by UGT1A1 and UGT1A9 to an active metabolite (keto-darolutamide). Primarily excreted in urine (63%, 7% as unchanged drug) and 32% excreted in feces (30% as unchanged drug).
Concurrent use with a combined P-glycoprotein and strong or moderate CYP3A4 inducer, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Concurrent use with a combined P-glycoprotein and strong CYP3A4 inhibitor, including itraconazole, may ↑ levels and the risk of toxicity; avoid concurrent use.
May ↑ levels of BCRP substrates, including rosuvastatin ; avoid concurrent use.
Instruct patient to take darolutamide as directed. Take missed doses as soon as remembered, but do not take two doses together to make up for a missed dose. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Inform patient of importance of continuing therapy with gonadotropin-releasing hormone during therapy with darolutamide.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise male patients with female partners of reproductive potential to use effective contraception and avoid breastfeeding during and for 1 wk after last dose. Inform patient that darolutamide may impair fertility.