Table 3.
Metabolic enzymes and transporters involved in DDI with darolutamide—darolutamide as an effector
| Darolutamide effector of: | Potential DDI | Effect on AUC and Cmax | Clinical implication | Interaction potential | References |
|---|---|---|---|---|---|
| CYP3A4 (weak inducer) | Midazolam; CYP3A4 substrate |
AUC∞: 29% decrease Cmax: 32% decrease |
Concentrations of CYP3A4 substrates may decrease due to induction of CYP3A4; no change in medication is required Care should be taken when darolutamide is concomitantly given with CYP3A4 substrates with a narrow therapeutic index |
Minor | [9, 10, 39] |
| Cabazitaxel; CYP3A4 substrate | No effect | [45] | |||
| Ipatasertib; CYP3A4 substrate |
AUC24: 8% decrease Cmax: 21% decrease |
[46] | |||
| BCRP (inhibitor) | Rosuvastatin; BCRP, OATP substrate |
AUC24: 5.2-fold increase Cmax: 4.9-fold increase |
Avoid combination if possible Switch to alternatives that are not BCRP substrates. If coadministration is clinically necessary, close monitoring for AEs is required |
Major | [9, 10, 39] |
| OATP1B1 (weak inhibitor) | Rosuvastatin; BCRP, OATP substrate |
AUC24: 5.2-fold increase Cmax: 4.9-fold increase |
Concentrations of OATP substrates may increase. If coadministered with OATP substrates, monitor for AEs | Minor | [9, 10, 39, 47] |
| OATP1B3 (inhibitor) | Docetaxel; CYP3A4, OATP1B1, and OATP1B3 substrate |
AUC12,ss: 6% increase Cmax: 15% increase |
Concentration of docetaxel may slightly increase when coadministered with darolutamide. However, no clinically significant effect is expected | ||
| P-gp (in vitro inhibitor) | Dabigatran; P-gp substrate | No effect | No clinically significant effect is expected when darolutamide is concomitantly given with P-gp substrates; no change in medication is required | No interaction potential | [9, 10, 39] |
AE adverse effect, AUC∞ area under the plasma concentration-time curve from time 0 to infinity, AUC12,ss area under the concentration-time curve from zero to 12 hours in steady state, AUC24 area under the concentration-time curve from zero to 24 hours, BCRP breast cancer resistance protein, Cmax maximum plasma drug concentration, CYP cytochrome P40, DDI drug-drug interaction, OATP organic anion transporting polypeptides, P-gp P-glycoprotein