Table 5.
Effect of abiraterone and enzalutamide on coadministrated drugs
| Drugs | Enzyme | Effects observed | Authors’ recommendations | References | ||
|---|---|---|---|---|---|---|
| Abiraterone Acetate | Dextromethorphan | CYP2D6 | AUC24 increased (2.9-fold) | If possible, switch to alternatives that are not metabolized through CYP2D6 Be aware that substrates of CYP2D6 are presumably more active. Be aware of side effects and toxicity. Consider dose reduction of concomitant CYP2D6 substrate with at least twofold Avoid use of CYP2D6 substrates with a narrow therapeutic index |
[14, 22, 26] | |
| Theophylline | CYP1A2 | No effect | Not clinically relevant: no change in medication is required | [14, 22, 26] | ||
| Pioglitazone | CYP2C8 | AUC24 increased (46 %) | If possible, switch to alternatives that are not metabolized through CYP2C8 Be aware that substrates of CYP2C8 are presumably more active. Be aware of side effects and toxicity Avoid use of CYP2C8 substrates with a narrow therapeutic index |
[14, 22] | ||
| Enzalutamide | Pioglitazone | CYP2C8 | AUCinf increased (20 %) | Not clinically relevant: no change in medication is required | [15, 20, 32] | |
| S-Warfarin | CYP2C9 | AUCinf decreased (56 %) | If possible, switch to alternatives that are not metabolized through CYP2C9 Be aware that substrates of CYP2C9 are presumably less active and elevate the dose based on efficacy Avoid use of CYP2C9 substrates with a narrow therapeutic index |
[15, 20, 32] | ||
| Omeprazole | CYP2C19 | AUCinf decreased (70 %) | If possible, switch to alternatives that are not metabolized through CYP2C19 Be aware that substrates of CYP2C19 are less active and elevate the dose based on efficacy Avoid use of CYP2C19 substrates with a narrow therapeutic index |
[15, 20, 32] | ||
| Midazolam | CYP3A4 | AUCinf decreased (86 %) | If possible, switch to alternatives that are not metabolized through CYP3A4 Be aware that substrates of CYP3A4 are substantially less active. The dose of CYP3A4 substrates should be adjusted to achieve comparable efficacy Avoid use of CYP3A4 substrates |
[15, 20, 32] | ||
| Dextromethorphan | CYP2D6 | AUCinf decreased (31 %) | Be aware that substrates of CYP2D6 are moderately less active Avoid concomitant use of CYP2D6 substrates with a narrow therapeutic index |
[15, 20] | ||
| Caffeine | CYP1A2 | AUCinf decreased (11 %) | Not clinically relevant: no change in medication is required | [15, 20] | ||
CYP cytochrome P450, AUC 24 area under the concentration–time curve from time zero to 24 h