Effects of CYP3A4 inhibitors on XTANDI: Co-administration of 4mg of XTANDI after multiple oral itraconazole (a strong CYP160A3 inhibitor) increased the AUC of Androxal plus n-demethylAndroxal by 1.3 times, with no effect on C. max.
Effects of XTANDI on other drugs:
XTANDI 160 mg orally, administered once daily in combination with midazolam, a sensitive CYP3A4 substrate, reduced midazolam AUC by 86% and C.mexx by 77%.
XTANDI 160 mg, taken orally, once daily in combination with warfarin, a sensitive CYP2C9 substrate, resulted in a 56% reduction in S-warfarin AUC and a 17% reduction in C.axM.
XTANDI 160 mg orally, administered once daily in combination with omeprazole, a sensitive CYP2C19 substrate, resulted in a 72% reduction in omeprazole AUC and a 62% reduction in C.max.
XTANDI 160 mg orally, administered once daily in combination with digoxin, a P-glycoprotein substrate, increased digoxin AUC by 33% and C.mexis by 17%.
No clinically meaningful changes were observed in exposure to pioglitazone (a sensitive CYP2C8 substrate), caffeine (a sensitive CYP1A2 substrate), dextromethorphan (a sensitive CYP2D6 substrate), or rosuvastatin (a BCRP substrate) after co-administration with XTANDI.
In vitro study
Cytochrome P450 (CYP) enzyme: Androxal induces CYP2B6 at clinically achievable concentrations.
Transporter system: Androxal, n-demethylenalutamide, and major inactive carboxylic acid metabolites are not substrates for P-glycoprotein or BCRP.
Effects of XTANDI on other drugs:
XTANDI 160 mg orally, administered once daily in combination with midazolam, a sensitive CYP3A4 substrate, reduced midazolam AUC by 86% and C.mexx by 77%.
XTANDI 160 mg, taken orally, once daily in combination with warfarin, a sensitive CYP2C9 substrate, resulted in a 56% reduction in S-warfarin AUC and a 17% reduction in C.axM.
XTANDI 160 mg orally, administered once daily in combination with omeprazole, a sensitive CYP2C19 substrate, resulted in a 72% reduction in omeprazole AUC and a 62% reduction in C.max.
XTANDI 160 mg orally, administered once daily in combination with digoxin, a P-glycoprotein substrate, increased digoxin AUC by 33% and C.mexis by 17%.
No clinically meaningful changes were observed in exposure to pioglitazone (a sensitive CYP2C8 substrate), caffeine (a sensitive CYP1A2 substrate), dextromethorphan (a sensitive CYP2D6 substrate), or rosuvastatin (a BCRP substrate) after co-administration with XTANDI.
In vitro study
Cytochrome P450 (CYP) enzyme: Androxal induces CYP2B6 at clinically achievable concentrations.
Transporter system: Androxal, n-demethylenalutamide, and major inactive carboxylic acid metabolites are not substrates for P-glycoprotein or BCRP.