Table 4.

Cytochrome P450 isoenzymes (CYPs) and transporters modulated by perpetrator drugs in edoxaban drug–drug interaction (DDI) studies

Type of study	Perpetrator drug	Metabolic CYP enzymes inhibited	Metabolic CYP enzymes induced	Transporters inhibited	Transporters induced
DDI with quinidine	Quinidine	Strong 2D6		P-gp; OCT2
Edoxaban (intravenous)	Quinidine	Strong 2D6		P-gp; OCT2
DDI with verapamil	Verapamil	Moderate 3A4; weak 1A2, 2D6		P-gp
DDI with dronedarone	Dronedarone	Moderate 3A4		P-gp
DDI with ketoconazole	Ketoconazole	Strong 3A4; weak 2C8, 2C19		P-gp
DDI with erythromycin	Erythromycin	Moderate 3A4		P-gp
DDI with cyclosporine	Cyclosporine	Weak 3A		P-gp; OATP1B1; BCRP
DDI with amiodarone	Amiodarone	Moderate 2C9; weak 2D6, 3A		P-gp
DDI with atorvastatin	Atorvastatin	Weak 3A4
DDI with esomeprazole	Esomeprazole	2C9, 2C19 (competitive)
DDI with rifampin	Rifampin		Strong 3A4; moderate 2B6, 2C8, 2C9, 2C19	P-gp; OATP1B1, OATP1B3	P-gp

This table is based on the draft US Food and Drug Administration DDI guidance [35] and the Indiana University DDI table [36]

BCRP breast cancer resistance protein, OATP organic anion-transporting polypeptide, OCT2 organic cation transporter 2, P-gp P-glycoprotein