Table 2.

Major drug interactions with regorafenib.

Inducers of CYP3A4*	Inhibitors of CYP3A4^	CYP2C9 inhibition#	UGT1A1 inhibitor&
• Carbamazepine • Isoniazid • Phenobarbital • Phenytoin/fosphenytoin • Rifampin • St John’s wort (Hypericum perforatum)	• Boceprevir • Clarithromycin • Conivaptan • Grapefruit juice • Ketoconazole • Indinavir • Itraconazole • Nefazodone • Nelfinavir • Posaconazole • Ritonavir • Saquinavir • Telaprevir • Telithromycin • Voriconazole	• Warfarin	• Irinotecan

^*Inducers of CYP3A4 may decrease exposure to regorafenib and exposure to M-2 and M-5 metabolites may increase.

^{^}Inhibitors of CYP3A4 may increase exposure to regorafenib and exposure to M-2 and M-5 metabolites may decrease.

^#Regorafenib inhibits CYP2C9; concomitant administration of drugs that are CYP2C9 substrates may result in increased exposure of that drug.

^&Regorafenib is a UGT1A1 inhibitor: concomitant use with irinotecan may result in increased irinotecan exposure.

CYP2C9, cytochrome P450 family 2 subfamily C member 9; CYP3A4, cytochrome P450 3A4; M-2, demethylated N-oxide; M-5, N-oxide; UGT1A1, UDP-glucuronosyltransferase 1A1.