Effect of Strong CYP3A4 Inducers on Effect of Strong CYP3A4 Inhibitors on Regorafenib
Co-administration of a strong CYP3A4 inhibitor with STIVARGA increased the plasma concentrations of regorafenib and
decreased the plasma concentrations of the active metabolites M-2 and M-5 [see Clinical Pharmacology (12.3)], and may
lead to increased toxicity. Avoid concomitant use of STIVARGA with strong CYP3A4 inhibitors (e.g. clarithromycin,
grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole).
Co-administration of a strong CYP3A4 inducer with REGONIB decreased the plasma concentrations of regorafenib,
increased the plasma concentrations of the active metabolite M-5, and resulted in no change in the plasma concentrations
of the active metabolite M-2 , and may lead to decreased efficacy. Avoid concomitant
use of STIVARGA with strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John’s
Effect of Strong CYP3A4 Inhibitors on Regorafenib : Co-administration of a strong CYP3A4 inhibitor with REGONIB increased the plasma concentrations of regorafenib and
decreased the plasma concentrations of the active metabolites M-2 and M-5 , and may
lead to increased toxicity. Avoid concomitant use of STIVARGA with strong CYP3A4 inhibitors (e.g. clarithromycin,
grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole).
Effect of Regorafenib on Breast Cancer Resistance Protein (BCRP) Substrates
Co-administration of REGONIB with a BCRP substrate increased the plasma concentrations of the BCRP substrate. Monitor patients closely for signs and symptoms of exposure related toxicity to the BCRP
substrate (e.g. methotrexate, fluvastatin, atorvastatin). Consult the concomitant BCRP substrate product information when
considering administration of such products together with REGONIB .