Regorafenib - Overall Recommendations

Regorafenib CAN be Co-Administered with the Following Agents, IF Administered with Caution1

  • UGT1A1 (e.g. irinotecan ) and UGT1A9 substrates
  • Breast cancer resistance protein (BCRP) substrates (e.g. methotrexate ) and P-glycoprotein substrates (e.g. digoxin)
  • Antibiotics
  • Bile salt-sequestering agents (e.g. cholestyramine, Cholestagel)

Regorafenib CANNOT be Co-administered with the Following Agents1,2

  • Strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, dexamethasone, St. John’s wort)
  • Strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole, indinavir and ritonavir)
  • Strong UGT1A9 inhibitors (e.g. mefenamic acid, diflunisal and niflumic acid)

Additional Important Information when Prescribing Regorafenib

If the combination of regorafenib and strong CYP3A4 inducers cannot be avoided, increase the regorafenib dose gradually and monitor toxicity.3,4

If the combination of regorafenib and strong CYP3A4 inhibitors cannot be avoided, monitor regorafenib toxicity; dose adjustments are highly recommended.3,4


  1. European Medicines Agency. Regorafenib (STIVARGA). Summary of Product Characteristics. 2015.
  2. Food and Drug Administration. Regorafenib (STIVARGA) Prescribing information. 2015.
  3. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014; 15: e315-326.
  4. Teo YL, Ho HK, Chan A. Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. Br J Clin Pharmacol 2015; 79: 241-253.
Last update: 21 July 2015