Regorafenib (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- REGORAFENIB
- STIVARGA
Boxed Warning
• Severe and sometimes fatal hepatotoxicity has occurred in clinical trials [see Warnings and Precautions (5.1)]. • Monitor hepatic function prior to and during treatment [see Warnings and Precautions (5.1)]. • Interrupt and then reduce or discontinue STIVARGA for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence [see Dosage and Administration (2.2)].
Contraindications
None.
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in the labeling: •Hepatotoxicity [see Warnings and Precautions (5.1)] •Infections [see Warnings and Precautions (5.2)] •Hemorrhage [see Warnings and Precautions (5.3)] •Gastrointestinal Perforation or Fistula [see Warnings and Precautions (5.4)] •Dermatological Toxicity [see Warnings and Precautions (5.5)] •Hypertension [see Warnings and Precautions (5.6)] •Cardiac Ischemia and Infarction [see Warnings and Precautions (5.7)] •Reversible Posterior Leukoencephalopathy Syndrome (RPLS) [see Warnings and Precautions (5.8)]
Mechanism of Action
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAF V600E, SAPK2, PTK5, Abl and CSF1R at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model and inhibition of tumor growth in several mouse xenograft models including some for human colorectal carcinoma, gastrointestinal stromal and hepatocellular carcinoma. Regorafenib also demonstrated anti-metastatic activity in a mouse xenograft model and two mouse orthotopic models of human colorectal carcinoma.
Overdosage
The highest dose of STIVARGA studied clinically is 220 mg per day. The most frequently observed adverse drug reactions at this dose were dermatological events, dysphonia, diarrhea, mucosal inflammation, dry mouth, decreased appetite, hypertension, and fatigue. There is no known antidote for STIVARGA overdose. In the event of suspected overdose, interrupt STIVARGA, institute supportive care, and observe until clinical stabilization.