Regorafenib

What it is and how it works

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.

Indications

is a kinase inhibitor indicated for the treatment of adult patients with: • Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. • Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. • Hepatocellular carcinoma (HCC) who have been previously treated with sorafenib Colorectal Cancer STIVARGA is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. Gastrointestinal Stromal Tumors STIVARGA is indicated for the treatment of adult patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Dosage and administration (summary)

• Recommended dose: 160 mg orally, once daily for the first 21 days of each 28-day cycle. • Take STIVARGA after a low-fat meal. ( 2.1 , 12.3 ) Recommended Dose The recommended dose is 160 mg STIVARGA (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle. Continue treatment until disease progression or unacceptable toxicity. Take STIVARGA at the same time each day. Swallow tablet whole with water after a low-fat meal that contains less than 600 calories and less than 30% fat . Do not take two doses of STIVARGA on the same day to make up for a missed dose from the previous day.

Contraindications

None. None.

Warnings and precautions

• Hepatotoxicity : Monitor liver function tests. Withhold and then reduce or discontinue STIVARGA based on severity and duration. • Infections : Withhold STIVARGA in patients with worsening or severe infections. • Hemorrhage : Permanently discontinue STIVARGA for severe or life-threatening hemorrhage. • Gastrointestinal perforation or fistula : Discontinue STIVARGA. • Dermatologic toxicity : Withhold and then reduce or discontinue STIVARGA depending on severity and persistence of dermatologic toxicity.

Pregnancy

Pregnancy Risk Summary Based on animal studies and its mechanism of action, STIVARGA can cause fetal harm when administered to a pregnant woman. There are no available data on STIVARGA use in pregnant women.

Storage and supply

How Supplied STIVARGA (regorafenib) is supplied as 40 mg tablets that are light pink, oval-shaped, film-coated tablets, debossed with 'BAYER' on one side and '40' on the other side in the following: • Packages containing three bottles, with each bottle containing 28 tablets, for a total of 84 tablets per package (NDC 50419-171-03).

Source: Regorafenib (Stivarga) — US FDA prescribing information, 2026-02-09, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.