Reviewed on 5/5/2022

What Is Regorafenib and How Does It Work?

Regorafenib is a prescription medicine used to treat the symptoms of colorectal cancer (CRC), gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (HCC).

  • Regorafenib is available under the following different brand names: Stivarga

What Are Dosages of Regorafenib?

Adult dosage


  • 40mg

Colorectal Cancer

Adult dosage

  • 160 mg (four 40-mg tablets) orally once daily for the first 21 days of each 28-day cycle
  • Continue treatment until disease progression or unacceptable toxicity

Gastrointestinal Stromal Tumors

Adult dosage

  • 160 mg (four 40-mg tablets) orally once daily for the first 21 days of each 28-day cycle
  • Continue treatment until disease progression or unacceptable toxicity

Hepatocellular Carcinoma

Adult dosage

  • 160 mg (four 40-mg tablets) orally once daily for the first 21 days of each 28-day cycle
  • Continue treatment until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Are Side Effects Associated with Using Regorafenib?

Common side effects of Regorafenib include:

  • diarrhea,
  • nausea,
  • stomach pain,
  • loss of appetite,
  • weight loss,
  • increased blood pressure,
  • fever,
  • infection,
  • abnormal liver function test,
  • pain or redness in the mouth or throat,
  • hoarse voice,
  • weakness, and
  • tiredness.

Serious side effects of Regorafenib include:

  • hives,
  • difficulty breathing,
  • swelling of the face, lips, tongue, or throat,
  • fever,
  • sore throat,
  • burning eyes,
  • skin pain,
  • red or purple skin rash with blistering and peeling,
  • nausea,
  • vomiting,
  • sleep problems,
  • dark urine,
  • yellowing of the skin or eyes (jaundice),
  • confusion,
  • change in mental status,
  • vision,
  • seizure,
  • pain, blisters, bleeding, or severe rash in the palms of the hands or the soles of feet,
  • chest pain,
  • shortness of breath,
  • lightheadedness,
  • severe headache,
  • blurred vision,
  • pounding in the neck or ears,
  • chills,
  • severe stomach pain or swelling,
  • increase thirst,
  • decreased urination,
  • bruising,
  • nosebleeds,
  • heavy menstrual periods,
  • blood in urine,
  • bloody or tarry stools,
  • coughing up blood,
  • bleeding that will not stop,
  • cough with or without mucus,
  • vaginal itching,
  • vaginal discharge,
  • pain or burning when urinating, and
  • redness and swelling.

Rare side effects of Regorafenib include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Regorafenib?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Regorafenib has severe interactions with at least 40 other drugs.
  • Regorafenib has serious interactions with the following drugs:
  • Regorafenib has moderate interactions with at least 53 other drugs.
  • Regorafenib has minor interactions with no other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Regorafenib?


  • None

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Regorafenib?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Regorafenib?”


  • Also, see Dosage Modifications
  • May cause severe drug-induced liver injury with fatal outcome (see Black Box Warnings); obtain liver function tests (ALT, AST, and bilirubin) before initiation of therapy and monitor at least every 2 weeks during the first 2 months of treatment; thereafter, monitor monthly or more frequently as clinically indicated; monitor liver function tests weekly in patients experiencing elevated liver function tests until improvement to less than 3 times the ULN or baseline; temporarily hold and then reduce or permanently discontinue therapy depending on severity and persistence of hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis
  • Increases risk for hemorrhage; discontinue therapy for severe or life-threatening hemorrhage
  • Increased risk of infections reported; most common infections include urinary tract infections, nasopharyngitis, mucocutaneous and systemic fungal infections, and pneumonia
  • Increases risk for HFSR/PPES and rash; a higher incidence of HFSR reported in Asian patients; interrupt and then reduce or discontinue regorafenib depending on severity and persistence of dermatologic toxicity
  • Hypertension may occur, typically during the first treatment cycle; do not initiate therapy unless blood pressure is adequately controlled; monitor blood pressure weekly for the first 6 weeks of treatment and then every cycle, or more frequently, as clinically indicated; temporarily or permanently withhold therapy for severe or uncontrolled hypertension
  • Myocardial ischemia and infarction observed in clinical trials; withhold regorafenib for new or acute cardiac ischemia/infarction and resume only after resolution of acute ischemic events
  • One case report of reversible posterior leukoencephalopathy syndrome (RPLS) reported (1 of 1100 treated patients); discontinue therapy if RPLS occurs
  • Discontinue therapy if gastrointestinal perforation or fistula occur
  • May impair wound healing (class effect of VEGFR inhibitors); complications can occur in patients who receive drugs that inhibit the VEGF signaling pathway; discontinue at least 2 weeks before scheduled surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing; safety of resumption of the drug after resolution of wound healing complications not established; discontinue therapy in patients with wound dehiscence
  • Embryo-fetal toxicity is likely if taken while pregnant (see Pregnancy & Lactation)
  • Drug interactions overview
    • Strong CYP3A4 inhibitors
      • Coadministration with strong CYP3A4 inhibitors increases regorafenib plasma concentrations, decreased active metabolite (M-2 and M-5) plasma concentrations, and may increase toxicity
      • Avoid concomitant use of regorafenib with strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole)
    • Breast cancer resistance protein (BCRP) substrates
      • Coadministration with a BCRP substrate increases the BCRP substrate plasma concentrations
      • Closely monitor for signs and symptoms of exposure-related toxicity of the BCRP substrate (eg, methotrexate, fluvastatin, atorvastatin)
      • Consult the concomitant BCRP substrate product information when considering the administration of Regorafenib
      • UGT substrates
      • Regorafenib competitively inhibits UGT1A9 and UGT1A1 substrates

Pregnancy and Lactation

  • Based on animal studies and mechanism of action, fetal harm may occur when administered to a pregnant woman
  • There are no available data on use in pregnant women
  • Advise pregnant women of the potential hazard to a fetus
  • Contraception
    • Females: Use effective contraception during treatment and for 2 months following the final dose
    • Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 2 months following the final dose
  • Infertility
    • There are no data on the effect on human fertility
    • Results from animal studies indicate that regorafenib can impair male and female fertility
  • Lactation
    • There are no data on the presence of regorafenib or its metabolites in human milk, the effects of regorafenib on the breastfed infant, or milk production In rats, regorafenib and its metabolites are excreted in milk
    • Because of the potential for serious adverse reactions in breastfed infants from regorafenib, do not breastfeed during treatment and for 2 weeks after the final dose
Medscape. Regorafenib.

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