+ -Text Size



Trade/other name(s): Stivarga

Why would this drug be used?

This drug is used to treat colorectal cancer and gastrointestinal stromal tumor. It is also being studied for use against other types of cancer.

How does this drug work?

Regorafenib is a type of targeted therapy known as a kinase inhibitor. Kinases are proteins on or near the surface of a cell that transmit (send) important signals to the cell’s control center. Regorafenib inhibits many different kinase proteins. Some of these kinases in tumor cells would normally help the cells grow. Other kinases would normally help form new blood vessels (angiogenesis) that could feed a growing tumor. By blocking these proteins, regorafenib may help stop the growth of tumors.

Before taking this medicine

Tell your doctor…

  • If you are allergic to anything, including medicines, dyes, additives, or foods.
  • If you have any type of liver disease (including hepatitis). This drug can cause liver damage, which in some people can be serious or even fatal. Your doctor will do blood tests to check your liver function before and during treatment.
  • If you have a history of high blood pressure. This drug might raise blood pressure. Your blood pressure should be well controlled before starting this drug, and your doctor will monitor it closely during treatment.
  • If you have a history of chest pain, heart attacks, or other heart problems. This drug can affect blood flow to the heart and increase your risk of heart attacks.
  • If you have a history of any bleeding problems, such as coughing up blood or having blood in your urine or stools. This drug may make bleeding worse, which in some cases may be life threatening.
  • If you have a wound that is not healed or are planning to have surgery soon. This drug may affect wound healing, so it should be stopped at least 2 weeks before any surgery.
  • If you have any other medical conditions such as kidney disease, diabetes, gout, or infections. These conditions may require more careful monitoring by your doctor.
  • If you are pregnant, trying to get pregnant, or if there is any chance of pregnancy. This drug can cause problems with the fetus if taken at the time of conception or during pregnancy (see “Precautions” below).
  • If you are breastfeeding. While no studies have been done, this drug may pass into breast milk and affect the baby. Breastfeeding is not recommended during treatment with this drug.
  • If you think you might want to have children in the future. This drug might affect fertility. Talk with your doctor about the possible risk with this drug.
  • About any other prescription or over-the-counter medicines or supplements you are taking, including vitamins and herbs. In fact, keeping a written list of each of these medicines (including the doses of each and when you take them) with you in case of emergency may help prevent complications if you get sick.

Interactions with other drugs

Regorafenib can interact with a number of drugs and supplements, so it is very important to check with your health care team before taking any new medicines.

Some drugs and supplements can lower the levels of regorafenib in the blood, which might make it less effective:

  • Anti-seizure drugs, such as carbamazepine (Tegretol), phenobarbital (Solfoton), and phenytoin (Dilantin)
  • Drugs to treat tuberculosis (TB), such as rifampin (Rifadin, Rimactane; also Rifamate and Rifater), rifabutin (Mycobutin), and rifapentin (Prifin)
  • The steroid drug dexamethasone (Decadron)
  • St. John’s wort (an herbal dietary supplement)

Some drugs and supplements could cause regorafenib to build up in your blood, which might worsen side effects and other problems:

  • Some antibiotics, such as erythromycin, clarithromycin (Biaxin), telithromycin (Ketek), and similar drugs
  • Some anti-fungal medicines, such as ketoconazole (Nizoral), itraconazole (Sporanox), posaconazole (Noxafil), and voriconazole (Vfend)
  • Some anti-depressant drugs, such as nefazodone (Serzone)
  • Some anti-HIV drugs, such as indinavir (Crixivan), ritonavir (Kaletra), nelfinavir (Viracept), atazanavir (Reyataz), saquinavir (Invirase), and others

These drugs should be avoided while taking regorafenib if possible. Do not start or stop taking any of these medicines while taking regorafenib without talking with your doctor(s) about all of the medicines you take, including regorafenib.

Drugs or supplements that interfere with blood clotting might raise the risk of bleeding during treatment with regorafenib. These include:

  • Vitamin E
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and many others
  • Warfarin (Coumadin)
  • Ticlopidine (Ticlid)
  • Clopidogrel (Plavix)

Note that many cold, flu, fever, and headache remedies contain aspirin or ibuprofen. Ask your doctor or pharmacist before taking any of these medicines.

Other medicines or supplements may affect blood levels of regorafenib, or levels of these drugs may be affected by taking regorafenib. Make sure your doctor knows all of the drugs and supplements you are taking.

Check with your doctor, nurse, or pharmacist about any other medicines, herbs, and supplements you are taking, and whether alcohol can cause problems with this medicine.

Interactions with foods

This drug should be taken with food (see the next section).

Grapefruit, grapefruit juice, or grapefruit extract may affect the amount of regorafenib in your body. You should avoid grapefruit products while taking this drug. Check with your doctor, nurse, or pharmacist about whether any other specific foods could be a problem.

Tell all the doctors, dentists, nurses, and pharmacists you visit that you are taking this drug.

How is this drug taken or given?

Regorafenib is taken by mouth as 40 milligram (mg) tablets. The usual starting dose is 160 mg (4 tablets), once a day for 21 days (3 weeks), followed by 7 days (1 week) off. The cycle is then repeated.

The tablets should be taken at the same time each day with a low-fat breakfast. They should be swallowed whole (not chewed or crushed). Examples of a low-fat breakfast include:

  • 2 slices of white toast with 1 tablespoon of low-fat margarine and 1 tablespoon of jelly, and 8 ounces of skim milk
  • 1 cup of cereal, 8 ounces of skim milk, 1 slice of toast with jelly, apple juice, and 1 cup of coffee or tea

Your doctor may need to lower your dose or delay or stop your treatment if you have side effects.

Take this drug exactly as directed by your doctor. If you do not understand the instructions, ask your doctor or nurse to explain them to you.

Keep this medicine in the bottle that it comes in – do not put the tablets in a weekly or monthly pill box. Keep the desiccant (the little packet that comes with the pills) in the bottle as well. Store the bottle at room temperature, away from heat and moisture and out of the reach of children and pets.


This drug may interact with a number of other drugs or supplements in the body. (See “Interactions with other drugs”) Be sure your doctor is aware of all drugs and supplements you are taking. Do not start or stop taking any drug without talking to your doctor about all of them.

This drug may cause liver damage, which in some cases can be serious or even fatal. Liver damage may show first up as abnormal results on blood tests. This drug should not be used in patients with severe liver problems. Your doctor will order blood tests and will check you for signs of liver problems before and during treatment to make sure your liver is working well. The dose of this drug may need to be lowered or the drug stopped altogether if tests show your liver is not functioning normally. Tell your doctor or nurse right away if you have yellowing of the skin or the whites of your eyes (jaundice), dark urine, nausea or vomiting, loss of appetite, pain on the right side of your belly, or any abnormal bruising or bleeding.

This drug can cause problems with bleeding from the stomach, intestines, lungs, and other parts of the body, which in some cases may be fatal. Talk with your doctor before taking any drugs or supplements that might affect your body’s ability to stop bleeding (see “Interactions with other drugs”). Tell your doctor right away if you have unusual bruising or bleeding such as nosebleeds, bleeding gums, coughing or vomiting up blood, heavier than normal menstrual bleeding, blood in your urine, or black, tarry stools.

Regorafenib can cause high blood pressure, which in rare cases can be life threatening. Patients should have normal blood pressure before starting this drug, and blood pressure should be checked regularly while the patient is taking regorafenib. Patients being treated for high blood pressure can take this drug, as long as their blood pressure is controlled (normal) by medicine. Tell your doctor right away if you have severe headaches, feel dizzy or lightheaded, or if you have changes in your vision.

This drug can cause a condition known as hand-foot syndrome, in which a person may have pain, numbness, tingling, redness, or swelling in the hands or feet. When severe, this can cause peeling, blistering, or open sores on the skin in these areas. This drug can also cause skin rash. Let your doctor know right away if you notice any of these symptoms.

Regorafenib can decrease blood flow to the heart and increase the risk of heart attacks. Patients who are already at high risk for these problems should use this drug with caution. Call your doctor right away if you have chest pain, jaw or arm pain, or shortness of breath, or if you feel dizzy or lightheaded.

This drug can cause problems with wound healing and should be stopped at least 2 weeks before any planned surgery.

Rarely, regorafenib can cause holes (perforations) in or abnormal connections (fistulas) between parts of the digestive tract, which can be life-threatening. Tell your doctor or nurse right away if you are vomiting blood or if you have severe stomach (abdominal) pain, fever, swelling in the abdomen, or red or very dark colored stools.

In rare cases, this drug may affect the brain, causing what is known as reversible posterior leukoencephalopathy syndrome (RPLS). Symptoms of RPLS might include seizures, headache, trouble thinking, confusion, changes in vision, or other problems. Tell your doctor right away if you notice any of these symptoms.

Avoid pregnancy while taking this drug. It might harm the fetus. Women who could become pregnant and men who are taking this drug should use an effective form of birth control during treatment with this drug and for at least 2 months after they stop taking it. Check with your doctor about what kinds of birth control can be used with this medicine. Tell your doctor right away if you or your partner becomes pregnant during treatment or within 2 months of stopping treatment.

Possible side effects

You will probably not have most of the following side effects, but if you have any talk to your doctor or nurse. They can help you understand the side effects and cope with them.


  • Feeling tired or weak
  • Fever
  • Loss of appetite
  • Sores in the mouth or throat
  • Diarrhea
  • Weight loss
  • Infection
  • Hand-foot syndrome (redness and pain in the palms of the hands and the soles of the feet)*
  • Rash*
  • High blood pressure*
  • Bleeding, which in some cases may be severe*
  • Voice changes or hoarseness
  • Low blood cell counts (can increase the risk of fatigue, infections, and bleeding)
  • Abnormal blood tests suggesting drug may be affecting the liver (Your doctor will discuss the importance of this finding, if any.)*
  • Low levels of minerals in the blood
  • Protein in the urine (a possible sign of kidney damage)

Less common

  • Headache
  • Hair loss
  • Change in how things taste
  • Muscle or joint stiffness


  • Dry mouth
  • Hypothyroidism (can cause fatigue, weight gain, feeling cold, or constipation)
  • Tremor
  • Gastroesophageal reflux (can cause heartburn)
  • Severe liver damage*
  • Heart attack*
  • Vision loss*
  • Hole (perforation) or abnormal connection (fistula) in the stomach or intestines*
  • Changes in the brain that can cause headache, confusion, seizures, or blindness*
  • Death from bleeding, severe liver damage, or other problems

*See the “Precautions” section for more detailed information.

Other side effects not listed above can also occur in some patients. Tell your doctor or nurse if you develop these or any other problems.

FDA approval

Yes – first approved in 2012

Disclaimer: This information does not cover all possible uses, actions, precautions, side effects, or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for talking with your doctor, who is familiar with your medical needs.

Last Medical Review: 10/09/2012
Last Revised: 02/26/2013