Stivarga (Regorafenib) – Oral

Warning:

The Food and Drug Administration (FDA) has issued a boxed warning for Stivarga. Boxed warnings are the agency’s strongest warnings for serious and potentially life-threatening risks.

The boxed warning states:

Severe or life-threatening hepatotoxicity (liver dysfunction) was found in some people who took Stivarga during clinical trials. Liver function tests should be monitored regularly while taking this medication. Stivarga may need to be temporarily or stopped completely depending upon liver function.


What Is Stivarga?

Stivarga (regorafenib) is an orally administered prescription medication that is categorized as a tyrosine kinase inhibitor (TKI).

This drug is used to treat specific types of metastasized colon and rectal cancers, gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (HCC; the most common form of primary liver cancer) in adults 18 and older.

TKI drugs (tyrosine refers to an amino acid) are a subgroup of kinase inhibitors, medications used to block the kinase enzyme. Some kinases are more active in specific types of cancer cells and blocking them can stop cancer cells from multiplying. Kinase inhibitors are often used in the treatment of cancer.

Stivarga works against cancer by stopping the cancer cells from being able to make blood vessels for themselves. It also prevents cancer cells from being able to replicate and continue growing.

The active ingredient in Stivarga, regorafenib, is not available as a generic product. However, the brand-name drug Stivarga is available with a prescription and is administered in the form of an oral tablet.

Drug Facts

Generic Name: Regorafenib

Brand Name(s): Stivarga

Drug Availability: Prescription (specialty pharmacy)

Administration Route: Oral

Therapeutic Classification: Antineoplastic agent

Available Generically: No

Controlled Substance:  N/A

Active Ingredient: Regorafenib

Dosage Form(s): Tablet

What Is Stivarga Used For?

The FDA has approved Stivarga, a TKI, for use in three types of gastrointestinal (GI) cancers for adults 18 years old and older. These cancers include:

Metastatic colorectal cancer (CRC) in people who previously have been treated with:

  • Fluoropyrimidine-based chemotherapy
  • Oxaliplatin-based chemotherapy
  • Irinotecan-based chemotherapy
  • An anti-VEGF (anti-vascular endothelial growth factor) therapy
  • An anti-EGFR (anti-epidermal growth factor receptor) therapy if the cancer is RAS (rat sarcoma virus) wild-type.

Additionally, Stivarga is also used to treat:

  • A locally advanced (cancer that has spread to a nearby lymph node or tissue) GIST
  • An unremovable (a tumor that cannot be removed with surgery) GIST
  • A metastatic (having spread to distant parts of the body) GIST that has been previously treated with imatinib (an oral cancer drug) and sunitinib (an oral cancer drug).

Finally, Stivarga can be used for the treatment of:

  • A diagnosis of HCC that has previously been treated with sorafenib (an oral cancer drug that is used to treat late-stage kidney and liver cancer)

How to Take Stivarga

Stivarga is to be taken for three weeks in a row followed by one week off. It should also be taken after a low-fat meal. The definition of a low-fat meal is a meal that contains 600 calories or less and less than 30% fat.

It should be taken at the same time each day, and the tablets should be swallowed whole with a glass of water. Grapefruit juice and other grapefruit products should be avoided when taking Stivarga.

Also, do not chew or crush the tablets. Your healthcare provider may decrease your dose of Stivarga or advise you to stop taking it for a specific period of time during treatment.

As a result, how long you pause will depend on its efficacy and your specific tolerance.

Storage 

Stivarga should be stored in its original packaging, and should not be placed in any pill packs or pill planners. The pill bottle needs to be closed tightly after opening, and the desiccant package (the insert that keeps the medication dry) should remain in the bottle.

If any tablets remain in the bottle after seven weeks from being opened, they should be discarded appropriately.

Also, do not store Stivarga in the bathroom. Keep the tablets out of the reach of children and pets to prevent accidental consumption.

How Long Does Stivarga Take to Work?

Although the effects of Stivarga may start working in the days and weeks after starting, it can take a few months of therapy to be able to see any improvement in your cancer. Healthcare providers will likely order imaging scans every few months to determine how well Stivarga is working.

What Are the Side Effects of Stivarga?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a medical professional. You may report side effects to the FDA at fda.gov/medwatch or 800-FDA-1088.

Common Side Effects 

There are some side effects that may be experienced when taking Stivarga. 

The most common side effects associated with the use of Stivarga are:

Severe Side Effects 

The FDA has issued a boxed warning for Stivarga. Boxed warnings are the agency’s strongest warnings for serious and potentially life-threatening risks.

The boxed warning states:

Severe or life-threatening hepatotoxicity was found in some people who took Stivarga during clinical trials. Liver function tests should be monitored regularly while taking this medication. Stivarga may need to be temporarily or stopped completely depending upon liver function.

Call your healthcare provider right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you have a medical emergency.

Serious side effects and their symptoms can include the following:

Long-Term Side Effects 

Notably, any of the above mentioned severe side effects hold the potential to become long-term side effects.

Report Side Effects

Stivarga may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Stivarga Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For hepatocellular cancer (HCC):
      • Adults—160 milligrams (mg) (four 40 mg tablets) once a day for 21 days of each 28-day cycle. Your doctor may adjust the dose if needed.
      • Children—Use and dose must be determined by your doctor.
    • For metastatic cancer of the colon or rectum:
      • Adults—160 milligrams (mg) (four 40 mg tablets) once a day for 21 days of each 28-day cycle. Your doctor may adjust the dose if needed.
      • Children—Use and dose must be determined by your doctor.
    • For metastatic gastrointestinal stromal tumors (GIST):
      • Adults—160 milligrams (mg) (four 40 mg tablets) once a day for 21 days of each 28-day cycle. Your doctor may adjust the dose if needed.
      • Children—Use and dose must be determined by your doctor.

Modifications 

In some cases, your healthcare provider may need to adjust the use of your treatment or dosage:

Dose adjustment(s): The dose of Stivarga may need to be modified (changed) if significant side effects develop.

Pregnancy: Based on animal studies and Stivarga's mechanism of action, Stivarga can cause fetal harm when administered to pregnant people. However, there are no available data on Stivarga use in pregnant women. Speak to a healthcare provider if you are currently pregnant or plan on becoming pregnant while taking Stivarga.

Breastfeeding: Because of the potential for serious negative reactions in breastfed infants from Stivarga, do not breastfeed during treatment and for two weeks after the final dose. 

Children: The safety and efficacy of Stivagra in people younger than 18 have not been established.

Adults 65 and older: Of the 1,142 people enrolled in past clinical trials, 40% were 65 and over, while 10% were 75 and over. Per the results of the study, no overall differences in efficacy were observed between older adults versus younger people.

Kidney issues: No dose adjustment is recommended for patients with kidney disease.

Missed Dose

If a dose of Stivarga is missed, it should be skipped. Never double up at the next dosing time to make up for the missed dose.

Overdose: What Happens If I Take Too Much Stivarga?

If you take too much Stivarga, notify your healthcare provider immediately. They may suggest evaluation in the office or the hospital depending upon the dose that was taken.

Although there is no antidote to Stivarga, supportive care measures such as fluids or other medications to treat symptoms may need to be given.

What Happens If I Overdose on Stivarga?

If you think you or someone else may have overdosed on Stivarga, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Stivarga,  call 911 immediately.

Precautions

Drug Content Provided and Reviewed by IBM Micromedex®

If you will be taking this medicine for a long time, it is very important that your doctor check you at regular visits for any problems or unwanted effects that may be caused by this medicine. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Men and women should use an effective form of birth control during treatment and for up to 2 months after treatment. If you think you have become pregnant while using this medicine or within 2 months after the last dose, tell your doctor right away.

Your doctor will check your blood pressure on a regular basis while you are taking this medicine. You may also need to monitor your blood pressure at home. Tell your doctor right away if you have a severe headache, lightheadedness, or changes in your vision.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow skin or eyes. These could be symptoms of a serious liver problem.

This medicine may increase your risk of developing infections. Avoid being near people who are sick or have infections while you are using this medicine. Wash your hands often. Tell your doctor if you have any kind of infection before you start using this medicine. Also tell your doctor if you have ever had an infection that would not go away or an infection that kept coming back.

This medicine may increase your chance of bleeding and cause wounds or injuries to heal more slowly. To help with this problem, stay away from rough sports or situations where you could be bruised, cut, or injured. Brush and floss your teeth gently. Be careful when using sharp objects, including razors and fingernail clippers.

This medicine may cause serious skin problems, including hand-foot skin reaction or a severe rash. Call your doctor right away if you have skin redness, pain, blisters, bleeding, or swelling of the palms of your hands and soles of your feet.

This medicine may cause serious heart problems. Check with your doctor right away if you are having chest pain or discomfort, nausea, pain or discomfort in your arms, jaw, back, or neck, shortness of breath, sweating, or vomiting.

Check with your doctor right away if you have a headache, seizures, confusion, blurred vision or other visual problems. These may be symptoms of a rare and serious brain condition called reversible posterior leukoencephalopathy syndrome (RPLS).

Check with your doctor right away if you have severe burning, cramps, or pain in the stomach area, a high fever, chills, nausea, vomiting, or severe diarrhea. These could be symptoms of a serious stomach or bowel problem.

Make sure any doctor who treats you knows that you are using this medicine. You may need to stop the medicine at least 2 weeks before and after having a surgery.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

What Are Reasons I Shouldn’t Take Stivarga?

Stivarga should not be used in the following types of people:

  • Pregnant or breastfeeding people, as the medication can cause harm to the fetus or infant
  • People who are allergic to regorafenib or any of the other active ingredients in Stivarga

What Other Medications Interact With Stivarga? 

Before starting treatment with Stivarga, tell your healthcare provider about all your medications, including prescription or over-the-counter (OTC) medications, vitamins, and herbal products.

Due to the potential for interactions, the following medications should not be taken along with Stivarga:

Note that this is not a complete list of drug interactions. Consult with your healthcare provider for a complete list.

What Medications Are Similar? 

However, while there are some medications that may work similarly to Stivarga, such as medications that affect blood vessel growth for cancer cells or stop cancer cells from reproducing, there are not any other medications that work in the exact same way as Stivarga.

Frequently Asked Questions

  • What is Stivarga used for?

    Stivarga is used to treat rectum and colon cancer. Stivarga is also used to treat liver cancer and a certain cancer of the digestive system, called GIST.

  • How does Stivarga work?

    Stivarga works by keeping cancer cells from dividing and moving into other areas of the body. It can also keep the cancer cells from being able to make blood vessels for themselves.

  • What are the side effects of Stivarga?

    The most common side effects from Stivarga include:

    • Abdominal pain
    • Nausea
    • Lethargy
    • Sores and irritation to the mouth
    • Decreased appetite
    • Weight loss
  • How to stop taking Stivarga?

    Do not stop taking Stivarga unless instructed by your healthcare team. If you feel like you need to stop taking it due to a side effect or some other issue, notify your healthcare team immediately.

How Can I Stay Healthy While Taking Stivarga?

Take Stivarga as directed by your healthcare provider. Do not stop or change your treatment regimen unless your healthcare provider tells you to.

It is likely that you may experience at least one side effect when taking Stivarga.

Before starting treatment with Stivarga, learn about how to safely take the medication and how to effectively manage any side effects you may experience. Furthermore, don't be afraid of the possibility of needing a reduced dose.

As with all drugs, be sure you tell your healthcare team about all your medications, including prescription or OTC medications, vitamins, and herbal products, before starting the treatment.

Stivarga can interact with other medications, potentially making them less effective or causing unwanted side effects.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Food and Drug Administration. Stivarga (regorafenib) prescribing information.

  2. National Cancer Institute. Kinase inhibitor.

  3. MedlinePlus. Regorafenib.

  4. Food and Drug Administration. Stivarga label.

  5. Prescribers' Digital Reference. Regorafenib - drug summary.

  6. Fan LC, Teng HW, Shiau CW, et al. Regorafenib (Stivarga) pharmacologically targets epithelial-mesenchymal transition in colorectal cancerOncotarget. 2016;7(39):64136-64147. doi:10.18632/oncotarget.11636

By Julie Scott, MSN, ANP-BC, AOCNP
Julie is an Adult Nurse Practitioner with oncology certification and a healthcare freelance writer with an interest in educating patients and the healthcare community.