Regorafenib (Oral)

Regorafenib (Stivarga) is a multi-kinase inhibitor medicine used for the targeted treatment of metastatic colorectal cancers and gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (HCC) cancer.

Overview

Regorafenib was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancers. These are cancers which have spread to the colon or rectum. It is recommended for use after other medicines, such as Oxaliplatin, have failed.

The prescription drug is also used to treat locally, advanced gastrointestinal stromal tumors (GIST). These are rare cancers that have spread to the bowel, stomach or esophagus. It is especially indicated in GIST patients treated with other medicines, such as Imatinib and Sunitinib, that did not work.

In April of 2017, the FDA also approved this chemotherapy medication for treating hepatocellular carcinoma (HCC). This is the most common type of liver cancer but does not spread. It is especially indicated in patients with tumors that stopped responding to treatment with sorafenib, another cancer medicine.

The medicine was produced to block the growth and division of cancer cells by targeting proteins on those cells. If this is successful, it may stop the cancer from spreading further. Patients may feel ill when taking the drug but are encouraged to finish the treatment.

The drug is sold in the US under the brand name, Stivarga. Its use is limited in certain patients due to the risk of serious side effects, including abnormally high blood pressure, severe bleeding, and severe hepatotoxicity. Severe hepatotoxicity, a drug-induced liver injury, has been known to cause death in patients.

Conditions Treated

  • Metastatic colorectal cancers
  • Metastatic gastrointestinal stromal tumors (GIST)
  • Hepatocellular Carcinoma cancer

Type of Medicine

  • Multi-kinase inhibitor

You should consider the potential benefits and risks of using Regorafenib. Your doctor may help you decide if it is safe for you and how to treat you. Routine tests may be done before, during and after your treatment to ensure the medicine is safe for you, and your body's response to it.

Liver function tests are necessary because severe, even fatal hepatotoxicity (drug-induced liver injury) has occurred in patients treated with this drug. Blood tests and screenings may also be done to determine whether you are at risk for other types of cancers or medical problems.

Tell your doctor if you are allergic to the medicine or have had an unusual reaction to it. Some patients may also be allergic to inactive ingredients in the medication. In discussing allergies, tell your doctor about any allergy to foods, preservatives, dyes or animals you may have.

Also tell your doctor if you are breastfeeding, or you (or your partner) are pregnant, may be pregnant or plan to become pregnant so you can be advised of the necessary precautions.

Certain medications or medical conditions may affect the way the tablet works. Tell your doctor if you have any other medical problems, and of all medications you are taking or plan to take. These include prescription and over-the-counter medicines (OTC's), vitamins, nutritional supplements, and herbal products.

Side Effects

Side effects are expected with the use of most, if not all, medicines. Some of them may be severe or serious and require urgent medical attention. Others may be mild and may go away on their own.

Severe hepatotoxicity, which can be fatal, is one of the most serious side effects that occurred in patients being treated with Regorafenib. Hemorrhage and gastrointestinal perforation (holes in the intestines) are other serious adverse effects which require emergency medical care.

When to call your doctor right away

When using Regorafenib, call your doctor immediately if you experience the following symptoms. They may be signs of a serious medical problem:

  • Blood pressure problem: lightheadedness, change in vision, or severe headaches.
  • Serious heart problem: shortness of breath, discomfort or pain in the chest, nausea or vomiting, sweating, or discomfort or pain the neck, jaw, back or arms.
  • Serious skin problem: hand-foot skin reactions, swelling of the palms of your hands, swelling of the soles of your feet, blisters, redness, pain or blistering of the skin, or severe skin rash.
  • Serious liver problem: dark urine, yellowing of the skin or eyes, tenderness or pain in the upper stomach, pale color stool, nausea, loss of appetite or vomiting.
  • Serious brain condition (reversible posterior leukoencephalopathy syndrome (RPLS)): blurred vision, headache, confusion or seizures.
  • Serious bowel or stomach problem: high fever, nausea, severe cramps, pain or burning in the stomach, vomiting or severe diarrhea.

Tell your doctor immediately if any of the following other side effects occur:

More commonly occur:

  • Headache
  • Dizziness
  • Blurred vision
  • Difficulty breathing or swallowing
  • Increase in menstrual flow
  • Nervousness
  • Nosebleeds
  • Bleeding gums
  • Cough
  • Coughing up blood
  • Hoarseness
  • Vaginal bleeding that is not menstrual
  • Pain on urination
  • Difficulty urinating
  • Cuts or bruises that take longer than usual to heal
  • Rash
  • Skin ulcers
  • Pain, swelling or redness of the skin
  • Scaling of the skin on the hands and feet
  • Heartbeats that are too fast or too slow
  • Feeling of pounding in the ears
  • Tingling hands and feet
  • Pain in the back or lower side
  • Fever (with or without chills)
  • Stool that is black, red or tarry

Because the medication may increase the risk of bleeding and slow the healing of wounds, you should reduce the chance for cuts, bruises or other injuries to yourself. Take extra care to brush and floss gently to avoid bruising the gum.

Less commonly occur:

  • Feeling of weakness or tiredness
  • Urine dark in color
  • Stools light in color
  • Nausea or vomiting
  • Discomfort or pain in the chest
  • Unusual sweating
  • Shaking of the legs, feet, arms or hands
  • Stomach pain that does not go away
  • Yellow eyes or skin
  • Discomfort or pain in the neck, jaw, back or arms

Rarely occur:

  • Heartburn
  • Burning, cramping or pain in the stomach (severe)
  • Vomit that looks like coffee grounds
  • Confusion
  • Indigestion

The following side effects may not require medical attention if they occur. They tend to go away on their own. Talk to your doctor if they become bothersome, worse or do not go away.

More commonly occur:

  • Thinning or loss of hair
  • Stiffness in the joints or muscles
  • Unusual or unpleasant taste in the mouth
  • Unexplained weight loss
  • Lack or loss of strength

Less commonly occur:

  • Feeling depressed
  • Dryness of the skin or hair
  • Unexplained weight gain
  • Feeling cold
  • Constipation
  • Muscle cramps

Some patients may experience other side effects not listed in this guide. All of the listed side effects may not occur in one single patient. Tell your doctor if you notice other unusual symptoms. You can ask your doctor or healthcare professional what to do to reduce or prevent side effects. You may call the FDA at 1-800-FDA-1088 to report side effects.

Dosage

Medicine dosage may vary from patient to patient. It may depend on age, weight, the condition being treated, the use of other medicines, and the presence of other medical problems.

When taking your dose, carefully follow all directions given to you on the prescription label and by your doctor or pharmacist. These directions may include the amount of your dose, the strength of it, how often you take it, the time between each dose, and the duration of your treatment.

The medication is supplied as a 40 milligrams (mg) oral tablet. You should take your dose with a glass of water (avoid grapefruit juice), right after a low-fat meal. The recommended dose is the same for adults with the following conditions:

  • Cancers that have spread to the colon or rectum
  • Gastrointestinal stromal tumors (GIST) that have spread to the stomach, esophagus or bowel
  • Hepatocellular Carcinoma (HCC) cancer

Adults: After a low-fat meal, take 160 milligrams (mg) (four 40 mg tablets) once a day for 21 days of each 28-day cycle. Your doctor may adjust your dose if necessary.

Children: Not indicated in children. Treatment must be determined by a doctor.

Missed dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is time to take the next dose, skip the missed dose and take the next dose as scheduled. Continue with your regular dosing schedule.

Overdose

Call your local poison control center at 1-800-222-1222 if you overdose on this drug. If the patient collapses or is not breathing, call 911.

Interactions

Using certain medications together with Regorafenib is not recommended, but may be required in some cases for the health of the patient. In such cases, your doctor may take the necessary precautions to ensure all your medicines are safely used.

The following medications were listed because they have the potential to cause significant interaction with Regorafenib. If any of them is prescribed together with your cancer treatment, your doctor may change the dose or how often you use all your medicines.

  • Telithromycin
  • Boceprevir
  • Bupropion
  • Fosphenytoin
  • Lumacaftor
  • Ceritinib
  • Clozapine
  • Piperaquine
  • Cobicistat
  • Conivaptan
  • Mitotane
  • Doxorubicin
  • Eliglustat
  • Idelalisib
  • Amiodarone
  • Indinavir
  • Cilostazol
  • Itraconazole
  • St. John's Wort
  • Clarithromycin
  • Ketoconazole
  • Lopinavir
  • Nefazodone
  • Ritonavir
  • Nelfinavir
  • Ospemifene
  • Phenytoin
  • Carbamazepine
  • Posaconazole
  • Dasabuvir
  • Rifapentine
  • Warfarin
  • Saquinavir
  • Doxorubicin Hydrochloride Liposome
  • Telaprevir
  • Voriconazole
  • Enzalutamide
  • Rifampin

Other Interactions

Food, tobacco or alcohol

To avoid adverse interaction, your doctor, pharmacist or healthcare professional may tell you if you should avoid certain foods, alcohol or tobacco.

The following food is not recommended to be used with your medication. If it is necessary to use it, your doctor may give you directions on how or when to do so:

  • Grapefruit juice

Other medical problems

The existence of other medical conditions may affect the use of this chemotherapy drug. To avoid worsening their condition, the drug should be used with caution in patients who have the following medical problems:

  • High blood pressure (Hypertension);
  • Heart disease (or have had a heart attack); or
  • Bleeding problems.

The medicine should also be used with caution in patients with the following condition. The side effects of the drug may increase because the medicine takes a longer time to leave the body:

  • Liver disease

Warnings

  • Do not take Regorafenib if you are allergic to it or any of its inactive ingredients.
  • Do not use this drug if you are pregnant, may be pregnant or plan to become pregnant. The medication may harm an unborn baby. Your doctor may give you advice on necessary precautions you can take. You should also avoid becoming pregnant during treatment, and at least two months after.
  • If you are a male patient, you should prevent pregnancy during treatment, and at least two months after. Both male and female patients and their partners should use contraceptives to prevent pregnancy during this period.
  • Do not use this medicine if you are breastfeeding to avoid any risk to your breastfeeding infant. Your doctor must determine if to treat you and what your dose should be.
  • You should not use the drug if you are an elderly patient, unless your doctor approves of it and determines a dose that is right for you. Geriatric patients are more likely to experience more side effects due to their age
  • Avoid having surgery or a medical procedure without first telling your doctor or the person performing the procedure that you are taking Regorafenib.
  • Do not take this treatment if you have certain medical conditions, especially those that can increase the risk of severe liver damage (hepatotoxicity) or holes in the intestines.
  • Do not stop using your medication, even if you feel ill while taking it, unless your doctor tells you to.
  • You must not share your medicine with anyone else, even if they have similar symptoms.
  • Do not take your medicine with grapefruit juice. It can cause an adverse interaction with the drug.
  • Keep all your follow-up appointments so your doctor can determine if it is safe to continue treatment.

Storage

Store the medicine, in a closed container, at room temperature. Keep away from moisture, heat, and direct light.
Keep from freezing and out of the reach of children.

Throw away the medicine once it expires or is no longer needed. Throw it away if it has been unused for seven weeks after first opening the bottle.

You may ask your doctor, healthcare professional or local waste disposal company how to safely dispose of unused or expired medication.

Summary

Regorafenib (Stivarga) is a multi-kinase inhibitor medication that treats cancers that have spread to the colon or rectum, and gastrointestinal stromal tumors (GIST) which have spread to the stomach, esophagus, and bowel.

It has been so effective in treating these cancers that, in April 2017, the FDA approved it for the treatment of hepatocellular Carcinoma (HCC), a common type of liver cancer.

However, the use of this medication is more of an alternative treatment. It is recommended for treating these conditions only after other drugs have failed.

Regorafenib is not recommended for use in patients with certain medical conditions due to the risk of serious adverse effects. Severe hepatotoxicity, which can be fatal, is one of the most serious adverse effects that occurred in patients being treated with it.

It should also not be used in patients who are pregnant, may be pregnant or plan to become pregnant. Because of the risk of harm to an unborn baby, both male and female patients and their partners are encouraged to use contraceptives.

Although it is common for patients to feel ill when taking Regorafenib, they are encouraged to complete the course of treatment with the medicine.

A list of side effects may occur during treatment, and some are serious enough to require emergency medical attention. In addition, taking this chemotherapy drug with other medications can increase the risk of adverse interaction.

Doctor's caution is required when deciding use and dosage of all other medicines prescribed while taking Regorafenib. This is to ensure that treatment is carried out in a manner that protects the patient's health.

 

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Last Reviewed:
January 31, 2018
Last Updated:
April 05, 2018
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