Pronunciation:

re-goe-RAF-e-nib

Brand Names:

• Stivarga

Dosage Forms:

• Tablet

Warnings:

Severe and sometimes fatal hepatotoxicity has occurred with regorafenib therapy. Monitor hepatic function prior to and during therapy. Adjust dose or interrupt or discontinue therapy if hepatoxicity occurs .

Classifications:

Therapeutic—

Antineoplastic Agent

Pharmacologic—

Tyrosine Kinase Inhibitor

Uses of This Medicine:

Regorafenib is used to treat metastatic cancer (cancer that has spread) of the colon and rectum. It is used in patients who have already been treated with other cancer medicines that did not work well. Regorafenib prevents the growth of tumors.

Regorafenib is also used to treat metastatic gastrointestinal stromal tumors (GIST) in patients who have already received other medicines that did not work well. GIST is a rare cancer that affects the stomach, bowel, or esophagus. This medicine is used to treat a type of liver cancer called hepatocellular cancer (HCC) in patients who have already been treated with sorafenib.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of regorafenib in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of regorafenib in the elderly.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

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

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems or
• Heart disease (eg, heart attack) or
• Hypertension (high blood pressure)—Use with caution. May make these conditions worse.

• Infection—May decrease the body's ability to fight infection.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of This Medicine:

Medicines used to treat cancer are very strong and can have many side effects. Before using this medicine, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with a patient information insert. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Swallow the tablet whole with water. Do not crush, break, or chew it.

Take this medicine at the same time each day with a low-fat meal (less than 30% fat).

Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit products may increase the amount of medicine in your body.

Dosing—

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.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in its original container. Do not place the tablets in daily or weekly pill boxes.

Throw away any unused tablets 7 weeks after opening the bottle for the first time.

Precautions While Using This Medicine:

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.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bleeding gums

bloody or cloudy urine

blurred vision

cough or hoarseness

coughing up blood

difficult, burning, or painful urination

difficulty with breathing or swallowing

dizziness

fever or chills

frequent urge to urinate

headache

increased menstrual flow or vaginal bleeding

lower back or side pain

nervousness

nosebleeds

painful or difficult urination

pounding in the ears

prolonged bleeding from cuts

rash

red or black, tarry stools

redness, swelling, or pain of the skin

scaling of the skin on the hands and feet

slow or fast heartbeats

tingling of the hands and feet

ulcers on the skin

Less common

Chest pain or discomfort

dark-colored urine

general feeling of tiredness or weakness

light-colored stools

nausea or vomiting

pain or discomfort in the arms, jaw, back, or neck

shakiness in the legs, arms, hands, or feet

stomach pain that continues

sweating

yellow eyes or skin

Rare

Blistering, peeling, or loosening of the skin

bloody, black, or tarry stools

chills

confusion

diarrhea

heartburn

indigestion

itching

joint or muscle pain

red skin lesions, often with a purple center

severe stomach pain, cramping, or burning

sore throat

sores, ulcers, or white spots in the mouth or on the lips

trouble breathing

unusual tiredness or weakness

vomiting of material that looks like coffee grounds, severe and continuing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Bad, unusual, or unpleasant taste

hair loss or thinning of the hair

lack or loss of strength

muscle or joint stiffness

weight loss

Less common

Constipation

depressed mood

dry skin and hair

feeling cold

muscle cramps

weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.