Sunitinib

(sue-nit-in-nib)

Trade/other name(s): Sutent, SU11248, sunitinib malate

Why would this drug be used?

This drug is used to treat advanced kidney cancer, gastrointestinal stromal tumor (GIST), and pancreatic neuroendocrine tumors. It is also being studied for use against a number of other cancers.

How does this drug work?

Sunitinib is a type of targeted therapy known as a tyrosine kinase inhibitor. Tyrosine kinases are proteins at the surface of a cell that signal the cell's control center to grow and divide or help form new blood vessels (angiogenesis) to feed the tumor. By blocking these proteins, sunitinib can help stop the growth of cancer cells.

Before taking this medicine

Tell your doctor…

• If you are allergic to anything, including medicines, dyes, additives, or foods.
• If you have high blood pressure. Sunitinib may raise blood pressure. Your doctor will likely want to monitor this closely during treatment.
• If you have any type of liver disease (including hepatitis). This drug is cleared from the body mainly by the liver. Reduced liver function might result in more drug than expected staying in the body, which could lead to unwanted side effects. Your doctor may need to adjust your dose accordingly.
• If you have ever been diagnosed with heart disease, including heart attack, long Q-T syndrome, heart rhythm problems, or very slow heart rate. Sunitinib may weaken the heart muscle and cause other heart problems, especially in people known to have heart disease.
• If you have any other medical conditions such as kidney disease, congestive heart failure, bleeding problems, seizures, diabetes, gout, or infections. These conditions may require that your medicine dose, regimen, or timing be changed.
• 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. Check with your doctor about what kinds of birth control can be used with this medicine. In pregnant women, treatment with this drug should be used only if the potential benefit to the mother outweighs the risk to the fetus.
• If you are breast-feeding. While no studies have been done, this drug may pass into breast milk and affect the baby. Breast-feeding is not recommended during treatment with this drug.
• If you think you might want to have children in the future. This drug may affect fertility. Talk with your doctor about the possible risk with this drug and the options that may preserve your ability to have children.
• About any other prescription or over-the-counter medicines 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

Sunitinib can interact with a number of drugs and supplements. The following drugs can also cause sunitinib to build up in the body, raising the risk of serious side effects:

• the antidepressant nefazodone (Serzone)
• the antibiotics erythromycin (EES), clarithromycin (Biaxin) and telithromycin (Ketek)
• anti-fungals such as ketoconazole (Nizoral), itraconazole (Sporanox), voriconazole (Vfend)
• HIV drugs such as indinavir, ritonavir, saquinavir, nelfinavir, atazanavir, and others

Do not start or stop taking these medicines while on sunitinib without talking with the prescribing doctor(s) about all of the medicines you take, including sunitinib.

These drugs and supplements can lower the levels of sunitinib in the blood and make it less effective:

• anti-seizure drugs carbamazepine (Tegretol), phenobarbital (Luminal), and phenytoin (Dilantin)
• TB drugs rifampin (Rifadin, Rimactane; also in Rifamate and Rifater), rifapentin (Priftin), and rifabutin (Mycobutin)
• the steroid drug dexamethasone (Decadron)
• St. John's wort (herbal dietary supplement)

If you need to take these drugs, your doctor may need to adjust your dose of sunitinib.

Drugs that affect the heart rhythm such as amiodarone (Cordarone), disopyramide (Norpace), dofetilide (Tikosyn), flecainide (Tambocor), mexiletine (Mexitil), moricizine (Ethmozine), procainamide (Procanbid, Pronestyl), propafenone (Rythmol), quinidine (Quinidex), sotalol (Betapace, Betapace AF), and tocainide (Tonocard) may increase the risk of harmful effects on the heart.

Any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with sunitinib. These include:

• vitamin E
• non-steroidal 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 pharmacist if you aren't sure what's in the medicines you take.

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

Avoid grapefruit or grapefruit juice, because it may change the level of sunitinib in your blood. Check with your doctor, nurse, or pharmacist about whether other foods may 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?

Sunitinib comes in 12.5, 25, and 50 mg capsules. Swallow the capsules whole, with or without food. Do not split, chew, crush, or melt capsules. The recommended starting dose is 50 mg once a day for 4 weeks, followed by 2 weeks of rest when the drug isn't taken. This schedule may need to be adjusted if you have side effects. Do not drink grapefruit juice or eat grapefruit until you stop taking the drug entirely.

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 the medicine in a tightly closed container away from heat and moisture and out of the reach of children and pets.

Precautions

This drug may interact with a number of other drugs or supplements in the body -- see "Interactions" above. 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 the drugs you are taking.

Sunitinib may raise your blood pressure. Tell your doctor if you have ever had high blood pressure or are taking medicines for it. Your blood pressure should be checked regularly during treatment.

Sunitinib may weaken the muscles of the heart, which in some cases may lead to congestive heart failure. In rare cases, it may also cause other serious heart problems, including changes in the heart's rhythm. Tell your doctor if you have ever been diagnosed with heart disease. Your doctor may want to test your heart before you start treatment. Report any episodes of chest pain, extreme tiredness, lightheadedness, gasping for air, shortness of breath, or swelling in the hands or feet to your doctor right away.

This drug may cause diarrhea. If left unchecked, this could lead to dehydration and chemical imbalances in the body. Your doctor will likely prescribe medicine to help prevent or control this side effect. It is very important that you take this medicine as prescribed. Make sure you get the medicine right away, so that you will have it at home when you need it. Let your doctor know if the medicine does not control the diarrhea.

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. Peeling, blistering, or sores on the skin in these areas are also possible. Let your doctor know right away if you notice any of these symptoms.

Rarely this drug can cause a syndrome of seizures, headache, high blood pressure, confusion or change in mental status, and loss of vision. Call your doctor if you have any of these symptoms.

This drug may lower your platelet count in the weeks after it is given, which can also increase your risk of bleeding. Speak with your doctor before taking any drugs or supplements that might affect your body's ability to stop bleeding, such as aspirin or aspirin-containing medicines, warfarin (Coumadin), or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools..

Your doctor will likely test your blood throughout your treatment, looking for effects of the drug on blood counts or on blood chemistry levels. Based on the test results, you may be given medicines to help treat any effects. Your doctor may also need to reduce or delay your next dose of this drug, or even stop it completely. Be sure to keep all your appointments for lab tests and doctor visits.

This drug can lower your white blood cell count, especially in the weeks after the drug is given. This can increase your chance of getting an infection. Be sure to let your doctor or nurse know right away if you have any signs of infection, such as fever (100.5° or higher), chills, pain when passing urine, new onset of cough, or bringing up sputum.

Do not get any immunizations (vaccines), either during or after treatment with this drug, without your doctor's OK. Sunitinib may affect your immune system. This could make vaccinations ineffective, or even lead to serious infections if you get a live virus vaccine during or soon after treatment. Try to avoid contact with people who have recently received a live virus vaccine, such as the oral polio vaccine or smallpox vaccine. Check with your doctor about this.

Tell your doctor if you have surgery planned. This drug can keep wounds from healing as they should. Your doctor may want to stop this medicine for some time before surgery.

Avoid pregnancy during and for some time after taking this drug. Talk with your doctor about this.

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.

Common

• low white blood cell count (with increased risk of infection) *
• diarrhea*
• upset stomach
• nausea/vomiting
• mouth sores
• loss of appetite
• feeling tired
• yellowing of the skin

Less common

• high blood pressure*
• bleeding, including nosebleeds, bleeding in the brain or bowel*
• redness, pain, swelling, or blisters on hands or feet (hand-foot syndrome)*
• low blood platelet count with increased risk for bleeding*
• constipation
• rash
• dry skin
• altered taste
• joint pain
• abdominal pain
• shortness of breath*
• cough
• feeling weak
• headache
• fever
• swelling in the hands or feet*
• abnormal blood tests suggesting drug may be affecting the liver, kidneys, or pancreas (Your doctor will discuss the importance of this finding, if any.)

Rare

• hair loss
• heart attacks*
• congestive heart failure with symptoms like rapid weight gain, trouble breathing, and swelling of hands or feet, which may get better after the drug is stopped
• major blood clots (in the legs, lungs, or brain)
• low thyroid function (hypothyroidism) or high thyroid levels (hyperthyroidism)
• severe allergic reaction with symptoms like itching, hives, swelling in the mouth or throat, trouble breathing or swallowing, and shock
• death due to heart failure, bleeding, infection, blood clot in the lung, or kidney failure

*See the "Precautions" section for more detailed information.

There are other side effects not listed above that 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 2006.

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.