Imatinib

(im-mat-uh-nib)
Trade/other name(s): Gleevec, Glivec, STI 571, STI-571, imatinib mesylate

Why would this drug be used?

This drug is used to treat some types of leukemia, especially chronic myelogenous leukemia (CML) and certain types of adult acute lymphocytic leukemia (ALL). It is also used for gastrointestinal stromal tumors (GISTs). It is used to treat a number of other cancers and non-cancerous conditions as well.

How does this drug work?

Imatinib is a type of targeted therapy known as a tyrosine kinase inhibitor. Its targets include tyrosine kinase proteins. These abnormal proteins are found at the surface of certain cancer cells. They send constant signals telling the cells to divide and stay alive. By blocking these signals, imatinib can stop the cells from growing and cause them to die.

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 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 congestive heart failure or other heart problems. Some early reports have suggested that this drug may contribute to heart failure or make existing conditions worse.
• If you have any other medical conditions such as kidney disease, heart disease, diabetes, gout, or infections. These conditions may require that your medicine dose, regimen, or timing be changed.
• If you have thyroid problems or take thyroid hormones. This medicine may affect your thyroid and require more thyroid hormone. Your doctor may want to watch your thyroid tests more closely.
• If you are taking the blood-thinning medicine warfarin (Coumadin) -- see "Interactions" below. You may need a different medicine while you are getting this drug.
• 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. 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

Imatinib can interact with a number of drugs and supplements, which may either raise or lower the level of imatinib in your blood. The following drugs can also cause imatinib 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 imatinib without talking with the prescribing doctor(s) about all of the medicines you take, including imatinib.
These drugs and supplements can lower the levels of imatinib 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), 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 imatinib.
Imatinib may change the blood levels of other drugs you are taking, including acetaminophen (Tylenol), quinidine, cyclosporine (Sandimmune), alfentanil (Alfenta), fentanyl (Duragesic, Actiq, Fentora, Onsolis), pimozide (Orap), sirolimus (Rapamune), tacrolimus (Prograf), ergotamine (Ergomar), birth control pills, some calcium channel blockers (amlodipine, nifedipine) and some cholesterol-lowering drugs (simvastatin, pravastatin, atorvastatin, etc.). The sedatives alprazolam (Xanax) and triazolam (Halcion) may also be affected. Tell your doctor if you are taking any of these drugs. You may need a different dose or a different medicine.
Imatinib can also change the blood levels of warfarin (Coumadin). If you are taking this drug to help prevent blood clots, your doctor may need to switch you to another medicine during treatment with imatinib.
Do not take iron or vitamin supplements that contain iron while taking imatinib unless your doctor tells you to.
Any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with imatinib. These include:

• vitamin E
• non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and many others
• warfarin (Coumadin -- see note above)
• 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. Grapefruit may raise the level of imatinib in your blood and cause worse side effects. 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?

Imatinib comes as a capsule or tablet taken by mouth. It is usually taken once a day. At higher doses, you may be asked to split the dose in half, taking it once in the morning and once later in the day. The dose depends on the reason you are taking it and on other factors such as your blood counts, liver and kidney function.
Imatinib can cause stomach irritation if taken on an empty stomach, so it should be taken with a meal and a large glass of water. If you have trouble swallowing, the tablet may be completely dissolved in water or apple juice, then swirled and swallowed. Do not crush imatinib tablets, and do not touch crushed tablets. If you touch crushed tablets, wash the skin thoroughly.
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. Store 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, especially warfarin (Coumadin). See interactions above. Be sure your doctor is aware of all drugs and supplements you are taking. Do not start or stop any drugs without talking to your doctor about all the drugs you are taking.
You may have nausea and vomiting on the day you receive this drug or in the first few days afterward. Your doctor may give you medicine before your treatment to help prevent nausea and vomiting. You may also get a prescription for an anti-nausea medicine that you can take at home. It is important to have these medicines on hand and to take them as prescribed by your doctor. Let your doctor know if these medicines do not control the vomiting.
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 the doctor know if the medicines don't control the diarrhea.
Imatinib may cause fluid buildup in the chest or abdomen and swelling around the eyes or in the hands or feet (edema). Some early reports have suggested this may be due the effects of this drug on the heart. Tell your doctor or nurse right away if you notice rapid weight gain, swelling around your eyes or in your hands or feet, swelling in your abdomen, or have trouble breathing (shortness of breath). You may want to check your weight each morning before you eat or drink, and report increases to your doctor.
Imatinib may affect your liver, which could increase liver enzyme levels in your blood. Your doctor will likely check your liver function with blood tests on a regular basis. The drug may need to be stopped or the dose changed if the effects are severe. If you have liver problems before starting treatment, the doctor may need to monitor you more carefully. Call your doctor if your urine becomes dark, or if your skin or eyes start to look yellow.
While taking this medicine, and a few days afterward, there is a small chance of a serious skin reaction. Symptoms often start as a skin rash with redness or blistering in the mouth, nose, or eyes, along with fever and body aches. If this happens, call your doctor right away.
Your doctor will likely test your blood throughout your treatment, looking for possible 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 altogether. 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.
This drug may lower your platelet count in the weeks after it is given, which can 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.
Rarely, imatinib can cause holes (perforations) in the digestive tract, which can be life-threatening. People who have had peptic ulcers, diverticulosis, or diverticulitis are at higher risk, as are people taking steroids, aspirin-like drugs, or certain other drugs used to treat cancer. Tell your doctor or nurse right away if you develop severe stomach (abdominal) pain, especially if you also have nausea, constipation, or any other symptom.
This drug can cause the rapid killing of tumor cells, which in some cases has led to a serious imbalance of electrolytes in the blood, and even kidney damage within the first 3 days of treatment. This condition is known as tumor lysis syndrome. It is more likely if you have a large number of cancer cells in the body. If your doctor feels you might be at risk, he or she will give you medicines and/or fluids to help prevent it.
Do not get any immunizations (vaccines), either during or after treatment with this drug, without your doctor's OK. Imatinib 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. Talk with your doctor about this.
Avoid pregnancy while taking this drug and for some time afterward. 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

• nausea*
• vomiting*
• swelling around the eyes or feet (edema)*
• weight gain due to fluid buildup*
• diarrhea*
• muscle aches and pains
• muscle cramps
• skin rash
• tiredness (fatigue)
• headache
• joint and bone pain
• abdominal (belly) pain

Less common

• low platelet count with increased risk for bleeding*
• low white blood cell count with increased risk for infection*
• severe fluid buildup in the lining of the lungs (pleural effusion), heart (pericardial effusion), or abdomen (ascites)*
• heartburn
• itching
• shortness of breath*
• constipation
• bleeding
• cough
• dizziness
• throat pain, sore throat
• infection with fever
• trouble sleeping
• depression
• low blood level of potassium
• slowed growth in children and teens
• abnormal blood tests which suggest that the drug is affecting the liver (Your doctor will discuss the importance of this finding, if any.)*

Rare

• serious skin reactions, including blistering*
• bleeding from the stomach or intestines*
• hole (perforation) in the digestive tract*
• low thyroid function
• low red blood cell count
• congestive heart failure (can cause shortness of breath or swelling in hands or feet)*
• damage to kidneys, kidney failure
• imbalance of electrolytes in the blood (tumor lysis syndrome)*
• allergic reaction -- swelling of mouth, face or throat; trouble breathing or swallowing; itching; shock
• death due to bowel perforation, lung failure, liver failure, fluid around the heart or the brain, tumor lysis syndrome, or other cause

*See "Precautions" section for more detailed information.
There are some 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 2001.
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.