***As of October 31, 2013, sales of this drug have been suspended at the request of the FDA because of concerns about high rates of serious blood clots. It’s not clear at this time if or when this suspension will be lifted. People who are taking or are planning to start this drug should talk with their doctor about this. There are still ways to get access to this drug if it is needed.***
Trade/other name(s): Iclusig
Why would this drug be used?
This drug is used to treat chronic myelogenous leukemia (CML) and some forms of acute lymphocytic leukemia (ALL). It is also being studied for use against other cancers and non-cancerous conditions.
How does this drug work?
Ponatinib is a type of targeted therapy called a tyrosine kinase inhibitor. Tyrosine kinases are proteins on or near the surface of a cell that send signals to the cell’s control center. Some of these signals may tell cancer cells to grow and divide. Ponatinib blocks these signals, which helps stop cancer cells from growing.
Before taking this medicine
Tell your doctor…
- If you are allergic to any medicines, dyes, additives, or foods.
- If you have a history of blood clots. This drug can increase your risk of blood clots in your blood vessels, which might lead to heart attack, stroke, or death (see “Precautions”).
- If you have history of heart problems, including chest pain, heart attack, heart failure, irregular heartbeats, or long QT syndrome. This drug may cause heart failure, irregular heart rhythms, or a heart attack (see “Precautions”).
- If you have high blood pressure. This drug might raise blood pressure. Your blood pressure should be checked and well controlled before starting this drug, and your doctor will monitor it closely during treatment (see “Precautions”).
- If you have bleeding problems, such as coughing up blood or having blood in your urine or stool. This drug may make bleeding worse, which in some cases may be life threatening (see “Precautions”).
- If you have a wound that is not healed or are planning to have surgery soon. This drug may affect wound healing, so it should be stopped at least 1 week before any surgery.
- If you have a history of pancreatitis (inflammation of the pancreas). This drug can raise your risk of pancreatitis (see “Precautions”).
- If you have any type of liver disease (including hepatitis). This drug may affect the liver, which in some cases can be serious. Your doctor will use blood tests to check your liver function during treatment and may need to adjust your dose accordingly (see “Precautions”).
- If you have any other medical conditions such as kidney disease, gout, diabetes, or infections. These conditions may require more careful monitoring by your doctor.
- If you are lactose intolerant. This drug contains lactose.
- 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 (see “Precautions”).
- 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 might 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
Ponatinib can interact with a number of drugs and supplements, so it is important to tell your health care team about all of your medicines and to check with them before starting or stopping any medicines.
Some drugs and supplements could cause ponatinib levels to build up in your blood. This might worsen side effects and other problems, so your dose of ponatinib might need to be reduced:
- Some antibiotics, such as erythromycin, clarithromycin (Biaxin), telithromycin (Ketek), and similar drugs
- Anti-fungal medicines such as ketoconazole (Nizoral), itraconazole (Sporanox), voriconazole (Vfend), and posaconazole (Noxafil)
- Some anti-depressant drugs, such as nefazodone (Serzone)
- Anti-HIV drugs such as indinavir (Crixivan), ritonavir (Kaletra), nelfinavir (Viracept), atazanavir (Reyataz), saquinavir (Invirase), and others
- Drugs used to treat hepatitis C virus (HCV) infection, such as boceprevir (Victrelis) and telaprevir (Incivek)
Some drugs and supplements can lower the levels of ponatinib in the blood, which might make it less effective. These drugs should be avoided unless the benefit of taking them outweighs the risk of having lower blood levels of ponatinib:
- Anti-seizure drugs, such as carbamazepine (Tegretol), phenobarbital (Solfoton), and phenytoin (Dilantin)
- Drugs to treat tuberculosis (TB), such as rifampin (Rifadin, Rimactane; also in Rifamate and Rifater), rifabutin (Mycobutin), and rifapentine (Prifin)
- The steroid drug dexamethasone (Decadron)
- St. John’s wort (herbal dietary supplement)
Many drugs used to treat heartburn, reflux, or ulcers can reduce the acid levels in the stomach, which can affect the amount of ponatinib your body can absorb. These drugs should be avoided unless the benefit of taking them outweighs the risk of having lower blood levels of ponatinib. Tell your doctor if you are taking:
- H2 blockers such as cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), or nizatidine (Axid)
- Proton pump inhibitors such as omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), rabeprazole (AcipHex), lansoprazole (Prevacid), or dexlansoprazole (Dexilant).
- Antacids such as Maalox, Mylanta, Tums, etc.
Drugs or supplements that interfere with blood clotting might raise the risk of bleeding during treatment with ponatinib. These include:
- Vitamin E
- Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and many others
- Warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), or other blood thinners, including any type of heparin injections
- Clopidogrel (Plavix)
Note that many cold, flu, fever, and headache remedies contain aspirin or ibuprofen. Ask your doctor or pharmacist before taking any of these medicines.
Other medicines or supplements may affect blood levels of ponatinib, or levels of these drugs may be affected by taking ponatinib. Make sure your doctor knows about all of the drugs and supplements you are taking.
Check with your doctor, nurse, or pharmacist about all of your medicines, herbs, and supplements, and whether alcohol can cause problems with this medicine.
Interactions with foods
Grapefruit, grapefruit juice, or grapefruit extract may affect the amount of ponatinib in your body. You should avoid grapefruit products while taking this drug. Check with your doctor, nurse, or pharmacist about whether any other specific foods could 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?
Ponatinib is a pill taken by mouth. The usual starting dose is 45 milligrams (mg), but it may be lower if you are taking certain other drugs. The dose may need to be delayed and/or adjusted if you have certain side effects during treatment.
Swallow the tablets whole, with water. Do not crush, cut, chew, or break tablets. The tablets may be taken with or without food, but avoid grapefruit or grapefruit juice.
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 away from children and pets.
Ponatinib may cause a number of side effects, some of which can be serious or even life threatening. Be sure to follow your doctor’s instructions for taking this drug and report any new side effects right away.
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.
This drug may raise your risk of problems due to blood clots, including heart attacks, strokes, transient ischemic attacks (“mini-strokes”), blood clots in leg veins or arteries, and blood clots in the lung (pulmonary embolism). Call your doctor right away if you have chest pain; shortness of breath; sudden sweating; lightheadedness; vision changes; numbness or weakness on one side of the body; trouble speaking or moving; severe headache; swelling, pain, redness, or warmth in an arm or leg; or severe pain or coldness in an arm, hand, foot, or leg.
This drug may cause liver damage, which in some cases may be serious or even life threatening. Your doctor will test your blood for signs of liver damage before and during treatment and may need to reduce or delay your next dose of this drug, or even stop it altogether. Tell your doctor or nurse if you have symptoms that might be related to liver damage, such as yellowing of the skin or the whites of your eyes (jaundice), dark urine, nausea or vomiting, pain on the right side of your belly, or any abnormal bruising or bleeding.
This drug may cause damage to the heart. Your doctor will watch you closely for signs of heart damage while you are getting this drug. Possible symptoms of heart damage might include chest pain, increased coughing, trouble breathing (especially at night), rapid weight gain (5 pounds or more in 24 hours), dizziness, fainting, or swelling in the ankles or legs. Tell your doctor right away if you start to notice any of these symptoms once treatment starts.
Ponatinib may cause high blood pressure or make it worse. 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. If your blood pressure goes up, you may need to take medicine to help control it. Your doctor may need to adjust your dose or delay treatment with this drug if you have high blood pressure that can’t be controlled. If the high blood pressure is severe enough, you may need to stop taking this drug altogether. Tell your doctor right away if you notice any possible symptoms of high blood pressure, including a severe headache, confusion, feeling dizzy or light-headed, chest pain, or shortness of breath.
This drug can cause pancreatitis (inflammation of the pancreas) in some people. Your doctor will test your blood for signs of pancreatitis during treatment and may need to reduce or delay your next dose of this drug, or even stop it altogether. Tell your doctor or nurse if you have symptoms that might be related to pancreatitis, such as nausea, vomiting, or sudden severe abdominal (belly) pain.
This drug may increase your risk of bleeding, which in some cases can be serious or even life threatening. 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, blood thinners like warfarin (Coumadin), or vitamin E (see “Interactions”). Tell your doctor right away if you cough up or vomit blood or have unusual bruising or bleeding, such as nosebleeds, heavy menstrual bleeding, bleeding gums when you brush your teeth, or black, tarry stools.
Ponatinib may cause fluid to build up around your brain or heart, in or around your lungs, or in your abdomen. It may also cause swelling around your eyes or in your hands or feet (edema). Tell your doctor or nurse right away if you gain weight, have swelling around your eyes or in your hands or feet, notice bloating or swelling in your abdomen, or have chest pain, a new cough, or trouble breathing.
This drug may affect the heart’s rhythm, which in some cases can lead to serious problems. Tell your doctor if you have ever been diagnosed with any type of heart disease, especially an abnormal heart rhythm or long QT syndrome. Tell your doctor right away if you notice a fast or irregular heartbeat, chest pain, lightheadedness, dizziness, or shortness of breath.
In rare cases, this drug can cause the rapid killing of tumor cells, which can lead to serious kidney damage within the first 24 hours of treatment (a condition known as tumor lysis syndrome). This is more likely if you have advanced leukemia and a very 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 this.
Rarely, ponatinib can cause holes (perforations) in the digestive tract, which can be life-threatening. Tell your doctor or nurse right away if you have severe stomach (abdominal) pain, have a high fever, are vomiting blood, or if you have red or very dark colored stools.
This drug can affect your body’s ability to heal wounds. It should not be used within 1 week before any planned surgery (including dental procedures) and should not be started again until the surgical wound is adequately healed.
Your doctor will test your blood before and during your treatment to check for the effects of the drug on blood cell counts. Based on the test results, your doctor may need to reduce or delay your next dose of this drug, or even stop it altogether. Keep all your appointments for doctor visits and lab tests.
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, a new cough, or bringing up sputum.
Do not get any immunizations (vaccines), either during or after treatment with this drug, without your doctor’s OK. This drug may affect your immune system, which could make vaccinations ineffective, or could even lead to serious infections. 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.
This drug should not be taken if you are pregnant or breast-feeding. Ponatinib can cause problems with the fetus if taken at the time of conception or during pregnancy. Women who are taking this drug should use effective birth control during treatment. Check with your doctor about what kinds of birth control can be used with this medicine. This drug may also pass into breast milk, which could affect the baby.
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.
- High blood pressure*
- Rash or dry skin
- Abdominal (belly) pain
- Feeling weak or tired
- Muscle or joint pain
- Abnormal blood tests suggesting drug may be affecting the liver, pancreas, or blood mineral levels (Your doctor will discuss the importance of these findings, if any.)*
- Low blood platelet count, which can increase the risk of bleeding
- Low counts of certain white blood cells (neutropenia), which can increase the risk of serious infection*
- Heart attack, stroke, or blood clots in the legs or lungs*
- Back pain
- Numbness, tingling, or pain in the hands, feet, or elsewhere
- Shortness of breath
- Swelling in the hands or feet*
- Bone pain
- Respiratory infection (such as a cold, bronchitis, or pneumonia)
- Feeling dizzy
- Mouth sores
- Urinary tract infection
- Loss of appetite
- Weight loss
- Trouble sleeping
- Heart failure*
- Low red blood cell count (anemia)
- Bleeding in the digestive tract or elsewhere*
- Changes in heart rhythm*
- Fluid build-up around the brain or heart, or in or around the lungs*
- Pancreatitis (inflammation of the pancreas)*
- Kidney damage from tumor lysis syndrome*
- Holes (perforations) in the digestive tract*
- Bacteria in the blood or blood infections
- Death due to heart failure, bleeding, infection, or other causes
*See “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.
Yes – first approved in 2012
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.
Last Revised: 01/03/2013