Ponatinib

Ponatinib is a prescription medication used to treat a certain type of chronic myeloid leukemia (CML). Ponatinib is also used to treat a certain type of acute lymphoblastic leukemia (ALL). Ponatinib belongs to a group of drugs called kinase inhibitors. These work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.

Ponatinib comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take ponatinib at around the same time every day.

Common side effects include high blood pressure, rash, stomach pain, and fatigue. Do not drive or operate heavy machinery until you know how this medication affects you.

Ponatinib is a prescription medication used to treat a certain type of chronic myeloid leukemia (CML). CML is a type of cancer of the white blood cells. Ponatinib is also used to treat a certain type of acute lymphoblastic leukemia (ALL) in people who can no longer benefit from other medications for leukemia or who cannot take these medications because of side effects. ALL is a type of cancer of the white blood cells.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Common side effects include the following:

• elevated blood pressure
• rash
• stomach pain
• fatigue
• headache
• dry skin
• constipation
• joint pain
• nausea
• fever
• low blood counts

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• antacids, such as aluminum hydroxide/magnesium hydroxide (Maalox), calcium carbonate (Tums) or calcium carbonate and magnesium (Rolaids)
• boceprevir (Victrelis)
• certain antifungals such as itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), and voriconazole (Vfend)
• certain medications for seizures such as carbamazepine (Carbatrol, Tegretol) and phenytoin (Dilantin, Phenytek)
• clarithromycin (Biaxin, in PrevPac)
• certain medications used to treat human immunodeficiency virus (HIV) such as indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase)
• conivaptan (Vaprisol)
• medications to reduce stomach acid, such as cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac); nefazodone
• proton pump inhibitors (PPIs) such as esomeprazole (Nexium), omeprazole (Prilosec, Prilosec OTC, Zegerid), pantoprazole (Protonix)
• rifampin (Rifadin, Rifamate, Rifiter)
• telaprevir (Incivek)
• telithromycin (Ketek)

This is not a complete list of all drug interactions. Ask your doctor or pharmacist for more information.

Ponatinib can cause serious side effects, including the following:

• Blood clots or blockage in your blood vessels (arteries and veins). Blood clots or blockage in your blood vessels may lead to heart attack, stroke, or death. A blood clot or blockage in your blood vessels can prevent proper blood flow to your heart, brain, bowels (intestines), legs, eyes, and other parts of your body. You may need emergency surgery or treatment in a hospital. Get medical help right away if you get any of the following symptoms:
  • chest pain or pressure
  • pain in your arms, legs, back, neck or jaw
  • shortness of breath
  • numbness or weakness on one side of your body
  • trouble talking
  • headache
  • dizziness
  • severe stomach area pain
  • decreased vision or loss of vision
• Blood clots or blockage in your blood vessels can happen in people with or without risk factors for heart and blood vessel disease, including people 50 years of age or younger. Talk to your healthcare provider if this is a concern for you.
• Heart problems. Ponatinib can cause heart problems, including heart failure which can be serious and may lead to death. Heart failure means your heart does not pump blood well enough. Ponatinib can also cause irregular slow or fast heartbeats and heart attack. Your healthcare provider will check your heart function before and during your treatment with ponatinib. Get medical help right away if you get any of the following symptoms: shortness of breath, chest pain, fast or irregular heartbeats, dizziness, or feel faint.
• Liver problems. Ponatinib can cause liver problems, including liver failure, which can be severe and may lead to death. Your healthcare provider will do blood tests before and during your treatment with ponatinib to check for liver problems. Get medical help right away if you get any of these symptoms of liver problems during treatment:
  • yellowing of your skin or the white part of your eyes (jaundice)
  • dark "tea-colored" urine
  • sleepiness

• High blood pressure. Your blood pressure should be checked regularly and any high blood pressure should be treated while you are taking ponatinib. Tell your healthcare provider if you get headaches, dizziness, chest pain or shortness of breath.
• Inflammation of the pancreas (pancreatitis). Symptoms include sudden stomach-area pain, nausea, and vomiting. Your healthcare provider should do blood tests to check for pancreatitis during treatment with ponatinib.
• Neuropathy. Ponatinib may cause damage to the nerves in your arms, brain, hands, legs, or feet (Neuropathy). Tell your healthcare provider if you get any of these symptoms during treatment with ponatinib:
  • muscle weakness, tingling, burning, pain, and loss of feeling in your hands and feet
  • double vision and other problems with eye sight, trouble moving the eye, drooping of part of the face, sagging or drooping eyelids
• Effects on the eye. Serious eye problems that can lead to blindness or blurred vision may happen with ponatinib. Tell your healthcare provider if you get any of the following symptoms: perceived flashes of light, light sensitivity, floaters, dry or itchy eyes, and eye pain. Your healthcare provider will monitor your vision before and during your treatment with ponatinib.
• Severe bleeding. Ponatinib can cause bleeding which can be serious and may lead to death. Tell your healthcare provider if you get any signs of bleeding while taking ponatinib including:
  • vomiting blood or if your vomit looks like coffee-grounds
  • pink or brown urine
  • red or black (looks like tar) stools
  • coughing up blood or blood clots
  • unusual bleeding or bruising of your skin
  • menstrual bleeding that is heavier than normal
  • unusual vaginal bleeding
  • nose bleeds that happen often
  • drowsiness or difficulty being awakened
  • confusion
  • headache
  • change in speech
• Fluid retention. Your body may hold too much fluid (fluid retention). Tell your healthcare provider right away if you get any of these symptoms during treatment with ponatinib:
  • swelling of your hands, ankles, feet, face, or all over your body
  • weight gain
  • shortness of breath and cough
• Low blood cell counts. Ponatinib may cause low blood cell counts. Your healthcare provider will check your blood counts regularly during treatment with ponatinib. Tell your healthcare provider right away if you have a fever or any signs of an infection while taking ponatinib.
• Tumor Lysis Syndrome (TLS). TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have:
  • kidney failure and the need for dialysis treatment
  • an abnormal heartbeat
  Your healthcare provider may do blood tests to check for TLS.
• Possible wound healing problems. If you need to have a surgical procedure, tell your healthcare provider that you are taking ponatinib. You should stop taking ponatinib at least 1 week before any planned surgery.
• A tear in your stomach or intestinal wall (perforation). Tell your healthcare provider right away if you get:
  • severe pain in your stomach-area (abdomen)
  • swelling of the abdomen
  • high fever

Grapefruit and grapefruit juice may interact with this medication and can lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before you take ponatinib, tell your healthcare provider if you:

• have a history of blood clots in your blood vessels (arteries or veins)
• have heart problems, including heart failure, irregular heartbeats, and QT prolongation
• have diabetes
• have a history of high cholesterol
• have liver problems
• have had inflammation of your pancreas (pancreatitis)
• have high blood pressure
• have bleeding problems
• plan to have any surgical procedures
• are lactose (milk sugar) intolerant. ponatinib tablets contain lactose.
• drink grapefruit juice
• have any other medical conditions
• are pregnant or plan to become pregnant. Ponatinib can harm your unborn baby. You should not become pregnant while taking ponatinib. Tell your healthcare provider right away if you become pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. It is not known if ponatinib passes into your breast milk. You and your healthcare provider should decide if you will take ponatinib or breastfeed. You should not do both.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. Ponatinib can harm your unborn baby. You should not become pregnant while taking ponatinib. Tell your healthcare provider right away if you become pregnant or plan to become pregnant.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if this medication crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using this medication.

• Take ponatinib exactly as your healthcare provider tells you to take it.
• Your healthcare provider may change your dose of ponatinib or tell you to stop taking Iclusig.
• Do not change your dose or stop taking ponatinib without talking to your healthcare provider.
• Swallow ponatinib tablets whole. Do not crush or dissolve ponatinib tablets.
• You may take ponatinib with or without food.
• If you miss a dose of ponatinib, take your next dose at your regular time. Do not take 2 doses at the same time to make up for a missed dose.
• If you take too much ponatinib, call your healthcare provider or go to the nearest hospital emergency room right away.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.
The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

The recommended dose is 45 mg taken orally once daily with or without food.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Store at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep this and all other medications out of the reach of children.

• Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion.
• Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.
• Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.