Ponatinib, Oral

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KEY POINTS

• This medicine is taken by mouth to treat certain kinds of leukemia. Take it exactly as directed.
• This medicine may increase the chance of heart attack, stroke, blood clots, and death. This medicine may also cause severe or life-threatening liver problems.
• You may get infections more easily when you are taking this medicine.
• Keep all appointments for tests to see how this medicine affects you.
• This medicine may cause unwanted side effects. Tell your healthcare provider if you have any side effects that are serious, continue, or get worse.
• Tell all healthcare providers who treat you about all the prescription medicines, nonprescription medicines, supplements, natural remedies, and vitamins that you take.

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What are other names for this medicine?

Type of medicine: tyrosine kinase inhibitor; antineoplastic (anticancer)

Generic and brand names: ponatinib, oral; Iclusig

What is this medicine used for?

This medicine is taken by mouth to treat

• Chronic myeloid leukemia (CML), a cancer of the bone marrow
• Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL)

This medicine is used when other treatments have not been effective.

This medicine may be used to treat other conditions as determined by your healthcare provider.

What should my healthcare provider know before I take this medicine?

Before taking this medicine, tell your healthcare provider if you have ever had:

• An allergic reaction to any medicine or to lactose
• A stroke or transient ischemic attack (TIA)
• Bleeding problems or blood clots
• Diabetes
• Edema (fluid buildup)
• Heart problems such as heart failure, an irregular heartbeat, or a heart attack
• High blood pressure
• High cholesterol
• Liver disease
• Long QT syndrome (problems with electrical activity in the heart muscle)
• Pancreatitis
• Problems with alcohol abuse

Also tell your provider if you are planning to have surgery or have recently had surgery.

Females of childbearing age: This medicine is not usually given to pregnant women because it can harm the baby. If you are pregnant, tell your healthcare provider. Do not become pregnant during treatment with this medicine. If you become pregnant, contact your healthcare provider right away. Do not breast-feed while you are receiving this medicine.

How do I take it?

Read the Medication Guide that comes in the medicine package when you start taking this medicine and each time you get a refill.

Check the label on the medicine for directions about your specific dose. Take this medicine exactly as your healthcare provider prescribes. Do not stop taking this medicine without your healthcare provider's approval. Treatment will be continued for as long as you continue to benefit and can tolerate the side effects.

Check with your healthcare provider before using this medicine in children under age 18.

You may take this medicine with or without food. Taking it with meals and with a large glass of water may lessen the chance the drug will upset your stomach.

Do not crush or chew the tablets. Swallow them whole.

Depending on your condition, your healthcare provider may adjust your daily dosage. Follow your healthcare provider's directions exactly.

What if I miss a dose?

If you miss a dose, take it as soon as you remember unless it is almost time for the next scheduled dose. In that case, skip the missed dose and take the next one as directed. Do not take double doses. If you are not sure of what to do if you miss a dose, or if you miss more than one dose, contact your healthcare provider.

What if I overdose?

If you or anyone else has intentionally taken too much of this medicine, call 911 or go to the emergency room right away. If you pass out, have seizures, weakness or confusion, or have trouble breathing, call 911. If you think that you or anyone else may have taken too much of this medicine, call the poison control center. Do this even if there are no signs of discomfort or poisoning. The poison control center number is 800-222-1222.

Symptoms of an acute overdose may include: chest pain, irregular heartbeat, tiredness.

What should I watch out for?

This medicine may cause blood clots or blockage in your blood vessels and increase the chance of heart attack, stroke, and death. This can happen even if you are under age 50 and have never had heart or blood vessel problems. Talk with your provider about this.

This medicine may cause serious or life-threatening heart problems, including heart failure, heart attack, or irregular heartbeats. Your healthcare provider may check your heart function before and during your treatment with this medicine. Contact your healthcare provider right away or get medical help right away if you experience shortness of breath, chest pain, slow, fast or irregular heartbeat, dizziness, or feel faint.

This medicine may also cause severe or life-threatening liver problems. Tell your healthcare provider right away if you have yellowing of your skin or eyes, severe nausea or vomiting, stomach pain, dark urine, unexplained loss of appetite, or light-colored bowel movements. These may be signs of liver problems.

You need to have checkups and lab tests regularly to see how this medicine affects you. Keep all appointments.

This medicine may cause fever, infection, high blood pressure, or anemia. You may get infections more easily when you are taking this medicine. Stay away from people with colds, flu, or other infections. Also, do not have any vaccines without getting your healthcare provider's approval first.

This medicine may cause the fast breakdown of certain types of cancer cells. Call your healthcare provider right away if you have a fast heartbeat or heartbeat that does not feel normal, trouble passing urine, muscle weakness or cramps, severe vomiting or diarrhea, or feel sluggish.

This medicine may cause eye problems. Have regular eye exams while you are taking this medicine.

Adults over the age of 65 may be at greater risk for side effects. Talk with your healthcare provider about this.

If you need emergency care, surgery, lab tests, or dental work, tell the healthcare provider or dentist you are taking this medicine.

What are the possible side effects?

Along with its needed effects, your medicine may cause some unwanted side effects. Some side effects may be very serious. Some side effects may go away as your body adjusts to the medicine. Tell your healthcare provider if you have any side effects that continue or get worse.

Life-threatening (Report these to your healthcare provider right away. If you cannot reach your healthcare provider right away, get emergency medical care or call 911 for help.): Allergic reaction (hives; itching; rash; trouble breathing; chest pain or tightness in your chest; swelling of your lips, tongue, and throat); sudden weakness, numbness, or tingling, especially on one side of your body; sudden or severe headache; sudden trouble with vision, speech, balance, or walking.

Serious (Report these to your healthcare provider right away.): Chest pain; fast, slow, or irregular heartbeat; pain in your arms, back, neck, or jaw; shortness of breath; severe dizziness or fainting; severe stomach pain, nausea, or vomiting; yellowing of the skin or eyes; dark urine; light-colored bowel movements; pain, warmth, or swelling in leg or arms, or any unexplained swelling; unexplained weight gain; unusual bruising or bleeding; black or tarry bowel movements; heavier menstrual bleeding; fever; sore throat; cough; severe drowsiness; severe confusion; unusual tiredness or weakness; increased, decreased, or trouble urinating; increased thirst; numbness, burning, tingling, or weakness in hands or feet; any eye pain, or dry eyes; severe mouth sores; drooping of part of the face or eyelids.

Other: Diarrhea, constipation, mild nausea, mild rash, joint or muscle pain, mild headache, dry skin, trouble sleeping.

What products might interact with this medicine?

When you take this medicine with other medicines, it can change the way this or any of the other medicines work. Nonprescription medicines, vitamins, natural remedies, and certain foods may also interact. Using these products together might cause harmful side effects. Talk to your healthcare provider if you are taking:

• Aliskiren (Tekturna) and aliskiren/hydrochlorothiazide (Tekturna HCT)
• Ambrisentan (Letairis)
• Antacids that contain aluminum, calcium, or magnesium, such as Gaviscon, Maalox, Mylanta, Phillips' Chewable Tablets, Rolaids, or TUMS
• Antibiotics such as clarithromycin (Biaxin), erythromycin (E.E.S., Ery-Tab, Erythrocin), rifabutin (Mycobutin), rifampin (Rifadin), rifapentine (Priftin), and telithromycin (Ketek)
• Antifungal medicines such as itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), and voriconazole (Vfend)
• Antiseizure medicines such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), oxcarbazepine (Trileptal), phenobarbital, phenytoin (Dilantin, Phenytek), and primidone (Mysoline)
• Aspirin and other salicylates
• Barbiturates such as butabarbital (Butisol), pentobarbital (Nembutal), phenobarbital, and secobarbital (Seconal)
• Bosentan (Tracleer)
• Clozapine (Clozaril, FazaClo)
• Colchicine (Colcrys)
• Conivaptan (Vaprisol)
• Dexamethasone
• Diabetes medicines such as saxagliptin (Onglyza), saxagliptin/metformin (Kombiglyze), simvastatin/sitagliptin (Juvisync), sitagliptin (Januvia), and sitagliptin/metformin (Janumet)
• Everolimus (Afinitor, Zortress)
• Fexofenadine (Allegra)
• Heart medicines such as amiodarone (Cordarone, Pacerone), digoxin (Lanoxin), and ranolazine (Ranexa)
• HIV medicines such as atazanavir (Reyataz), cobicistat (Tybost), darunavir (Prezista), delavirdine (Rescriptor), efavirenz (Sustiva), elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir/ritonavir (Kaletra), maraviroc (Selzentry), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir), and saquinavir (Invirase)
• Immunosuppressants such as cyclosporine (Gengraf, Neoral, Sandimmune), and sirolimus (Rapamune)
• Medicines to block or prevent stomach acid such as cimetidine (Tagamet), esomeprazole (Nexium), famotidine (Pepcid), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec), pantoprazole (Protonix), and ranitidine (Zantac)
• Medicines to treat or prevent blood clots such as abciximab (ReoPro), argatroban, bivalirudin (Angiomax), clopidogrel (Plavix), dabigatran (Pradaxa), dipyridamole (Persantine), lepirudin (Refludan), tirofiban (Aggrastat), and warfarin (Coumadin)
• Methotrexate (Otrexup, Rasuvo, Rheumatrex, Trexall)
• Nefazodone
• Other cancer medicines such as enzalutamide (Xtandi), imatinib (Gleevec), irinotecan (Camptosar), lapatinib (Tykerb), mitotane (Lysodren), mitoxantrone (Novantrone), nilotinib (Tasigna), and topotecan (Hycamtin)
• Rosuvastatin (Crestor)
• St. John's wort
• Sulfasalazine (Azulfidine)
• Tolvaptan (Samsca)

Ask your healthcare provider or pharmacist if you need to avoid products that contain grapefruit, Seville oranges, and tangelos while you are taking this medicine. These fruits and juices can affect the way this medicine works and may increase your risk of serious side effects.

Do not drink alcohol while taking this medicine unless your healthcare provider approves.

If you are not sure if your medicines might interact, ask your pharmacist or healthcare provider. Keep a list of all your medicines with you. List all the prescription medicines, nonprescription medicines, supplements, natural remedies, and vitamins that you take. Be sure that you tell all healthcare providers who treat you about all the products you are taking.

How should I store this medicine?

Store this medicine at room temperature. Keep the container tightly closed. Protect it from heat, high humidity, and bright light.

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This advisory includes selected information only and may not include all side effects of this medicine or interactions with other medicines. Ask your healthcare provider or pharmacist for more information or if you have any questions.

Ask your pharmacist for the best way to dispose of outdated medicine or medicine you have not used. Do not throw medicine in the trash.

Keep all medicines out of the reach of children.

Do not share medicines with other people.