Ponatinib (Iclusig®)

How to Take Ponatinib

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. Swallow the tablets whole. Do not crush, chew, or break the tablets. If you miss a dose, take the next dose at the regular time. Do not take 2 doses to make up for the missed dose.

It is important to make sure you are taking the correct amount of medication every time. Before every dose, check that what you are taking matches what you have been prescribed.

The blood levels of this medication can be affected by certain foods and medications, so they should be avoided. These include: grapefruit, grapefruit juice, verapamil, ketoconazole, rifampin, phenytoin, St. John’s wort, and modafinil. Be sure to tell your healthcare provider about all medications and supplements you take.

Storage and Handling

Store your medication in the original, labeled container at room temperature and in a dry location (unless otherwise directed by your healthcare provider or pharmacist). This medication should not be stored in a pillbox. Keep containers out of reach of children and pets.

If a caregiver prepares your dose for you, they should consider wearing gloves or pour the pills directly from their container into the cap, a small cup, or directly into your hand. They should avoid touching the pills. They should always wash their hands before and after giving you the medication. Pregnant or nursing women should not prepare the dose for you. Ask your oncology team where to return any unused medication for disposal. Do not flush down the toilet or throw in the trash.

Where do I get this medication?

Certain cancer medications, including ponatinib, are only available through specialty pharmacies. If you need to get this medication through a specialty pharmacy, your provider will help you start this process. Where you can fill your prescriptions may also be influenced by your prescription drug coverage. Ask your health care provider or pharmacist for assistance in identifying where you can get this medication.

Insurance Information

This medication may be covered under your prescription drug plan. Patient assistance may be available to qualifying individuals depending upon prescription drug coverage. Co-pay cards, which reduce the patient co-pay responsibility for eligible commercially (non-government sponsored) insured patients, may also be available. Your care team can help you find these resources, if they are available.

Possible Side Effects of Ponatinib

There are a number of things you can do to manage the side effects of ponatinib. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Blood Clots, Stroke and Heart Attack

Ponatinib can increase the risk of blood clots, stroke, and heart attack. It can also cause blockages or clots in your blood vessels. If you have any of thr symtpoms listed below, contact your healthcare provider right away or go to an emergency room.

Symptoms can include: swelling, redness, or pain in an extremity (arm or leg), chest pain or pressure, pain in your arm, back, neck or jaw, shortness of breath, numbness or weakness on one side of the body, trouble talking, confusion or mental status changes. Let your care team know if you have a history of previous blood clots, as you may need preventive medication.

Heart Problems

This medication can cause or worsen pre-existing heart problems including congestive heart failure, restrictive cardiomyopathy, decreased heart function, and heart attack. Tell your healthcare provider if you have sudden weight gain or swelling in the ankles or legs. If you have chest pain or pressure, pain in the left arm, back, or jaw, sweating, shortness of breath, clammy skin, nausea, dizziness or lightheadedness, call 911 or go to the nearest emergency room.

Liver Toxicity

This medication can cause liver toxicity, which your provider may monitor for using blood tests called liver function tests. If your liver function tests are high, your healthcare provider may need to lower your dose or stop the medication. Tell your care team if you notice yellowing of your skin or eyes, if your urine looks dark or brown, or if you have pain in your abdomen (belly), as these can be signs of liver toxicity.

High Blood Pressure

This medication can cause high blood pressure (hypertension). You should have your blood pressure checked regularly during therapy. Hypertension should be treated appropriately. If hypertension cannot be controlled, ponatinib may be stopped. Report any headaches, vision changes, or dizziness to your oncology care team.

Low White Blood Cell Count (Leukopenia or Neutropenia)

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your care team know right away if you have a fever (temperature greater than 100.4°F or 38°C), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips to preventing infection:

• Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
• Avoid large crowds and people who are sick (i.e.: those who have a cold, fever, or cough or live with someone with these symptoms).
• When working in your yard, wear protective clothing including long pants and gloves.
• Do not handle pet waste.
• Keep all cuts or scratches clean.
• Shower or bathe daily and perform frequent mouth care.
• Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
• Ask your oncology care team before scheduling dental appointments or procedures.
• Ask your oncology care team before you, or someone you live with has any vaccinations.

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your oncology care team know if you experience any shortness of breath, difficulty breathing, or pain in your chest. If the count gets too low, you may receive a blood transfusion.

Low Platelet Count (Thrombocytopenia)

Platelets help your blood clot, so when the count is low, you are at a higher risk of bleeding. Let your oncology care team know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums, or blood in your urine or stool. If your platelet count becomes too low, you may need a transfusion of platelets.

• Do not use a razor (an electric razor is fine).
• Avoid contact sports and activities that can result in injury or bleeding.
• Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib) etc. as these can all increase the risk of bleeding. Please consult with your healthcare team regarding the use of these agents and all over-the-counter medications/supplements while on therapy.
• Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.

Rash and Dry Skin

Some patients may develop a rash, scaly skin, or red itchy bumps. Use an alcohol-free moisturizer on your skin and lips; avoid moisturizers with perfumes or scents. Your oncology care team can recommend a topical medication if you have itching. If your skin cracks or bleeds, be sure to keep the area clean to avoid infection. Tell your oncology care team about any rash you have, as this can be a reaction. They can give you more tips on caring for your skin.

Fatigue

Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue. A simple daily walk with a friend can help. Talk to your care team for helpful tips on dealing with fatigue.

Constipation

There are several things you can do to prevent or relieve constipation. Include fiber in your diet (fruits and vegetables), drink 8-10 glasses of non-alcoholic fluids a day, and keep active. A stool softener once or twice a day may prevent constipation. If you do not have a bowel movement for 2-3 days, you should contact your healthcare team for suggestions to relieve the constipation.

Nausea and Vomiting

Talk to your provider so they can prescribe medications to help manage nausea and vomiting. In addition, dietary changes may help. Avoid things that may make the symptoms worse, such as heavy or greasy/fatty, spicy, or acidic foods (lemons, tomatoes, oranges). Try antacids, (e.g. milk of magnesia, calcium tablets such as Tums), saltines, or ginger ale to lessen symptoms.

Call your care team if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Peripheral Neuropathy (Numbness or Tingling in the Hands and/or Feet)

Peripheral neuropathy is a toxicity that affects the nerves. It causes numbness or tingling in the hands and feet, often in the pattern of a stocking or glove. This can get worse with more doses of the medication. In some people, the symptoms slowly get better after the medication is stopped, but for some it never goes away completely. You should let your healthcare provider know if you have numbness or tingling in your hands and feet, as they may need to change the doses of your medication.

High Blood Sugar

This medication can cause high blood sugar levels in patients with and without diabetes. Your oncology care team will monitor your blood sugar. If you have increased thirst, urination or hunger, blurry vision, headaches, or if your breath smells like fruit, call your care team. Diabetics should monitor their blood sugar closely and report high levels to their provider.

Muscle or Joint Pain/Aches and Headache

This medication can cause muscle and joint pain and aches, as well as headaches. Your healthcare provider can recommend medications and other strategies to help relieve pain.

Less common, but important side effects can include:

• Other Heart Problems: This medication can cause slow or abnormal heartbeats or an abnormal heart rhythm called QT prolongation. Call your oncology care team right away if you feel abnormal heartbeats or if you feel dizzy or faint.
• Fluid Retention: Ponatinib can cause fluid retention (your body holds on to too much fluid). This may lead to fluid in your lungs (pleural effusion) or heart (pericardial effusion), and swelling of your arms or legs. Tell your care team if you have swelling in your arms, legs, feet, or abdomen (belly), have an unexpected weight gain, racing heartbeat, shortness of breath, or difficulty breathing, or if you develop a dry cough.
• Effects on the Pancreas: This medication can affect your pancreas. Your oncology provider will monitor for this problem with blood tests. Let your provider know if you have a history of pancreatitis or excessive alcohol use, or if you have abdominal pain or nausea and vomiting.
• Wound healing: This medication can cause slower or incomplete wound healing, such as a surgical wound not healing or staying closed. It is recommended that this medication be stopped 1 week before any surgery. Your provider will monitor wound healing before restarting this medication. If you have a surgical wound that has not healed or begins to have signs of infection (redness, swelling, warmth), report this to your healthcare team. 
• GI Tear: This medication can cause a tear in the intestinal wall, also called a gastrointestinal (GI) perforation. Signs of this can include new or worsening pain in the abdomen, new abdominal swelling, chills, fever, constipation, nausea, or vomiting. If you have any of these, call your provider right away or go to the emergency room.
• Tumor Lysis Syndrome: If there are a large amount of tumor cells in your body before you start treatment, you are at risk for tumor lysis syndrome. This happens when the tumor cells die too quickly. Their waste overwhelms the body. You may be given a medication (allopurinol) and IV fluids to help prevent this. If you have nausea, vomiting, diarrhea or become lethargic (drowsy, sluggish), call your oncology team right away. TLS can affect your kidney function. Your provider will monitor your kidney function with blood work. Tell your provider if you have little or no urine output.
• Effects on the Eyes: This medication can cause eye problems. Your provider may have your eyes examined before and/or during treatment. Be sure to report any symptoms of eye problems to your oncology provider, including blurred vision, changes in vision, dry eye, eye pain, yellowing of colors or seeing "floaters" or spots in your field of vision.
• Posterior Reversible Encephalopathy Syndrome (PRES): In rare cases, this medication has caused a neurological disorder called posterior reversible encephalopathy syndrome (PRES), also called reversible posterior leukoencephalopathy (RPLS). Symptoms of PRES/RPLS include headache, seizure, lethargy, confusion, blindness, and other visual and neurological disturbances. Report any of these symptoms to your healthcare team immediately.

Reproductive Concerns

This medication may affect the reproductive system of women, resulting in the menstrual cycle becoming irregular or stopping permanently. Women may experience menopausal effects including hot flashes and vaginal dryness. In addition, the desire for sex may decrease during treatment. You may want to consider egg harvesting if you may wish to have a child in the future. Discuss these options with your oncology team.

Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. Effective birth control is necessary during treatment and for 3 weeks after treatment ends. Even if your menstrual cycle stops or you believe you are not producing sperm, you could still be fertile and conceive. You should not breastfeed while taking this medication or for 6 days after your last dose.