[Posted 10/11/2013]ISSUE: FDA is investigating an increasing frequency of reports of serious and life-threatening blood clots and severe narrowing of blood vessels (arteries and veins) of patients taking the leukemia chemotherapy drug Iclusig (ponatinib). Data from clinical trials and postmarket adverse event reports show that serious adverse events have occurred in patients treated with Iclusig, including heart attacks resulting in death, worsening coronary artery disease, stroke, narrowing of large arteries of the brain, severe narrowing of blood vessels in the extremities, and the need for urgent surgical procedures to restore blood flow. FDA is actively working to further evaluate these adverse events and will notify the public when more information is available.
BACKGROUND: Iclusig is a prescription medicine used to treat adults diagnosed with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), who are no longer benefiting from previous treatment or who did not tolerate other treatment. At the time of Iclusig's approval in December 2012, the drug label contained information about the risks of blood clots in the Boxed Warning and Warnings and Precautions sections. In clinical trials conducted before approval, serious arterial blood clots occurred in 8 percent of Iclusig-treated patients, and blood clots in the veins occurred in 3 percent of Iclusig-treated patients. In the most recent clinical trial data submitted by the manufacturer to FDA, at least 20 percent of all participants treated with Iclusig have developed blood clots or narrowing of blood vessels.
RECOMMENDATION: Health care professionals should consider for each patient, whether the benefits of Iclusig treatment are likely to exceed the risks of treatment. Patients taking Iclusig should seek immediate medical attention if they experience symptoms suggesting a heart attack such as chest pain or pressure, pain in their arms, back, neck or jaw, or shortness of breath; or symptoms of a stroke such as numbness or weakness on one side of the body, trouble talking, severe headache, or dizziness. FDA is providing this information to patients and health care professionals while it continues its investigation.
For more information visit the FDA website at: Web Siteand Web Site.
Ponatinib may cause serious or life-threatening blood clots in your legs or lungs, heart attacks, or strokes. Tell your doctor if you have or have ever had a blood clot in your lungs or legs; a stroke; high blood pressure; a slow, fast, or irregular heartbeat; a heart attack; or heart failure. If you experience any of the following symptoms, call your doctor immediately: chest pain; shortness of breath; coughing up blood; rapid, irregular, or pounding heartbeat; dizziness or fainting; sudden confusion or trouble speaking or understanding; sudden numbness or weakness of face, arm, or leg on one side of the body; sudden severe headache; leg pain; feeling of warmth in the lower leg; or swelling of the feet, ankles, or lower legs.
Ponatinib may cause serious or life-threatening damage to the liver. Tell your doctor if you have or have ever had liver disease or problems with your liver. If you experience any of the following symptoms, call your doctor immediately: itching, yellow eyes or skin, dark urine, or pain or discomfort in the right upper stomach area.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to ponatinib.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with ponatinib and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide.
WHY is this medicine prescribed?
Ponatinib is used to treat a certain type of chronic myeloid leukemia (CML; a type of cancer of the white blood cells), including treatment in people who can no longer benefit from other medications for CML or who cannot take these medications because of side effects. Ponatinib is also used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer of the white blood cells) in people who can no longer benefit from other medications for leukemia or who cannot take these medications because of side effects. Ponatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.
HOW should this medicine be used?
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. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ponatinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the tablets whole; do not split, chew, or crush them.
Your doctor may adjust your dose of ponatinib depending on your response to treatment and any side effects that you experience. Talk to your doctor about how you are feeling during your treatment. Continue to take ponatinib even if you feel well. Do not stop taking ponatinib without talking to your doctor.
Are there OTHER USES for this medicine?
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What SPECIAL PRECAUTIONS should I follow?
Before taking ponatinib,
- tell your doctor and pharmacist if you are allergic to ponatinib, any other medications, or any of the ingredients in ponatinib tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: 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), 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); and telithromycin (Ketek). Many other medications may also interact with ponatinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you have or have ever had a bleeding problem; heart disease; a heart attack; a stroke; high blood pressure; diabetes; high cholesterol; pancreatitis (swelling of the pancreas, a gland behind the stomach that produces substances to help with digestion); or if you are lactose intolerant (inability to digest dairy products). Also, tell your doctor if you drink or have ever drunk large amounts of alcohol or if you use tobacco products.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. You should not become pregnant or breast-feed while you are taking ponatinib. If you become pregnant while taking ponatinib, call your doctor immediately. Ponatinib may harm the fetus.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking ponatinib.
- you should know that your blood pressure may increase during your treatment with ponatinib. Your doctor will probably monitor your blood pressure during your treatment.
What SPECIAL DIETARY instructions should I follow?
Do not eat large amounts of grapefruit or drink grapefruit juice while taking this medication.
What should I do IF I FORGET to take a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What SIDE EFFECTS can this medicine cause?
Ponatinib may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- dry skin
- white patches or sores on the lips or in the mouth and throat
- loss of appetite
- weight loss
- difficulty falling asleep or staying asleep
- night sweats
- muscle cramps
- back, bone, joint, limb, or muscle pain
- pain, burning, numbness, or tingling in the hands or feet
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, stop taking ponatinib and call your doctor immediately or get emergency medical treatment:
- unusual bruising or bleeding
- black and tarry stools
- red blood in stools
- blood in the urine
- bloody vomit
- vomit that looks like coffee grounds
- frequent nose bleeds
- fever, sore throat, chills, or other signs of infection
- extreme tiredness or weakness
- weight gain
- swelling of hands, ankles, feet, or face
- pain, swelling, or tenderness in the abdomen (stomach area)
- ongoing pain that begins in the stomach area, but may spread to the back
Ponatinib may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
What should I know about STORAGE and DISPOSAL of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
What should I do in case of OVERDOSE?
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include:
- fever, sore throat, chills, and other signs of infection
- rapid, irregular, or pounding heartbeat
- chest pain
What OTHER INFORMATION should I know?
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: October 15, 2013.