Pronunciation:

poe-NA-ti-nib

Brand Names:

• Iclusig

Dosage Forms:

• Tablet

Warnings:

Arterial Occlusion Events, Venous Thromboembolic Events, Heart Failure, and HepatotoxicityArterial occlusive events (AOEs), including fatalities, have occurred in ponatinib hydrochloride-treated patients. AOEs included 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 age 50 years or younger, experienced these events. Monitor for evidence of AOEs. Interrupt or discontinue ponatinib hydrochloride based on severity. Consider benefit-risk to guide a decision to restart ponatinib hydrochloride.Venous thromboembolic events (VTEs) have occurred in ponatinib hydrochloride-treated patients. Monitor for evidence of VTEs. Interrupt or discontinue ponatinib hydrochloride based on severity.Heart failure, including fatalities, occurred in ponatinib hydrochloride-treated patients. Monitor for heart failure and manage patients as clinically indicated. Interrupt or discontinue ponatinib hydrochloride for new or worsening heart failure.Hepatotoxicity, liver failure and death have occurred in ponatinib hydrochloride-treated patients. Monitor liver function tests. Interrupt or discontinue ponatinib hydrochloride based on severity .

Classifications:

Therapeutic—

Antineoplastic Agent

Pharmacologic—

Tyrosine Kinase Inhibitor

Uses of This Medicine:

Ponatinib is used to treat chronic phase chronic myeloid leukemia (CML) in patients who have used at least 2 other treatments that did not work well. This medicine is also used to treat accelerated phase or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in patients who cannot receive any other medicine. It is also used to treat chronic phase, accelerated phase, or blast phase CML or Ph+ ALL in patients who have a specific type of abnormal gene (T315l-positive). Leukemia is a type of cancer where the body makes abnormal white blood cells.

Ponatinib is an antineoplastic (cancer) medicine. It interferes with the growth of cancer cells, which are eventually destroyed by the body. Since the growth of normal cells may also be affected by ponatinib, other side effects can occur. Before you begin treatment, talk to your doctor about the benefits of this medicine as well as the possible risks of using it.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of ponatinib in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ponatinib in the elderly. However, elderly patients are more likely to have unwanted effects (eg, decreased appetite, extra fluid, muscle spasms, trouble breathing), which may require caution and an adjustment in the dose for patients receiving ponatinib.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine, Live
• Zoster Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine
• Apalutamide
• Atazanavir
• Bacillus of Calmette and Guerin Vaccine, Live
• Boceprevir
• Carbamazepine
• Ceritinib
• Cholera Vaccine, Live
• Clarithromycin
• Cobicistat
• Conivaptan
• Dengue Tetravalent Vaccine, Live
• Enzalutamide
• Fosphenytoin
• Idelalisib
• Indinavir
• Influenza Virus Vaccine, Live
• Itraconazole
• Ketoconazole
• Lopinavir
• Lumacaftor
• Mitotane
• Nefazodone
• Nelfinavir
• Phenytoin
• Poliovirus Vaccine, Live
• Posaconazole
• Rifampin
• Ritonavir
• Saquinavir
• Smallpox Vaccine
• St John's Wort
• Telaprevir
• Telithromycin
• Tipranavir
• Typhoid Vaccine, Live
• Voriconazole
• Yellow Fever Vaccine

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, history of or
• Anemia (low red blood cells) or
• Bleeding problems or
• Blood clotting problems or
• Congestive heart failure or
• Heart rhythm problems (eg, arrhythmia) or
• Hypertension (high blood pressure) or
• Hyperuricemia (high uric acid in the blood) or
• Liver disease or
• Neutropenia (low white blood cells) or
• Pancreatitis, history of or
• Stomach or bowel problems (eg, fistula, perforation) or
• Thrombocytopenia (low platelets in the blood)—Use with caution. May make these conditions worse.

• Diabetes or
• Heart attack, history of or
• Heart or blood vessel disease or
• Hyperlipidemia (high cholesterol or fats in the blood) or
• Stroke, history of—May cause side effects to become worse.

• Lactose intolerance (stomach problem)—The tablet contains lactose, which can make this condition worse.

Proper Use of This Medicine:

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance for unwanted effects.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Take this medicine with or without food. Swallow the tablet whole. Do not crush, break, chew, or dissolve it.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit and grapefruit juice may cause the blood levels of this medicine to be higher than normal.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treatment of leukemia:
    • Adults—At first, 45 milligrams (mg) once a day. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. If you are a woman who can get pregnant, your doctor may do tests to make sure you are not pregnant before starting treatment. Use a highly effective form of birth control to keep from getting pregnant during treatment and for 3 weeks after your last dose of this medicine. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may cause blood clotting problems. Check with your doctor right away if you have chest pain, numbness or weakness in your arm, leg, or on one side of your body, trouble breathing, speech problems, or leg pain or swelling.

Check with your doctor right away if you have stomach pain, pale stools or dark urine, a loss of appetite, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause fluid retention and heart failure. Check with your doctor if you are rapidly gaining weight, have chest pain or discomfort, extreme tiredness or weakness, trouble breathing, or swelling of the hands, wrist, ankles, or feet. These may be symptoms of heart problems or too much water in your body.

Pancreatitis may occur with this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Check with your doctor immediately if you have vision changes, such as blurred vision, difficulty reading, or eye pain, dryness, irritation, or swelling, during treatment. Your doctor may want you to have your eyes checked by an eye doctor.

Check with your doctor right away if you are having decreased or increased sensitivity to pain or touch, or burning, numbness, tingling, or painful sensations in the arms, hands, legs, or feet. These could be symptoms of a nerve problem (eg, cranial or peripheral neuropathy).

Ponatinib can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may increase your chance of having blood clots or a brain condition called reversible posterior leukoencephalopathy syndrome (RPLS). Tell your doctor right away if you develop sudden and severe headaches, fainting spells, seizures, unusual drowsiness, confusion, or problems with vision, speech, or walking while you are using this medicine.

This medicine may cause a serious type of reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Call your doctor right away if you have a decrease or change in urine amount, joint pain, stiffness, or swelling, lower back, side, or stomach pain, a rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

This medicine may affect the way your body heals from cuts and wounds. Make sure any doctor who treats you knows that you are using this medicine. You might need to stop using this medicine several weeks before having surgery. If you have questions about this, talk to your doctor.

If you plan to have children, talk with your doctor before using this medicine. Some women using this medicine have become infertile (unable to have children).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bladder pain

bleeding gums

bloating or swelling of the face, arms, hands, lower legs, or feet

blurred vision

chest pain

chills

cloudy urine

confusion

constipation

cough or hoarseness

coughing up blood

decreased urine output

difficult, burning, or painful urination

difficulty with breathing or swallowing

dilated neck veins

dizziness

fainting

frequent urge to urinate

increased menstrual flow or vaginal bleeding

indigestion

irregular breathing

joint pain, stiffness, or swelling

lightheadedness

lower back, side, or stomach pain

nervousness

nosebleeds

pains in the chest, groin, or legs, especially calves of the legs

pains in the stomach, side, or abdomen, possibly radiating to the back

pale skin

paralysis

pinpoint red spots on the skin

pounding in the ears

prolonged bleeding from cuts

rapid weight gain

rapid, shallow breathing

red or black, tarry stools

red or dark brown urine

severe headaches of sudden onset

slow or fast heartbeat

sore throat

sudden loss of coordination

sudden slurred speech

sudden vision changes

tingling of the hands or feet

ulcers, sores, or white spots in the mouth

unusual bleeding or bruising

unusual weight gain or loss

Less common

Anxiety

burning, numbness, tingling, or painful sensations

chest discomfort

fast, pounding, or irregular heartbeat or pulse

pain, redness, or swelling in the arms or legs

unsteadiness or awkwardness

weakness in the arms, hands, legs, or feet

Incidence not known

Blistering, peeling, loosening of the skin

bloody, black, or tarry stools

blue-green halos seen around objects

clay-colored stools

dark urine

decreased appetite

diarrhea

dry eyes

fever

headache

heartburn

indigestion

itching or skin rash

joint or muscle pain

loss of appetite

nausea and vomiting

red irritated eyes

red skin lesions, often with a purple center

sensitivity of the eyes to light

sensitivity to heat

severe vomiting, sometimes with blood

sore throat

stomach cramps or tenderness

sweating

trouble sleeping

unusual tiredness or weakness

vomiting of material that looks like coffee grounds, severe and continuous

weight loss

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Back or bone pain

cracked lips

difficulty having a bowel movement (stool)

difficulty with moving

dryness, itching, pain, redness, swelling, tenderness, or warmth on the skin

lack or loss of strength

muscle aches, pain, or stiffness

stuffy or runny nose

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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