Trade Name: ICLUSIG®

Generic Name: Ponatinib

ICLUSIG® is the trade name for the generic drug ponatinib. In some cases, health care professionals may use the generic name ponatinib when referring to the trade name ICLUSIG®.

Drug Type:

ICLUSIG® is a targeted therapy. ICLUSIG® is classified as a Tyrosine Kinase inhibitor; Vascular Endothelial Growth Factor (VEGF) inhibitor. (For more detail, see "How this drug works," below.)

What ICLUSIG® Is Used For:

• ICLUSIG® is used to treat chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL).

Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How ICLUSIG® Is Given:

• ICLUSIG® is a pill, taken by mouth.
• Take ICLUSIG® with or without food.

• You should not drink grapefruit juice or eat grapefruit during treatment with ICLUSIG®. It may change the amount of ICLUSIG® in your blood.
• Take ICLUSIG® exactly as prescribed.
• Swallow ICLUSIG® tablets whole with at least 8 ounces of water. Do not crush or dissolve tablets.
• Do not change your dose or stop ICLUSIG® unless your health care provider tells you to.

If you miss a dose and your next dose is due in:

• Less than 12 hours, take your next dose at the normal time. Do not make up the next dose.
• 12 hours or more, take the missed dose as soon as you remember. Take your next dose at the normal time.

• Do not take more than 1 dose of ICLUSIG® at one time. Call your health care provider right away if you take too much.

• The amount of ICLUSIG® that you will receive depends on many factors, including your general health or other health problems, and the type of cancer or condition you have. Your doctor will determine your exact ICLUSIG® dosage and schedule.

Side Effects:

Important things to remember about the side effects of ICLUSIG®:

• Most people will not experience all of the ICLUSIG® side effects listed.
• ICLUSIG® side effects are often predictable in terms of their onset, duration, and severity.
• ICLUSIG® side effects are almost always reversible and will go away after therapy is complete.
• ICLUSIG® side effects may be quite manageable. There are many options to minimize or prevent the side effects of ICLUSIG®.

The following side effects are common (occurring in greater than 30%) for patients taking ICLUSIG®:

• High blood pressure
• Neutropenia
• Leukopenia
• Blood sugar increased
• Low platelets
• Phosphorous decreased
• Anemia
• Rash
• Increased liver enzymes ALT/AST
• Calcium decreased
• Abdominal pain
• Constipation
• Fatigue or weakness
• Headache
• Dry skin
• Fever
• Nausea
• Appetite decreased
• Joint pain

These are less common side effects (occurring in 10-29%) for patients receiving ICLUSIG®:

• Sodium decreased
• Albumin decreased
• Diarrhea
• Neutropenic fever
• Blood sugar decreased
• Increased bleeding
• Vomiting
• Mouth sores
• Muscle aches
• Swelling
• Infection
• Shortness of breath
• Bilirubin increased
• Pleural effusion
• Cough
• Potassium decreased
• Pain
• Potassium increased
• Heart failure
• Chills
• Weight loss
• Peripheral neuropathy
• Muscle spasms
• Pneumonia
• Arterial ischemia
• Bone pain
• Insomnia
• Upper respiratory infection
• Urinary tract infection
• Cellulitis (skin infection)
• Bicarbonate decreased
• Dizziness

Rare but serious possible side effects of ICLUSIG®:

• This drug may raise your chance of having blood clots, a stroke or a heart attack. Talk with your doctor about this risk.

Not all side effects are listed above. Some that are rare (occurring in less than about 10 percent of patients) are not listed here. Always inform your health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:

Seek emergency help immediately and notify your health care provider, if you experience the following symptoms:

• Chest pain, shortness of breath, weakness on one side of the body, speech problems, leg pain, or leg swelling

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100.4° F (38° C or higher, chills)
• Unusual bleeding
• Black or tarry stools, or blood in your stools

The following symptoms require medical attention, but are not an emergency. Contact your doctor or health care provider within 24 hours of noticing any of the following:

• Hypertension (systolic BP > 150 (top number) or diastolic BP > 90 (bottom number)
• Diarrhea (4-6 episodes in a 24-hour period).

• Nausea (interferes with ability to eat and unrelieved with prescribed medication).
• Vomiting (vomiting more than 4-5 times in a 24 hour period).
• Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decrease amount of urine, or dizziness.
• Skin or the whites of your eyes turn yellow
• Urine turns dark or brown (tea color)
• Decreased appetite
• Pain on the right side of your stomach
• Bleed or bruise more easily than normal
• Itching
• Cough with or without mucus
• Mouth sores
• Pain or burning with urination
• Extreme fatigue (unable to carry on self-care activities)

Always inform your doctor or health care provider if you experience any unusual symptoms.

Precautions:

• Before starting ICLUSIG® treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). While taking ICLUSIG®, ask your doctor before you take aspirin or products containing aspirin.
• While taking ICLUSIG®, do not receive any kind of immunization or vaccination without your doctor’s approval.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus.)
• For both men and women: Use contraceptives and do not conceive a child (get pregnant) while taking ICLUSIG®. Barrier methods of contraception such as condoms are recommended.
• Do not breast feed while taking ICLUSIG®.

Self-Care Tips:

• While taking ICLUSIG®, drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• Wash your hands often and after taking each dose of ICLUSIG®.
• You may be at risk of infection so try to avoid crowds or people with colds, and report fever or any other signs of infection immediately to your health care provider.
• Monitor your blood pressure and notify your physician if blood pressure is elevated or if you develop severe headache, light headedness or other neurological symptoms (numbness, tingling, difficulty speaking).
• To help treat/prevent mouth sores while taking ICLUSIG®, use a soft toothbrush, and rinse three times a day with 1 teaspoon of baking soda mixed with 8 ounces of water.
• Use an electric razor and a soft toothbrush to minimize bleeding.
• Avoid contact sports or activities that could cause injury.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals while taking ICLUSIG®.
• Follow regimen of anti-diarrhea medication as prescribed by your health care professional.
• Eat foods that may help reduce diarrhea (see managing side effects - diarrhea ).
• Avoid sun exposure. Wear SPF 15 (or higher) sunblock and protective clothing. ICLUSIG® may make you more sensitive to the sun and you may sunburn more easily.
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely while you are taking ICLUSIG®. You should discuss this with your doctor.
• Get plenty of rest.
• Maintain good nutrition while being treated with ICLUSIG®.
• If you experience symptoms or side effects while being treated with ICLUSIG®, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing:

You will be checked regularly by your doctor while you are taking ICLUSIG® to monitor side effects and check your response to therapy. Periodic blood work will be obtained to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver). Your blood pressure will be monitored closely.

How ICLUSIG® Works:

ICLUSIG® is not a chemotherapy drug but one of many "targeted therapies." Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells. To date, cancer treatment has focused primarily on killing rapidly dividing cells because one feature of cancer cells is that divide rapidly. Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects.

Targeted therapy is about identifying other features of cancer cells. Scientists look for specific differences in the cancer cells and the normal cells. This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects. Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells.

There are different types of targeted therapies, defined in three broad categories. Some targeted therapies focus on the internal components and function of the cancer cell. The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die. There are several types of targeted therapy that focus on the inner parts of the cells. Other targeted therapies target receptors that are on the outside of the cell. Therapies that target receptors are also known as monoclonal antibodies. Antiangiogenesis inhibitors target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.

ICLUSIG® is designed to block tumor cell growth in several ways. ICLUSIG® targets several proteins (called tyrosine kinases) on the surface of cancer cells, as well as targets within the cell. Several of these targets are thought to be involved in angiogenesis (making of blood vessels). By blocking these targets, it is hoped the cancer will shrink.

Research continues to identify which cancers may be best treated with targeted therapies and to identify additional targets for more types of cancer.

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this web site is meant to be helpful and educational, but is not a substitute for medical advice.

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