Iclusig (Ponatinib) - Oral

Warning:

Iclusig (ponatinib) has a boxed warning due to its potential to cause serious health problems. Blood clots can occur, which can happen in either the veins or arteries of the body and can lead to problems such as heart attack or stroke. 

Additional heart side effects included heart failure and an accumulation of fluid in the body. 

Severe liver injury also occurred in some people who took Iclusig.

What Is Iclusig?

Iclusig (ponatinib) is a medication in the class of tyrosine kinase inhibitors (TKIs) used to treat certain types of chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

TKIs are a type of targeted therapy often used in cancer treatment. Iclusig works by targeting and blocking the activity of several tyrosine kinases, which are proteins that promote cell growth, on the surface of cancer cells.

Iclusig comes in tablet form for oral use.

Drug Facts

Generic Name: Ponatinib

Brand Name(s): Iclusig

Drug Availability: Prescription

Therapeutic Classification: Tyrosine kinase inhibitor (TKI)

Available Generically: No

Controlled Substance: N/A

Administration Route: Oral

Active Ingredient: Ponatinib

Dosage Form(s): Tablets

What Is Iclusig Used For?

The Food and Drug Administration (FDA) approved Iclusig for use in adults for four indications:

  • Chronic phase CML in which at least two other TKIs have become resistant or were not tolerated
  • Accelerated or blast phase CML or Philadephia chromosome-positive (Ph+) CML where no other TKIs are appropriate for use
  • T315I-positive CML
  • T315I-positive Ph+ ALL

Iclusig is not approved to treat newly diagnosed chronic phase CML.

How to Take Iclusig

Iclusig is usually taken once a day around the same time each day. You can take it with or without food, but do not crush, chew, or break the tablets. Swallow the tablet whole. Avoid taking grapefruit products, such as grapefruit juice, while taking Iclusig. Grapefruit may increase exposure to the medication, which can result in side effects.

Storage

Store Iclusig at room temperature (68 F to 77 F) and keep the tablets in their original packaging.

What Are the Side Effects of Iclusig?

This is not a complete list of side effects and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Common Side Effects

The most common side effects experienced when taking Iclusig include:

  • Joint pain
  • Rash or dry skin
  • Headache
  • Constipation
  • Feeling tired
  • Nausea
  • Elevated blood pressure (hypertension)
  • Swelling in the hands, ankles, or body
  • Bleeding
  • Blood clots
  • Liver problems
  • Inflammation of the pancreas (pancreatitis)

The most common lab abnormalities associated with Iclusig include low red blood cell (anemia), low platelet, and low white blood cell counts.

Severe Side Effects

More serious or severe side effects can happen when taking Iclusig. Call your healthcare provider immediately if you’re having serious side effects, or call 911 if you feel your symptoms are life-threatening. Serious side effects and symptoms can include the following:

  • Blood clots: Chest pain, stroke symptoms, leg swelling, and severe abdominal pain
  • Heart failure or irregular heart rate: Swelling, shortness of breath, and palpitations
  • Liver problems: Yellowing of the eyes or skin (jaundice), bleeding, bruising, and abdominal pain
  • High blood pressure: Dizziness, headaches, chest pain, and confusion
  • Pancreas inflammation: Stomach pain, nausea, and vomiting
  • Neuropathy (nerve damage or impairment): Numbness or tingling in the hands or feet, vision problems, drooping of the face or eyelid, and taste changes
  • Eye problems: Bleeding in the eye, blurred vision, dryness, light flashes, itchiness, pain, and swelling
  • Bleeding: Vomiting or coughing up blood, significant bruising, frequent nose bleeds, blood in the urine or stool, and heavy menstrual bleeding
  • Fluid retention (edema): Swollen arms, legs, or face; shortness of breath; and cough
  • Irregular heartbeat: Palpitations, chest pain, and dizziness
  • Wound healing problems
  • Tear in stomach or intestine wall: Abdominal pain or swelling and fever
  • Reversible posterior leukoencephalopathy syndrome: Confusion, seizures, headaches, and vision changes

Report Side Effects

Iclusig may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Iclusig Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

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.

Modifications

Dosage adjustments may be necessary for:

  • Side effects: If you experience side effects, your healthcare provider may adjust your dose of the medication, depending on the severity of the side effect.
  • Liver impairment: If you have pre-existing liver disease, your healthcare provider may reduce the starting dose of Iclusig.
  • Breastfeeding: Do not breastfeed during treatment with ponatinib. Wait for six days following the last dose to start breastfeeding.
  • Interacting medications: The dose may also need to be modified if you take other medications that can interact with Iclusib.

Iclusic can cause fetal harm if taken during pregnancy. If you are of reproductive potential, using effective contraception during treatment is recommended. Contact your healthcare provider immediately if you become pregnant.

Missed Dose

If a dose of Iclusig is missed, it needs to be skipped and taken the next day at the usual scheduled time. The dose should never be doubled to make up for a missed dose.

Overdose: What Happens If I Take Too Much Iclusig?

If you take too much Iclusig, notify your healthcare provider and seek medical attention immediately. You may need to be monitored by a medical professional and receive supportive treatment.

What Happens If I Overdose on Iclusig?

If you think you or someone else may have overdosed on Iclusig, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Iclusig, call 911 immediately.

Precautions

Drug Content Provided and Reviewed by IBM Micromedex®

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.

What Are Reasons I Shouldn’t Take Iclusig?

Do not take Iclusig if you:

  • Are pregnant or breastfeeding
  • Are lactose intolerant, as it contains lactose
  • Surgery is planned within the same week

What Other Medications Interact With Iclusig?

When taken together, other medications may affect how Iclusig works and vice versa.

Drugs known as strong cytochrome P450 3A (CYP3A) inhibitors can increase concentrations of Iclusig in the blood, which may result in adverse reactions. Ketoconazole and grapefruit juice are examples of potent CYP3A inhibitors.

Additionally, strong CYP3A inducers can decrease concentrations of Iclusig, thereby reducing the Iclusig's efficacy. These include:

This is not a complete list of drug interactions that can occur with Iclusig. Share all your medications, including OTC and prescription products, vitamins, and herbal supplements, with your healthcare provider.

What Medications Are Similar?

There are other medications in the same class as Iclusig, which are used to treat CML. These medications include:

  • Gleevec (imatinib)
  • Tasigna (nilotinib)
  • Bosulif (bosutinib)
  • Sprycel (dasatinib)

Frequently Asked Questions

  • What is Iclusig used for?

    Iclusig (ponatinib) is used to treat adults with certain types of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL).

  • What are the side effects of Iclusig?

    Side effects associated with Iclusig can include:

    • Fatigue
    • Skin rash or dry skin
    • Nausea
    • Heart problems
    • Constipation
    • High blood pressure
    • Inflammation of the pancreas
    • Blood clots
    • Liver problems
  • What interactions can occur with Iclusig?

    Iclusig can interact with drugs known as strong CYP3A inhibitors and inducers. Potent CYP2A inhibitors include ketoconazole and grapefruit juice; these substances can increase the risk of side effects when taken with Iclusig. CYP3A inducers include medications such as phenytoin and rifampin; these drugs can reduce how well Iclusig works.

How Can I Stay Healthy While Taking Iclusig?

Taking care of yourself when you have CML or ALL is very important. Taking Iclusig as prescribed is a critical component of your treatment.

While taking this medication, follow all the instructions given to you by your healthcare provider. It can be scary or overwhelming to start a new cancer treatment, especially due to the potential side effects. Talk to your oncology team about what to expect and contact them if you start experiencing any adverse effects.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Takeda. Highlights of prescribing information.

  2. UpToDate. Cytochrome P450 3A (including 3A4) inhibitors and inducers.

  3. American Cancer Society. Targeted therapies for chronic myeloid leukemia.

By Julie Scott, MSN, ANP-BC, AOCNP
Julie is an Adult Nurse Practitioner with oncology certification and a healthcare freelance writer with an interest in educating patients and the healthcare community.