Treatment Name: Ponatinib (Iclusig®)
Ponatinib (Iclusig®) is a Chemotherapy Regimen for Acute Lymphoid Leukemia (ALL)
How does Ponatinib work?
Ponatinib is designed to stop cancerous white blood cells from growing and dividing. A mutation (a problem with DNA) such as the "T315I mutation" can cause other therapies such as imatinib, dasatinib, nilotinib, and bosutinib to no longer work. However, ponatinib works on most mutations found in Philadelphia positive (Ph+) Acute Lymphoid Leukemia (ALL) cells.
Goals of therapy:
Ponatinib is taken to reduce symptoms from ALL or prevent them from ever occurring, but ponatinib is not commonly given with the goal of cure
How is ponatinib therapy for ALL taken?
- Usual starting dose: Ponatinib 45 mg oral tablet by mouth once Daily, every day
Currently, ponatinib is dispensed by a single pharmacy known as Biologics Pharmacy via the Ariad Pass program. Once it is received, it is taken at home.
Some patients may require hospitalization when initially diagnosed and begin treatment with ponatinib before leaving the hospital. Ponatinib is usually taken until it no longer works or until unaccpetable side effects occur.
It is important that you do not miss doses, unless your doctor specifically says that this is okay. Missing doses may prevent you from achieving a response and increase the risk of ponatinib no longer working.
Note: Individual doses may vary based upon your Doctor's recommendation, or drug availability
What are the most common side effets from ponatinib (Iclusig®) for ALL?
In clinical studies, the most commonly reported ponatinib side effects are shown here:
- Dry skin (22%)
- Skin rash (19%)
- Stomach pain (19%)
- Constipation (19%)
- Low red blood cells [anemia] (16%)
- Headache (12%)
- Low white blood cells [neutropenia] (12%)
- Increased blood lipase [sign of injury to pancreas] (9%)
- Fatigue (9%)
- Low platelets [thrombocytopenia] (9%)
- Muscle pain (6%)
- Neutropenic fever (6%)
- Joint pain (3%)
- Nausea (3%)
- Increased liver enzyme level in blood [sign of liver injury] (3%)
- Increased blood amylase [sign of injury to pancreas] (3%)
Some of the side effects listed may be due to ALL, rather than ponatinib. Therefore, some of these side effects may go away with continued treatment. Potential severe side effects include abdominal pain, pancreatitis, blood vessel narrowing, or vision problems.
Dose reductions are required in 55% of patients and roughly 2 out of 3 patients have to interrupt ponatinib therapy due to side effects or low blood cell counts. It is important that you tell your doctor about any side effects you are having so that they can adjust the dose if needed.
The percentage of patients that stopped using ponatinib in clinical studies due to unacceptable side effects was about 6%.
Importantly, not all people who experience a side effect from ponatinib will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid treatment with a certain medication altogether.
Side effects may be treatable when they occur or preventable by taking certain medications before they happen. When medications are taken to prevent a problem, this is known as prophylaxis, or "prophy" for short.
After starting treatment with ponatinib, be sure to come back and watch all of the side effect videos shown below. Each of these videos contain valuable information about side effect management that will hopefully help you to both feel better and stay out of the hospital.
Watch videos on common ponatinib therapy side effects below
Side effect videos
PainConstipationAnemiaFatigue Neutropenic FeverNausea and Vomiting
How often is monitoring needed?
Labs (blood tests) may be checked before treatment, once weekly during the first month, then every other week during the 2nd and 3rd month, then until stable. Labs at diagnosis often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), Lactate Dehydrogenase (LDH), magnesium, phosphate, and uric acid, plus any others your doctor may order. Tumor lysis syndrome is usually not seen after the first two weeks of therapy.
Additionally, your doctor will order a test known as BCR/ABL. Your doctor uses the BCR/ABL percentage (%) to monitor your response to ponatinib.
How often is imaging needed?
Imaging may be checked before treatment, and periodically thereafter. Imaging may include: a chest x-ray, or CT scan of the lungs. These are most often done to look for an infection causing pneumonia.
How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue the same dose of ponatinib, interrupt ponatinib therapy for a short period of time (usually several days; sometimes longer), decrease the dose, or switch therapy if goals of therapy are not being met.
Questions to Ask Your...
A better understanding of your treatments will allow you to ask more questions of your healthcare team. We then hope that with the answers, you will get better results and have greater satisfaction with your care. Because we know it's not always easy to know what questions to ask, we've tried to make it easy for you!
Choose any healthcare provider below to see common questions that you may want to ask of this person. Then, either print each list to bring to your clinic visits, or copy the questions and send them as a message to your healthcare team through your electronic medical record.
- A daily baby aspirin (81 mg) may be recommended to take with ponatinib to prevent unwanted blood clots, as long as your platelet count remains above 50 k/µL
- Ponatinib can be taken with food to avoid or decrease nausea
- Daily weight should be monitored when beginning therapy with ponatinib. This will help determine if swelling in the legs needs to be treated with diuretics. Bring a journal with these daily weight recordings to each clinic visit
- Patients should keep a journal of blood pressure readings at home and bring the results to each clinic visit for doctors to evaluate. Patients with high blood pressure may need a new blood pressure medication or existing medications adjusted
- Although rash is common, it is rarely severe. When rash occurs, it usually appears on the forearms, chest, abdominal area, and occasionally on the face. In most cases, therapy with ponatinib can be continued and the rash will go away on its own or with topical creams or lotions recommended by your doctor
- Ponatinib may cause your triglycerides to increase. A simple blood test to monitor triglyceride levels is sometimes performed before starting and repeated after several weeks to determine if the triglycerides are increasing. Fish oil supplements, which are rich in Omega-3 fatty acids, may be recommended to decrease triglyceride levels
- A chemical in grapefruit juice, starfruit, and pomegranate can decrease the body’s ability to break down ponatinib and increase the amount of ponatinib in your body. This may lead to an an increase in side effects, therefore it is best to avoid grapefruit, starfruit, and pomegranate while taking ponatinib
- Bring all of your pill bottles to every clinic visit! This will make it easier for your healthcare team to make sure that ponatinib can be taken safely with every other medication you are taking. A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
- If you are having trouble paying for ponatinib, there are many patient assistance programs available to help. Ask your doctor or pharmacist to help you with this before you run out!
- Clinical trials may exist for CML. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications
Patient Assistance & Co-payment Coverage
Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Ponatinib (Iclusig®), we have provided links that may help.
Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Ponatinib (Iclusig®). Depending upon your income, they may be able to help cover the cost of:
For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.
- If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.
Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Ponatinib (Iclusig®) and are the best source to help you understand drug cost.
- Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.
What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.
Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.
Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.
Learn more about pursuing emotional wellness while receiving treatment with Ponatinib (Iclusig®)
Individual Drug Label Information
- Ponatinib is an oral tablet that comes in either 15 mg, or 45 mg
- Ponatinib can be taken with or without food and with a large glass of water
- FDA boxed warnings include: Heart failure & Blood clots (which could cause heart attack, stroke)
- Liver problems
- If you miss a dose, and it is within 12 hours from the regular time you take it, you may still take it. If it is more than 12 hours late, skip it, and take the next scheduled dose at the regular time. Do not take two doses at the same time
- Ponatinib should be stored at room temperature
- Dosage adjustments may be required if good white blood cells (neutrophils), red blood cells, or platelets fall below the normal range
- Women of child-bearing potential should avoid becoming pregnant while taking ponatinib or taking ponatinib in the first trimester of pregnancy as it may harm the unborn baby. Women wanting to become pregnant should consult their doctor regarding the safest way to balance this with ponatinib therapy
- May interact with a steroid known as dexamethasone (Decadron), or a variety of anti-seizure medicines. A dosage increase is sometimes required to avoid losing response to ponatinib
- A chemical in grapefruit juice decreases the body’s ability to break down ponatinib so it is best to avoid grapefruit and grapefruit juice to help prevent an increase in side effects
- Low platelet count
- Rash or Dry skin
- Abdominal pain
- Muscle or Joint pain
- Nausea Low red blood cell count (Anemia)
- Pancreatitis Blood clots in arteries or veins
- High blood pressure
- Heart failure
- Liver problems
- Fever may be a sign of infection. Keep a thermometer at home and report any fevers immediately
- Click on the ponatinib (Iclusig) package insert below for reported side effects and possible drug interactions
Side Effect Videos
See DailyMed package insert.
Nausea and VomitingFatigue BleedingConstipationPainAnemiaBlood Clots
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1.) Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia-chromosome positive leukemias. N Engl J Med. 2013;369:1783-1796.
Created: April 7, 2020 Updated: April 7, 2020
What is Acute Lymphoid Leukemia (ALL)?
Acute Lymphoid Leukemia (ALL), also known as acute lymphoblastic leukemia, is a disease of the lymphoid cells found in the bone marrow. Lymphoid cells are responsible for developing into cells of the immune system called B-cells, T-cells, or Natural Killer cells. In ALL, immature lymphoid cells know as "blasts" replicate at a very fast rate. Sometimes blasts crowd out the normal cells in the bone marrow so that red blood cells or platelets are unable to develop.
Common symptoms of ALL include fatigue, infection, and bruising or bleeding. ALL is the most common cancer diagnosed in children, but is rare in adults. Most cases of ALL are considered "de novo" meaning that the cause is unknown; however, some cases can be linked to certain genetic syndromes. There is no staging system for ALL. Chromosomes are often analyzed to determine which mutations in the chromosomes exist. The effectiveness of the treatment may depend upon the specific chromosome mutations that are present.
NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose your therapy.
What is Chronic Phase?
When a patient with CML has a bone marrow biopsy that shows less than 10% blasts, they are said to be in chronic phase. Patients in chronic phase have few or no symptoms from CML.
What is Accelerated Phase?
When a patient with CML has a bone marrow biopsy that shows between than 11 – 20% blasts, they are said to be in accelerated phase. Patients with accelerated phase usually have symptoms such as poor appetite, weight loss, an enlarged spleen, or fever.
What is Blast Phase?
When a patient with CML has a bone marrow biopsy that shows more than 20% blasts, they are said to be in blast phase, or blast crisis. Patients with blast phase usually have symptoms similar to acute leukemia such as: easy bruising or bleeding, fever, poor appetite, weight loss, or an enlarged spleen.
If you are interested in reading the clinical trial results, please click on the references below:
1) Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia-chromosome positive leukemias. N Engl J Med. 2013;369:1783-1796.
2) Daily Med: Ponatinib Drug Label Information
What is BCR/ABL?
A gene mutation within CML cells. The percent of cells that have the BCR/ABL mutation goes down by taking ponatinib therapy. The goal is that the percentage will become undetectable. This happens in the many patients and is known as a complete molecular response, or 0.000%. At diagnosis, the BCR/ABL % is often very high, sometimes exceeding 100%. This is because the test is based upon the average BCR/ABL% from patients in one of the earliest clinical studies with imatinib. Having a BCR/ABL% greater than 100% at diagnosis does not usually affect the response to ponatinib.
Responding to Ponatinib?
The optimal response to ponatinib depends upon how long you have been taking it for. Ultimately, the goal is an undetectable BCR/ABL%, or 0.0000%, but a level less 1% usually predicts long-term survival as well. Patients who have a BCR/ABL of 10% or more after 3 months of ponatinib (without missing doses) may need to switch therapy to another medication that treats CML.
Goal BCR/ABL% (International Scale, IS) while taking Ponatinib therapy:
- Newly Diagnosed (No Ponatinib therapy): Variable [~80 - more than 100%]
- Complete Hematologic Response (CHR): Less than 10%
- Complete Cytogenetic Response (CCyR): Less than 1%
- Major Molecular Response (MMR): Less than 0.1%
- Complete Molecular Response (CMR): 0.0000%
What are diuretics?
Diuretics are medicines used to make people urinate. They are usually taken to help get rid of excess water that the body is holding onto. Excess water weight usually appears as swelling in the extremities such as arms, legs, or feet. It can occur in other areas such as in the lungs or around the eyes.
What is Tumor Lysis Syndrome?
Tumor lysis syndrome occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.
What is a CBC?
A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.
2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.
3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.
What is a CMP?
A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status, 2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.
Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein
13) Serum glucose
14) Serum calcium
What does "cure" mean?
The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, doctors use the word “remission” more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.
Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.
What is the "Ariad Pass" Program?
The makers of ponatinib, Ariad pharmaceuticals, provide a service known as the "Ariad Pass" program. Healthcare providers use this website to send in prescriptions for ponatinib. Once received, Biologics pharmacy works with patients' insurance and patient assistance foundations to dispense ponatinib at the lowest cost to patients.
When the medication is approved, Biologics pharmacy will contact you for counseling, to collect a co-pay (if any), to answer questions, and to verify your shipping address. Addiitonally, Biologics pharmacy may contact you before each refill to verify that your dose and shipping address have not changed, in addition to asking if you have side effects.
Click on our link if you are a healthcare provider wishing to write a prescription for ponatinib.