What Is Ponatinib?
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Ponatinib - Usage, Dosage, Side Effects, Drug Warnings, and Precautions

Published on Oct 10, 2022   -  11 min read


Ponatinib is a drug used to treat chronic myeloid leukemia. Read more about this drug below.


Ponatinib is an orally administered drug for treating chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This drug is considered a multi-targeted tyrosine kinase inhibitor as it is effective against mutations resistant to other therapeutic agents.

The United States Food and Drug Administration (US FDA) approved the drug in 2012 for treating patients with resistant CML and Ph+ ALL. From the results of the various studies conducted in 2016, Ponatinib gained approval for treating patients with accelerated phase, chronic phase, or blast phase CML and Ph+ ALL with no prior tyrosine kinase inhibitor therapy. In addition, approval for treatment against T315I-positive Ph+ ALL was also granted.

How Does Ponatinib Work?

Tyrosine kinases are proteins that stimulate cancer cells to grow. Ponatinib is a tyrosine kinase inhibitor that inhibits the action of these proteins and prevents the multiplication of cancer cells.


  • It is indicated for treating chronic myeloid leukemia patients in the chronic phase, accelerated phase, or blast phase, resistant to tyrosine kinase inhibitor therapy.

  • It is indicated for patients with acute lymphoblastic leukemia and positive for Philadelphia chromosomes, resistant to tyrosine kinase inhibitor therapy.


Ponatinib 15 mg or 45 mg can be administered orally once daily, with or without food. The physician can modify, interrupt, or stop the dose based on the hematologic and non-hematologic toxicity.


The following are the conditions and symptoms that the patients must be informed of before drug administration.

  • Blood Clots: Patients may have symptoms suggestive of a blood clot, such as chest pain, shortness of breath, speech problems, weakness of the body, or leg swelling.

  • Liver Problems: Patients are advised to report to the doctor immediately if they have symptoms of liver failure, such as yellowing of eyes and skin, tea-colored urine, and drowsiness.

  • Heart Problems: If the patients have signs and symptoms such as chest pain, shortness of breath, or palpitations, they must be monitored and treated accordingly.

  • High Blood Pressure: The patients are advised to inform the doctor if they have symptoms of high blood pressure, such as headache, dizziness, chest pain, or shortness of breath. In such instances, they must be monitored and treated accordingly.

  • Pancreatitis: The patients should consult the doctor if they have symptoms of nausea, vomiting, abdominal pain, or discomfort. In such cases, the physician will decide on alterations in drug administration.

  • Bleeding: The patients may encounter episodes of bleeding.

  • Fluid Retention: The patients must report to the doctor if they have weight gain, abdominal swelling, leg swelling, or shortness of breath.

  • Low Blood Cell Counts: The patients must report to the physician if they have a fever or other signs of infection indicating low blood cell counts.

  • Compromised Wound Healing: The patients should inform the physician if they have undergone surgery or planning to undergo surgery.

  • Harm to the Fetus: The patients must be informed that the drug can harm the fetus and are advised to avoid pregnancy during therapy.

For Patients:-

Know About Chronic Myeloid Leukemia:

Chronic myeloid leukemia (CML) is the cancer of blood-forming cells of the bone marrow. It is also called chronic myelogenous leukemia. A genetic change occurs in the immature red blood cells, white blood cells, and platelets, forming an abnormal gene called BCR-ABL (breakpoint cluster region-Abelson proto-oncogene), turning the blood cells into CML cells. These cells divide and spread to other body parts. This condition most commonly affects adults and is rare in children.

Learn More About Ponatinib:-

When and How Often to Take Ponatinib?

Ponatinib can be taken once daily with or without food. The commonly administered doses are 15 mg and 45 mg. However, the dose recommendations may depend on the patient's hematologic (blood-related) condition.

How Effective Is Ponatinib?

In a study including 267 patients, Ponatinib achieved 60 % major cytogenetic (study of chromosomes) response, 40 % major molecular response, and 25 % molecular response. The probability of maintaining a major cytogenetic response was 82 % among the patients who responded.

Things to Inform Your Doctor Before They Prescribe You Ponatinib:

Inform the doctor if you have the following conditions before the doctor prescribes you the medicine.

  • Cardiovascular disorders.

  • Respiratory problems.

  • Surgical procedure.

  • Severe bleeding.

  • Pregnant or planning to become pregnant.

  • Breastfeeding or planning to breastfeed.

  • Under medications or supplements.

Starting Ponatinib:-

How to Take Ponatinib?

Things to Do After You Start Taking Ponatinib:

After starting Ponatinib, schedule regular appointments with the doctor to conduct a physical and diagnostic test to detect abnormalities, based on the test results, the doctor will recommend dose continuation, reduction, elevation, or drug interruption.

Look Out for Side Effects:

After you start taking the drug, you may encounter certain side effects.

They are:

  • Abdominal pain.

  • Fever.

  • Headache.

  • Skin rash.

  • Tiredness.

  • Nausea.

  • Constipation.

  • Joint pain.

The side effects that require medical attention are:

  • Chest pain.

  • Pain spreading to the arm or shoulder.

  • Weakness of the body.

  • Rapid breathing.

  • Easy bruising.

  • Confusion.

  • Unusual bleeding.

  • Irregular heart rate.

  • Shortness of breath.

  • Yellowing skin.

  • Dysuria or anuria.

  • Weak pulse.

  • Overactive reflexes.

Dietary Alterations:

Ponatinib must not be taken with grapefruit juice as it can increase the risk of side effects of the drug.

What Should Be Done When You Miss a Dose?

When you miss a dose of Ponatinib, do not overdose. Instead, take the next dose according to the schedule. Any modifications in the dose must be recommended by the physician only.

What Should Be Done to Treat Ponatinib Overdose?

Overdose of Ponatinib can cause chest pain, pneumonia, atrial fibrillation (a condition characterized by a rapid heart rate that leads to blood clots in the heart), pericardial effusion (fluid accumulation in the space around the heart), and systemic inflammatory response (a set of physiological actions that fights infection). So, in case of an overdose, the patient has to be observed and provided supportive treatment.

How to Store Ponatinib?

Ponatinib tablets must be stored at 20 to 25 degree-Celsius in a closed container. The medications must be kept away from children and pets.

How to Handle Ponatinib?

The medication must be stored in a closed container and handled bare hands. Wash the hands before and after handling the medication.

How to Dispose of Ponatinib?

The expired or wasted medication must be discarded carefully. They must not be disposed of by flushing down the toilet or in the trash. Instead, the state-licensed medical waste contractor can be contacted to dispose of the drugs by burial in a landfill or incineration.

Avoid Self-Medication:

The tablet should not be taken for a condition that was not prescribed. And do not suggest the tablet to anyone with the same symptoms because the medication may show different effects in different individuals. Consult the physician, discuss with them, and then take medicine.

Staying On Ponatinib:-

Tips to Stay On Track:

To stay on track with the medicine:

  1. Take the drug as directed by the doctor.

  2. Do not miss a dose or overdose to compensate for a missed dose. If you do so, inform the physician immediately.

  3. In addition, schedule regular appointments with the physician to monitor the disease progression and recommend dose alteration.

For Doctors


  • It is indicated for treating chronic myeloid leukemia patients in the chronic phase, accelerated phase, or blast phase, resistant to tyrosine kinase inhibitor therapy.

  • It is indicated for patients with acute lymphoblastic leukemia and positive for Philadelphia chromosomes, resistant to tyrosine kinase inhibitor therapy.


Mechanism of Action:

Ponatinib is a tyrosine kinase inhibitor. Its primary target is the BCR-ABL (breakpoint cluster region-Abelson proto-oncogene) tyrosine kinase, the activator of chronic myeloid leukemia. This tyrosine kinase is a protein formed by the fusion of BCL (breakpoint cluster region) and ABL (Abelson proto-oncogene) genes called the Philadelphia chromosome. Ponatinib is a unique drug that can treat resistant cases of CML because it blocks the activity of ABL and T315I mutant kinases.


The QTc interval is the measurement to assess the heart's electrical activity recorded in the electrocardiogram. The QT interval was assessed in patients who received 30 mg, 45 mg, and 60 mg Ponatinib orally daily. No significant changes in the QTc interval were observed.

Chemical Taxonomy:



Active Ingredient: Ponatinib Hydrochloride.

Inactive Ingredients: Inactive ingredients include lactose monohydrate, sodium starch glycolate (type B), microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. In addition, the tablet coating contains talc, polyvinyl alcohol, polyethylene glycol, and titanium dioxide.


  • The exact bioavailability of Ponatinib is unknown. However, its peak concentration is observed after six hours of drug administration.

  • The drug absorption is unaltered by food intake.

  • The aqueous solubility depends on the pH. If the pH is high, solubility is low.


  • The volume of distribution of Ponatinib is found to be 1223 L when administered 45 mg orally once daily for 28 days.

  • More than 99 % are bound to plasma proteins.


  • A study suggests that at least 64 % of the drug administered undergoes phase I and II metabolism.

  • Ponatinib also undergoes metabolism by esterases or amidases.


Ponatinib gets eliminated via urine and feces. When a single oral dose of Ponatinib is administered, about 87 % gets excreted in the feces and 5 % in the urine.


Ponatinib was not found to be mutagenic and clastogenic in vivo studies when administered 2000 mg/kg orally. However, it is found to have a negative effect on fertility through studies on monkeys. It showed degeneration of testicular epithelium in male monkeys and follicular atresia in female monkeys.

Warning and Precaution:

  • Arterial Thrombosis: The drug must be interrupted or discontinued if the patients develop arterial thrombotic events.

  • Hepatotoxicity: The liver function test must be taken monthly, and the drug has to be interrupted, discontinued, or reduced accordingly.

  • Congestive Heart Failure: The signs and symptoms must be monitored and treated promptly.

  • Hypertension: The patient's blood pressure must be monitored and treated accordingly.

  • Pancreatitis: The serum lipase levels are monitored monthly, and the drug is interrupted or discontinued as required.

  • Hemorrhage: The drug should be interrupted during severe hemorrhage.

  • Fluid Retention: The patients are monitored regularly, and the drug is interrupted, reduced, or discontinued in case of signs or symptoms pointing to fluid retention.

  • Cardiac Arrhythmias: The symptoms of arrhythmia must be monitored regularly.

  • Myelosuppression: The conditions such as anemia, neutropenia, and thrombocytopenia require dose reduction or interruption. Hence the blood counts are to be monitored every two weeks.

  • Tumor Lysis Syndrome: The patients should be hydrated and must correct high uric acid levels before Ponatinib therapy.

  • Compromised Wound Healing: The drug administration must be interrupted during surgical procedures.

  • Embryo-Fetal Toxicity: The drug can harm the fetus. Hence, Ponatinib administration must be avoided in pregnant women or planning to become pregnant.

Dosage and Forms:

  • Ponatinib is an orally administered drug.

  • It is a white, film-coated tablet.

  • The recommended dosages are 15 mg and 45 mg, based on the severity of the condition to be treated.

  • The drug dosage can also be modified based on drug interactions and disease progress.

Administration of the Drug:

  • Ponatinib should be taken once daily.

  • The drug can be taken orally.

  • The doses commonly recommended are 15 mg and 45 mg.

  • The drug can be taken with or without food.

  • The dose should be taken regularly and not skipped.

  • If missed, overdosing should be avoided.

Considerations for Administration:

  • The co-administration of Ponatinib with strong CYP3A inhibitors must be avoided as they increase the plasma concentration of Ponatinib and require dose reduction.

  • The co-administration of Ponatinib with drugs that elevate gastric pH must be avoided as they decrease the bioavailability of Ponatinib.

  • The administration of Ponatinib must also be avoided in patients with cardiovascular events or other systemic abnormalities.


The following are the conditions where Ponatinib is contraindicated.

  • Anemia.

  • Neutropenia.

  • Thrombocytopenia.

  • High blood pressure.

  • Arrhythmias.

  • Heart attack.

  • Stroke.

  • Arterial aneurysm.

  • Peripheral vascular disease.

  • Bleeding.

  • Hepatitis.

  • Pancreatitis.

  • Abnormal liver function tests.

  • Pregnancy.

  • Breastfeeding.

Clinical Studies for Acalabrutinib:

The safety and efficacy of Ponatinib in patients with chronic myeloid leukemia and acute lymphoblastic leukemia, whose disease was resistant to tyrosine kinase inhibitor therapy, were evaluated in an open-label multicenter trial.

  • Dose of Administration: 45 mg once daily.

Patients were divided into groups based on the disease phase, such as

  1. Chronic phase CML.

  2. Accelerated phase CML.

  3. Blast phase CML

  4. Resistant or intolerant to tyrosine kinase inhibitor therapy.

  5. Presence of T315I mutation.

Duration of treatment in different groups.

  1. Chronic phase CML - 281 days.

  2. Accelerated phase CML - 286 days.

  3. Blast phase CML - 89 days.

  • Follow-up was done for up to ten months.

  • The patients with chronic phase-chronic myeloid leukemia achieved a major hematologic response in 84 days.

  • The patients with acute phase and blast phase-chronic myeloid leukemia and Philadelphia positive-acute lymphoblastic leukemia achieved major hematologic response in 21, 29, and 20 days respectively.

Drug Interactions:

  • Strong Inhibitors of CYP3A (Cytochrome P450, Family 3, Subfamily A) Enzymes: When Ponatinib was coadministered with strong CYP3A inhibitors such as Ketoconazole, Itraconazole, Indinavir, Lopinavir, Nefazodone, Ritonavir, Telithromycin, and Voriconazole, the plasma concentration of Ponatinib were increased. Hence, the dosage of Ponatinib was reduced to 30 mg once daily when administered with the above drugs.

  • Strong Inducers of CYP3A Enzymes: The co-administration of Ponatinib with strong CYP3A has not been evaluated in clinical or in vitro trials. However, co-administration is considered only when the beneficial effects outweigh the risks.

  • Drugs That Elevate Gastric pH: When Ponatinib is coadministered with the drugs that elevate gastric pHs, such as H2 blockers, proton pump inhibitors, and antacids, the elevated pH can minimize the bioavailability of Ponatinib. Hence co-administration is usually avoided unless the beneficial effects outweigh the risks.

  • Drugs that Are Substrates of the BCRP: (Breast Cancer Resistance Protein) Transporter Systems: When Ponatinib is coadministered with the drugs that are substrates of BCRP transporter systems such as Methotrexate, Imatinib, Lapatinib, Sulfasalazine, and Rosuvastatin, Ponatinib inhibits those transporters. This is concluded in an in vitro study. No clinical treatment regarding this co-administration exists.

Other Specifications:-

Ponatinib in Pregnant Women:

There are no adequate studies on Ponatinib in pregnant women. However, studies on animals indicate that Ponatinib causes harm to the fetus. It can lead to reduced body weight, increased resorptions, multiple soft and skeletal alterations, and decreased ossification. So women are not recommended to become pregnant during Ponatinib intake or not take the drug during pregnancy.

Ponatinib in Lactating Women:

Ponatinib can get excreted in human milk. Hence, discontinuing breastfeeding or the drug should be decided, considering the drug therapy necessary for the mother.

Ponatinib in Pediatric Patients:

The administration of Ponatinib in pediatric patients has not been established yet.

Ponatinib in Geriatric Patients:

The administration of Ponatinib in geriatric patients can lead to adverse reactions such as decreased platelet count, decreased appetite, peripheral edema, dyspnea, and muscle spasms. Hence, the dose selection for elderly patients should be cautious to prevent hepatic, renal, and cardiac dysfunction.

Ponatinib in Renal Impairment Patients:

Renal excretion is not the route of Ponatinib elimination. Hence the administration of the drug in renal impairment patients is not yet determined.

Ponatinib in Hepatic Impairment Patients:

Hepatic elimination is the route for Ponatinib excretion, so the administration of Ponatinib is avoided in patients with moderate to severe hepatic impairment as it can lead to excessive exposure to the drug. In addition, it can also lead to severe adverse reactions.

Frequently Asked Questions


Is Ponatinib Used for Chemotherapy?

Ponatinib is a chemotherapy regimen for acute lymphoid leukemia (ALL). In addition, it is one of the targeted therapy drugs which can act on targeted tumor cells in the body, leaving behind the normal, unaffected cells.


What Is the Drug Type of Ponatinib?

Ponatinib is a protein tyrosine kinase inhibitor. It blocks and prevents the activation of tyrosine kinase proteins responsible for stimulating cancer cells to grow. In addition, the drug acts on various tyrosine kinase proteins and is called a multi-kinase inhibitor.


Is Weight Gain a Possible Drawback of Ponatinib?

Ponatinib commonly results in fluid retention, which may cause weight gain, posing symptoms of heart problems, such as chest pain, weakness, difficulty breathing, and swelling of the extremities. Hence, it is crucial to consult a physician if weight gain is noted after taking Ponatinib.


Which Generation Does Ponatinib Belong To?

Ponatinib is a third-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CLL). The primary characteristics of these third-generation inhibitors are that they are mutant-selective and show more significant activity toward EGFR (epidermal growth factor receptor) mutant cells than EGFR wild-type cells.


Is Ponatinib an Effective Drug?

Ponatinib has a considerable effect against native and mutant  BCR-ABL1, which is the combination of the genes BCR and ABL. In addition, they are highly effective in patients resistant to second-generation tyrosine kinase inhibitors.


Does the FDA approve Ponatinib?

Ponatinib was initially stopped from marketing due to its serious adverse effects. However, in 2020, the United States Food and Drug Administration (FDA) approved Ponatinib for treating patients with chronic phase of chronic myeloid leukemia who were intolerant or resistant to any two prior kinase inhibitors.


How Does Ponatinib Work?

Ponatinib is a third-generation tyrosine kinase inhibitor that inhibits the enzyme activity of BCR-ABL protein kinase. However, it is a multi-kinase inhibitor that prevents tumor cell proliferation, migration, and invasion.


How Long Is the Half-Life of Ponatinib?

In general, the half-life of Ponatinib is between 12 and 66 hours and, on average, 24 hours after oral administration of 45 mg of the drug. It is commonly metabolized in the liver and by esterases or amidases.


Why Is Ponatinib Not Available in the Market?

The effectiveness of Ponatinib was continuously monitored through trials, which revealed that the drug leads to severe adverse vascular effects. Hence, the FDA (Food and Drug Administration) stopped marketing Ponatinib in October 2013.


How to Administer Ponatinib?

Ponatinib is available in tablet form. It can be taken orally, once daily, with water, and with or without food. The recommended administration dosage is 45 mg, which continues until the patient shows significant progression or unacceptable toxicity.

Last reviewed at:
10 Oct 2022  -  11 min read




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