Ponatinib

Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL with IC 50 concentrations of 0.4 nM and 2.0 nM, respectively.

• ICLUSIG ® is indicated for the treatment of adult patients with: Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Newly diagnosed Ph+ ALL in combination with chemotherapy. This indication is approved under accelerated approval based on minimal residual disease (MRD)-negative complete remission (CR) at the end of induction [see Clinical Studies (14) ] .ICD-10: C95.90

• None. None.contraindicated

Recommended Dosage in Newly Diagnosed Ph+ ALL : Starting dose is 30 mg orally once daily in combination with chemotherapy, with a reduction to 15 mg once daily upon achievement of MRD-negative (≤0.01% BCR::ABL1/ABL1) CR at the end of induction. ( 2.1 ) Recommended Dosage in Monotherapy for Ph+ ALL for Whom No Other Kinase Inhibitors are Indicated or T315I-positive Ph+ ALL : Starting dose is 45 mg orally once daily. ( 2.1 ) Recommended Dosage in CP-CML : Starting dose is 45 mg orally once daily with a reduction to 15 mg once daily upon achievement of ≤1% BCR::ABL1 IS . ( 2.1 ) Recommended Dosage in AP-CML and BP-CML : Starting dose is 45 mg orally once daily. ( 2.1 ) Hepatic Impairment : See the Full Prescribing Information for dosage modifications for hepatic impairment. ( 2.4 ) ICLUSIG may be taken with or without food. ( 2.1 ) 2.1 Recommended Dosage Newly Diagnosed Ph+ ALL The recommended starting dosage of ICLUSIG in combination with chemotherapy is 30 mg orally once daily with a reduction to 15 mg orally once daily upon achievement of MRD-negative (≤0.01% BCR::ABL1/ABL1) CR at the end of induction. Continue ICLUSIG in combination with chemotherapy for up to 20 cycles until loss of response or unacceptable toxicity [see Clinical Studies (14) ] . For a description of dosing of agents administered in combination with ICLUSIG, [see Clinical Studies (14) ] . Monotherapy for Ph+ ALL for Whom No Other Kinase Inhibitors Are Indicated or T315I-positive Ph+ ALL The optimal dose of ICLUSIG has not been identified.

Hypertension : Monitor blood pressure and manage hypertension as clinically indicated. Interrupt, dose reduce or stop ICLUSIG if hypertension is not medically controlled. ( 2.2 , 5.5 ) Pancreatitis : Monitor serum lipase. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on severity. Evaluate for pancreatitis when lipase elevation is accompanied by abdominal symptoms. ( 2.2 , 5.6 ) Neuropathy : Monitor for symptoms of peripheral and cranial neuropathy. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity. ( 2.2 , 5.8 ) Ocular Toxicity : Conduct comprehensive eye exams at baseline and periodically during treatment. ( 5.9 ) Hemorrhage : Monitor for hemorrhage and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity. ( 2.2 , 5.10 ) Fluid Retention : Monitor for fluid retention and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity. ( 2.2 , 5.11 ) Cardiac Arrhythmias : Monitor for signs or symptoms of arrhythmias and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity. ( 5.12 ) Myelosuppression : Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated.

The following clinically significant adverse reactions are described elsewhere in the labeling: Arterial Occlusive Events [see Warnings and Precautions (5.1) ] Venous Thromboembolic Events [see Warnings and Precautions (5.2) ] Heart Failure [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Hypertension [see Warnings and Precautions (5.5) ] Pancreatitis [see Warnings and Precautions (5.6) ] Neuropathy [see Warnings and Precautions (5.8) ] Ocular Toxicity [see Warnings and Precautions (5.9) ] Hemorrhage [see Warnings and Precautions (5.10) ] Fluid Retention [see Warnings and Precautions (5.11) ] Cardiac Arrhythmias [see Warnings and Precautions (5.12) ] Myelosuppression [see Warnings and Precautions (5.13) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.14) ] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.15) ] Impaired Wound Healing and Gastrointestinal Perforation [see Warnings and Precautions (5.16) ] Most common adverse reactions (occurring in >20% of patients) are: ICLUSIG as a single agent: rash and related conditions, arthralgia, abdominal pain, fatigue, headache, constipation, hypertension, dry skin, hepatotoxicity, fluid retention and edema, pyrexia, pancreatitis/lipase elevation, nausea, hemorrhage, anemia, AOEs, and cardiac arrhythmias. The most common Grade 3 or 4 laboratory abnormalities (>20%) are platelet count decreased, neutrophil cell count decreased, and white blood cell decreased.

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology (12.1) ] , ICLUSIG can cause fetal harm when administered to a pregnant woman. There are no available data on ICLUSIG use in pregnant women. In animal reproduction studies, oral administration of ponatinib to pregnant rats during organogenesis caused adverse developmental effects at doses lower than human exposures at the maximum recommended human dose of 45 mg/day (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Ponatinib was studied for effects on embryo-fetal development in pregnant rats given oral doses of 0.3 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day during organogenesis (25 rats per group). At the maternally toxic dose of 3 mg/kg/day (equivalent to the AUC in patients receiving the maximum recommended dose of 45 mg/day), ponatinib caused embryo-fetal toxicity as shown by increased resorptions, reduced body weight, external alterations, multiple soft tissue and skeletal alterations, and reduced ossification.

Metabolism

Ponatinib administered to patients with cancer exhibited approximately dose proportional increases in both steady-state C max and AUC over the dose range of 2 mg to 60 mg (0.04 to 1.33 times the approved maximum recommended starting dose). The mean (CV%) C max and AUC( 0-24 ) of ICLUSIG 45 mg orally once daily at presumed steady-state in patients with advanced hematologic malignancies were 73 ng/mL (74%) and 1253 ng∙hr/mL (73%), respectively.

Overdoses with ICLUSIG were reported in clinical trials. One patient was estimated to have been administered 540 mg via nasogastric tube. Two hours after the overdosage, the patient had an uncorrected QT interval of 520 ms. Subsequent ECGs showed normal sinus rhythm with uncorrected QT intervals of 480 ms and 400 ms. The patient died 9 days after the overdosage from pneumonia and sepsis. Another patient self-administered 165 mg on Cycle 1 Day 2. The patient experienced fatigue and non-cardiac chest pain on Day 3. Multiple doses of 90 mg per day for 12 days in a patient resulted in pneumonia, systemic inflammatory response, atrial fibrillation, and a moderate pericardial effusion. In the event of an overdosage, stop ICLUSIG, observe the patient and provide supportive treatment as appropriate.

• Dec 14, 2012NDANDA203469Takeda Pharms Usa

1. 1Death73414%
2. 2Off Label Use3436.7%
3. 3Rash2685.2%
4. 4Headache2655.2%
5. 5Fatigue2565.0%
6. 6Pyrexia2545.0%
7. 7Neoplasm Progression1973.8%
8. 8Constipation1923.7%
9. 9Hypertension1923.7%
10. 10Nausea1913.7%
11. 11Drug Ineffective1903.7%
12. 12Platelet Count Decreased1663.2%
13. 13Arthralgia1653.2%
14. 14Abdominal Pain1593.1%
15. 15Dry Skin1482.9%

The 10 most recently updated of 89 ClinicalTrials.gov registrations naming Ponatinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Decitabine, Venetoclax, and Ponatinib for the Treatment of Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase or Accelerated Phase Chronic Myelogenous Leukemia
  Completed · Phase 2 · Interventional · 20 enrolled · M.D. Anderson Cancer Center
  NCT04188405updated 2026-06-05
• A Study of LP-118 In Combination With Ponatinib, Dexamethasone And Blinatumomab For Adults With Newly-Diagnosed, BCR::ABL1-Positive Acute Lymphoblastic Leukemia (ALL)
  Not yet recruiting · Phase 1 · Interventional · 26 enrolled · Wake Forest University Health Sciences
  NCT07614022updated 2026-06-05
• Study of Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia With Inotuzumab Ozogamicin (InO)
  Recruiting · Phase 2 · Interventional · 25 enrolled · University of Chicago
  NCT04747912updated 2026-06-05
• Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
  Recruiting · Phase 2 · Interventional · 84 enrolled · National Cancer Institute (NCI)
  NCT03739814updated 2026-06-03
• Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemia
  Recruiting · Phase 2 · Interventional · 90 enrolled · M.D. Anderson Cancer Center
  NCT03263572updated 2026-05-20
• Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment of Ph+ CML Resistant/Intolerant to ≥3 Prior CML Therapies
  Terminated · Phase 1 · Phase 2 · Interventional · 124 enrolled · Sun Pharma Advanced Research Company Limited
  NCT02629692updated 2026-05-13
• Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
  Active not recruiting · Phase 3 · Interventional · 348 enrolled · National Cancer Institute (NCI)
  NCT04530565updated 2026-05-13
• Subcutaneous Blinatumomab Plus Ponatinib for BCR-ABL+ B-ALL
  Not yet recruiting · Phase 2 · Interventional · 80 enrolled · University of Alberta
  NCT07301424updated 2026-05-06
• A Phase II Study of the Combination of Ponatinib With Mini-hyper CVD Chemotherapy and Venetoclax in Patients With Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia
  Terminated · Phase 2 · Interventional · 4 enrolled · M.D. Anderson Cancer Center
  NCT05268003updated 2026-04-27
• Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.
  Recruiting · Phase 2 · Interventional · 20 enrolled · Novartis Pharmaceuticals
  NCT06514534updated 2026-04-21

Frequently asked questions

How does Ponatinib work?

Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL with IC 50 concentrations of 0.4 nM and 2.0 nM, respectively.

What is Ponatinib used for?

According to FDA labeling, Ponatinib carries indications including: ICLUSIG ® is indicated for the treatment of adult patients with: Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Newly diagnosed Ph+ ALL in combination with chemotherapy. This indication is approved under accelerated approval based on minimal residual disease (MRD)-negative complete remission (CR) at the end of induction [see Clinical Studies (14) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ponatinib?

Ponatinib is classified as BCR-ABL tyrosine kinase inhibitors, Kinase Inhibitor, Protein Kinase Inhibitors, Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration, Cellular Synthetic Activity Alteration.

What are the brand names for Ponatinib?

Ponatinib is marketed under brand names including Iclusig.

What are the contraindications for Ponatinib?

Ponatinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.