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ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS › ANTINEOPLASTIC AGENTS › PROTEIN KINASE INHIBITORS › BCR-ABL tyrosine kinase inhibitors
ponatinib
L01EA05
Forms & Strengths
- Oral tablets: 15 mg
- Oral tablets: 30 mg
- Oral tablets: 45 mg
Adult Dosing
- Chronic myeloid leukemia (CML), chronic phase: 45 mg orally once daily
- CML accelerated or blast phase, or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL): 45 mg orally once daily
- Dose reduction or interruption recommended for arterial occlusive events, venous thromboembolism, heart failure, or hepatotoxicity
Pediatric Dosing
- Safety and efficacy in pediatric patients below the age of 18 years have not been established
Indications
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors
- Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to at least two prior kinase inhibitors
- Treatment of adult patients with T315I-mutated CML (chronic, accelerated, or blast phase) or T315I-mutated Ph+ ALL
Mechanism of Action
- Tyrosine kinase inhibitor that targets BCR::ABL1
- Inhibits native BCR::ABL1 as well as all single mutant forms, including the T315I gatekeeper mutation
- Also inhibits other kinases including VEGFR, PDGFR, FGFR, EPH receptors, and SRC family kinases
Contraindications
- Hypersensitivity to ponatinib or any of its components
Adverse Reactions
- Arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular events)
- Venous thromboembolism
- Heart failure and cardiac arrhythmias
- Hypertension
- Hepatotoxicity (elevated transaminases, bilirubin)
- Pancreatitis and elevated lipase/amylase
- Hemorrhage and myelosuppression (thrombocytopenia, neutropenia, anemia)
- Skin rash, dry skin, abdominal pain, fatigue, headache, constipation, pyrexia, nausea, arthralgia
Drug Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): increase ponatinib exposure; consider alternatives or reduce ponatinib dose if coadministration is unavoidable
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort): decrease ponatinib exposure; avoid coadministration
- Drugs that prolong the QT interval: increase risk of QT prolongation; monitor closely
Curated Content: Needs Vetting Before Put to Clinical Use