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Ponatinib

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Information about Ponatinib

Ponatinib is a tyrosine kinase receptor inhibitor that is used in the therapy of refractory chronic myelogenous leukemia (CML) positive for the Philadelphia chromosome.

Ponatinib
Ponatinib

Liver safety of Ponatinib

Ponatinib is commonly associated with transient elevations in serum aminotransferase levels during treatment, but with only rare instances of clinically apparent acute liver injury.

Mechanism of action of Ponatinib

Ponatinib (poe na’ ti nib) is a broad spectrum inhibitor of the unique BCR-ABL tyrosine kinase receptor, which is the product of a fusion gene resulting from the translocation between chromosomes 9 and 22 that underlies the Philadelphia chromosome of chronic myelogenous leukemia (CML). The abnormal tyrosine kinase receptor is constitutively expressed and causes abnormal cell growth and proliferation. Inhibition of the enzyme can lead to dramatic reversal of progression of leukemia and is highly effective, although limited by the development of tumor resistance caused by mutations in the kinase. Ponatinib is actually a multi-kinase inhibitor and also has activity against scr, c-Kit and ephrin receptors, among others.

FDA approval information for Ponatinib

Ponatinib received approval for use in the United States in 2012 and was one of 5 such specific inhibitors of BCR-ABL approved for clinical use, the others being imatinib [2001], dasatinib [2006], nilotinib [2007], and bosutinib [2012]. Ponatinib was subsequently withdrawn after identification of severe side effects of vascular thromboses, but then reapproved with a narrowing of indications and boxed warnings.

Dosage and administration for Ponatinib

Ponatinib is available in tablets of 15 and 45 mg under the brand name Inclusig. Current indications are as second line treatment of Philadelphia chromosome-positive CML in the chronic, accelerated or blast phase with the specific T315I mutation or after failure of all other BCR-ABL tyrosine kinase receptor inhibitors. The typical dose is 45 mg once daily to continue until the disease progresses or intolerable side effects arise.

Side effects of Ponatinib

Common side effects include hypertension, rash, abdominal pain, nausea, constipation, arthralgias, headache, fatigue, fever and bone marrow suppression. Less common, but severe side effects include heart failure (5%), pancreatitis (6%), neuropathy (13%), ocular toxicity (3%) and arterial and venous thromboses (27%) including myocardial infarction, stroke and peripheral vascular disease.

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Reviews for Ponatinib

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