Myelosuppression: Ponatinib is associated with severe (National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4) thrombocytopenia, neutropenia, and anaemia. Most of the patients with grade 3 or 4 platelet count decreased, anaemia or neutropenia, developed it within the first 3 months of treatment. The frequency of these events is greater in patients with accelerated phase CML (AP-CML) or blast phase CML (BP-CML)/Ph+ ALL than in chronic phase CML (CP-CML). A complete blood count should be performed every 2 weeks for the first 3 months and then monthly or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding ponatinib temporarily or reducing the dose.Arterial occlusion: Arterial occlusions, including fatal myocardial infarction, stroke, retinal arterial occlusions associated in some cases with permanent visual impairment or vision loss, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, renal artery stenosis (associated with worsening, labile ortreatment-resistant hypertension), and the need for urgent revascularization procedures have occurred in ponatinib-treated patients. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. Arterial occlusion adverse events were more frequent with increasing age and in patients with history of ischaemia, hypertension, diabetes, or hyperlipidaemia.Venous thromboembolism: Monitoring for evidence of thromboembolism should be performed. Ponatinib should be interrupted immediately in case of thromboembolism. A benefit -risk consideration should guide a decision to restart ponatinib therapy.Hypertension: During ponatinib treatment, blood pressure should be monitored and managed at each clinic visit and hypertension should be treated to normal. Ponatinib treatment should be temporarily interrupted if hypertension is not medically controlled.Congestive heart failure: Fatal and serious heart failure or left ventricular dysfunction occurred in ponatinib-treated patients, including events related to prior vascular occlusive events. Patients should be monitored for signs or symptoms consistent with heart failure and they should be treated as clinically indicated, including interruption of ponatinib. Discontinuation of ponatinib should be considered in patients who develop serious heart failure.Hepatotoxicity: Ponatinib may result in elevation in ALT, AST, bilirubin, and alkaline phosphatase. Most patients who had an event of hepatotoxicity had their first event during the first year of treatment. Hepatic failure (including fatal outcome) has been observed. Liver function tests should be performed prior to treatment initiation and monitored periodically, as clinically indicated.Haemorrhage: Severe haemorrhage, including fatalities, occurred in ponatinib treated patients. The incidence of severe bleeding events was higher in patients with AP-CML, BP-CML and Ph+ ALL. Ponatinib should be interrupted and patients evaluated for serious or severe haemorrhage.Hepatitis B reactivation: Reactivation of hepatitis B in patients who are chronic carriers of this virus has occurred after these patients received BCR-ABL tyrosine kinase inhibitors. Patients should be tested for HBV infection before initiating treatment with ponatinib. Carriers of HBV who require treatment with ponatinib should be closely monitored for signs and symptoms of active HBV infection throughout therapy and forseveral months following termination of therapy.
