The median time to onset of the arterial occlusions was highly variable in phase 2 studies, though it was the shortest for cardiac vascular events (193 days) and longest for cerebrovascular events (526 days). Patients with and without cardiovascular risk factors developed arterial occlusions, which were more common among patients with concurrent risk factors such as hypertension, diabetes, hyperlipidemia, and history of prior cardiac events.
Ponatinib is also associated with heart failure in 9% of patients and, though it is not recommended in the PI, many patients who receive ponatinib are given baby aspirin.
Liver toxicity is also listed as a black box warning. In the some instances, hepatotoxicity led to fulminant hepatic failure and eventual death. Up to 11% of patients treated with ponatinib experienced grade 3 or 4 hepatotoxicity in the phase 2 clinical trial, though hepatotoxicity is now reported in close to 30% of patients. Most patients developed hepatotoxicity within the first 3 months of treatment, though onset ranged from less than 1 month to up to 47 months. Before starting ponatinib, baseline liver function tests should be obtained and then followed monthly.
Although ponatinib has an extensive side effect profile, these effects could be made more serious if the patient is taking concurrent medications. Ponatinib is a substrate for CYP3A, CYP2C8, and CYP2D6. Inhibitors of these enzymes may increase the plasma concentration of ponatinib, leading to more adverse events. Thorough medication reconciliation should be performed prior to starting ponatinib.
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As drug development for CML continues to advance, careful thought must be given to the characteristics of each medication before a treatment decision can be made. If a patient develops any adverse event while on ponatinib, clinicians should evaluate the clinical scenario and perform a risk-benefit analysis before deciding whether to continue treatment.
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- O’Dwyer ME, Mauro MJ, Blasdel C, et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood. 2004;103(2):451-5.
- ICLUSIG REMS (Risk Evaluation and Mitigation Strategy). http://www.iclusigrems.com/. Updated 2016. Accessed December, 2016.