Ponatinib requires particularly careful safety assessment because serious vascular, cardiovascular and hepatic events have occurred during treatment.
Boxed warning
The current U.S. ICLUSIG label contains a boxed warning covering:
- Arterial occlusive events
- Venous thromboembolic events
- Heart failure
- Hepatotoxicity
Arterial events have included myocardial infarction, stroke and severe peripheral vascular disease. Events have occurred in patients with and without traditional cardiovascular risk factors.
Cardiovascular and vascular safety
Healthcare professionals should assess cardiovascular and vascular health before and during treatment. Blood pressure and other cardiovascular risk factors should be appropriately managed.
The EMA has also emphasized the risk of arterial and venous occlusion with Iclusig and the importance of identifying and managing contributing risk factors.
Hepatotoxicity
Liver-function testing is required because severe hepatotoxicity, liver failure and fatal cases have occurred.
Hypertension
Blood pressure should be monitored. Uncontrolled hypertension may require treatment interruption, dose reduction or discontinuation.
Pancreatitis
Serum lipase monitoring is recommended. Abdominal symptoms associated with lipase elevation warrant evaluation for pancreatitis.
Neurologic and ocular effects
Ponatinib can cause neuropathy, ocular toxicity and reversible posterior leukoencephalopathy syndrome.
Bleeding and fluid retention
Hemorrhage and fluid retention can occur and should be assessed clinically.
Surgery
The label includes precautions concerning impaired wound healing and gastrointestinal perforation.
Pregnancy and breastfeeding
Ponatinib can cause fetal harm. The U.S. label advises against breastfeeding during treatment.
Drug interactions
Strong CYP3A inhibitors may require ponatinib dose modification, while strong CYP3A inducers should be avoided.