Table 1 Dose reduction recommendations (as of 2013)

Dose reduction recommendations

In October 2013, the following specific recommendations were formulated after discussions with the US FDA on evolving observations of arterial occlusive events in patients treated with ponatinib:

All chronic phase chronic myeloid leukemia (CP-CML) patients on study who already had achieved major cytogenetic response (MCyR) should have had their dose reduced to 15 mg daily, unless, in the judgment of the investigator, the benefit/risk analysis, taking into account the patient's disease characteristics, BCR::ABL mutation status, and the patient's cardiovascular risk justified treatment with a higher dose

All CP-CML patients on study who had not yet achieved MCyR should have had their dose reduced to 30 mg daily, unless, in the judgment of the investigator, the benefit/risk analysis, taking into account the patient's disease characteristics, BCR::ABL mutation status, and the patient's cardiovascular risk justified treatment with a higher dose

All acute phase chronic myeloid leukemia (AP-CML), blast phase chronic myeloid leukemia (BP-CML), and Ph+ acute lymphoblastic leukemia (ALL) patients on study should have had their dose reduced to 30 mg daily, unless, in the judgment of the investigator, the benefit/risk analysis, taking into account the patient's disease characteristics, BCR::ABL mutation status, and the patient's cardiovascular risk justified treatment with a higher dose

All patients who lost response at a lower dose may have their dose escalated (up to a maximum of 45 mg daily) as long as the dose was not lowered as a result of an adverse event (AE)