Drug Interactions between aspirin / pravastatin and ponatinib

MONITOR CLOSELY: Coadministration of ponatinib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Treatment with ponatinib is associated with severe, sometimes fatal hemorrhage including cerebral and gastrointestinal hemorrhage. In clinical trials, hemorrhagic events occurred in 24% of patients treated with ponatinib, and serious events occurred in 5% of patients. The incidence of serious bleeding events was higher in patients with accelerated phase or blast phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Most hemorrhagic events occurred in patients with grade 4 thrombocytopenia.

MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with ponatinib. Close clinical and laboratory observation for bleeding complications is recommended during therapy. The INR should be monitored more frequently during coadministration of warfarin. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

MONITOR: The risk of peripheral neuropathy may be increased during concurrent use of two or more agents that are associated with this adverse effect. Patient risk factors include diabetes and age older than 60 years. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

MANAGEMENT: Caution is advised during concomitant use of agents with neurotoxic effects. Patients should be monitored closely for symptoms of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Since the development of peripheral neuropathy may be dose-related for many drugs, the recommended dosages should generally not be exceeded. Consideration should be given to dosage reduction or immediate discontinuation of these medications in patients who develop peripheral neuropathy to limit further damage. If feasible, therapy should generally be reinstituted only after resolution of neuropathy symptoms or return of symptoms to baseline status. In some cases, permanent dosage reductions may be required.