Drug General Information (ID: DDIWR76KVZ)
Drug Name			Ponatinib		Drug Info		Antithrombin III human		Drug Info
Drug Type		Small molecule				Protein/peptide
Therapeutic Class		Multikinase Inhibitors				Recombinant Antithrombin

Mechanism of Ponatinib-Antithrombin III human Interaction (Severity Level: Major)
Increased risk of bleeding Click to Show/Hide Mechanism Graph
Drug Name		Ponatinib				Antithrombin III human
Mechanism		Risk of bleeding Antiplatelet/anticoagulant effects				Risk of bleeding Anticoagulant
Key Mechanism Factor 1
		Factor Name		Bleeding
		Factor Description		Patients may be at risk for bleeding when the outcome of a disease or disease treatment confounds the standard mechanisms for maintaining hemostasis. Signs or symptoms of abnormal bleeding include: bleeding that takes a long time to stop (including nosebleeds, bleeding gums, bleeding from cuts and abrasions, and menstrual bleeding); severe unexplained bruising, or bruising that becomes larger; blood in the urine or stool, etc.
Mechanism Description		Increased risk of bleeding by the combination of Ponatinib and Antithrombin III human

Recommended Action
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.

References
1	Product Information. Brukinsa (zanubrutinib). BeiGene USA, Inc, San Mateo, CA.
2	Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.