Drug Interaction Report

Using PONATinib together with cabozantinib may increase the risk of bleeding. In clinical studies, treatment with PONATinib alone has been associated with severe and sometimes fatal hemorrhage. Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. You should seek immediate medical attention if you experience any unusual bleeding or bruising, or have other signs and symptoms of bleeding such as dizziness; lightheadedness; red or black, tarry stools; coughing up or vomiting fresh or dried blood that looks like coffee grounds; severe headache; and weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Cabozantinib should be taken on an empty stomach, one hour before or two hours after a meal. Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with cabozantinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of cabozantinib. You may be more likely to experience side effects such as nausea; vomiting; diarrhea; loss of appetite; weight loss; mouth sores; abdominal pain; skin rash (primarily on the palms of the hands and soles of the feet); delayed wound healing; high blood pressure; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of bleeding problems and infections. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with PONATinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of PONATinib. You may be more likely to experience side effects such as nausea; vomiting; abdominal pain; constipation; skin rash; mouth sores; high blood pressure; blood clots; fluid retention; heart failure; liver damage; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of anemia, bleeding problems and infections. You should contact your doctor immediately if you develop sudden dizziness, fainting, chest pain, palpitation, shortness of breath, weakness on one side of the body, speech impairment, leg pain or swelling, or any signs of infection, as these may be symptoms of potentially serious side effects associated with PONATinib. You should also seek prompt medical attention if you have signs and symptoms of liver damage such as fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, light colored stools, and yellowing of the skin or eyes. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

The recommended maximum number of medicines in the 'VEGF/VEGFR inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'VEGF/VEGFR inhibitors' category:

• Cabometyx (cabozantinib)
• ponatinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• Cabometyx (cabozantinib)
• ponatinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.