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Drug Interactions between ponatinib and vadadustat

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

PONATinib vadadustat

Applies to: ponatinib and vadadustat

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with vadadustat may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4, CYP450 2C8 and CYP450 2C9 isoenzymes as well as substrates of the organic anion transporter 3 (OAT3). Vadadustat is an inhibitor of CYP450 3A4 and CYP450 2C8 in vitro and an inhibitor of CYP450 2C9 and OAT3 in vivo. A drug interaction study evaluating the effect of vadadustat (600 mg) on the pharmacokinetics of celecoxib, a CYP450 2C9 substrate, showed an increase in peak plasma concentration (Cmax) and systemic exposure (AUC) by 60% and 11%, respectively. In another drug interaction study evaluating the effect of repeat doses of vadadustat (600 mg once daily) on the pharmacokinetics of furosemide, an OAT1/OAT3 substrate, a 2-fold increase in furosemide systemic exposure (AUC) was observed. However, clinical data are not available for vadadustat with CYP450 3A4 or CYP450 2C8 substrates.

MONITOR: Coadministration of vadadustat with drugs that are known to increase the risk of gastrointestinal erosion may increase the risk of gastric or esophageal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, were reported during vadadustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat is coadministered with drugs that are substrates of CYP450 3A4, CYP450 2C8, CYP450 2C9 and/or OAT3 and that also carry a known risk of gastrointestinal erosion including certain NSAIDs (e.g., naproxen, ibuprofen, diclofenac), corticosteroids (e.g., methylprednisolone, prednisolone, prednisone), and certain chemotherapeutic agents (e.g., kinase inhibitors, paclitaxel, docetaxel). Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools. Monitoring for other signs and symptoms of increased exposure to the affected substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 3A4, CYP450 2C8, CYP450 2C9 and/or OAT3 inhibitor.

Drug and food interactions

Moderate

PONATinib food

Applies to: ponatinib

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.

Moderate

vadadustat food

Applies to: vadadustat

Consumer information for this interaction is not currently available.

MONITOR: Smoking and alcohol consumption during therapy with vadadustat may increase the risk of gastrointestinal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, have been reported during vadadustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat is prescribed to current tobacco smokers or alcohol drinkers. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.