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Drug Interactions between crizotinib and ponatinib

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

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Interactions between your drugs

Moderate

crizotinib PONATinib

Applies to: crizotinib and ponatinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ponatinib, which is a substrate of the isoenzyme. In 22 healthy volunteers, administration of a single 15 mg oral dose of ponatinib in combination with the potent CYP450 3A4 inhibitor ketoconazole (400 mg daily) increased ponatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 47% and 78%, respectively, compared to administration of ponatinib alone. No data are available for use with less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised if ponatinib is used in combination with moderate CYP450 3A4 inhibitors. Patients should be monitored for potentially increased side effects such as thromboembolism, ischemia, congestive heart failure, hypertension, hepatotoxicity, pancreatitis, myelosuppression, hemorrhage, and fluid retention.

References (1)
  1. (2012) "Product Information. Iclusig (ponatinib)." Ariad Pharmaceuticals Inc

Drug and food interactions

Major

crizotinib food

Applies to: crizotinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.

References (1)
  1. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group
Moderate

PONATinib food

Applies to: ponatinib

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of ponatinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided during treatment with ponatinib.

References (1)
  1. (2012) "Product Information. Iclusig (ponatinib)." Ariad Pharmaceuticals Inc

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Multikinase inhibitors

Therapeutic duplication

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:

  • crizotinib
  • 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.

See also

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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.

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