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Drug Interactions between ponatinib and Tasigna

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

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Interactions between your drugs

Moderate

nilotinib PONATinib

Applies to: Tasigna (nilotinib) and ponatinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the plasma concentrations of nilotinib, which is a substrate of both the isoenzyme and the efflux transporter. In healthy subjects receiving the potent inhibitor ketoconazole (400 mg once daily for 6 days), nilotinib systemic exposure (AUC) was increased approximately 3-fold. Because nilotinib 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. Data are not available for nilotinib in combination with other CYP450 3A4 or P-glycoprotein inhibitors. Theoretically, a reverse interaction may also occur, since many CYP450 3A4 and P-glycoprotein inhibitors are also substrates, and nilotinib is an inhibitor of both.

MANAGEMENT: Caution is advised if nilotinib is prescribed in combination with CYP450 3A4 and/or P-glycoprotein inhibitors. Pharmacologic response to nilotinib should be monitored more closely whenever a CYP450 3A4 or P-glycoprotein inhibitor is added to or withdrawn from therapy, and the nilotinib dosage adjusted as necessary. Patients should have frequent ECGs and be monitored for arrhythmias when QT interval is prolonged. A QTc interval exceeding 480 msec will require suspension of nilotinib therapy and immediate action to correct any concomitant risk factors before resuming treatment. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Patients should also be monitored for altered efficacy and safety of the concomitant administered drug.

References (1)
  1. (2007) "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals

Drug and food interactions

Major

nilotinib food

Applies to: Tasigna (nilotinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of nilotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because nilotinib 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.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of nilotinib. The mechanism of interaction is unknown. Compared to the fast state, nilotinib systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high-fat meal. Because nilotinib 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.

MANAGEMENT: Patients treated with nilotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. In addition, no food should be consumed for at least 2 hours before and 1 hour after a nilotinib dose.

References (1)
  1. (2007) "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals
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

Bcr-abl tyrosine kinase inhibitors

Therapeutic duplication

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

  • ponatinib
  • Tasigna (nilotinib)

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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