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Drug Interactions between ivosidenib and ponatinib

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

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Interactions between your drugs

Moderate

PONATinib ivosidenib

Applies to: ponatinib and ivosidenib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of ponatinib, which is a substrate of the isoenzyme. The interaction has not been evaluated in vitro or in a clinical trial; however, a reduction in ponatinib exposure was observed in simulations using a mechanistic model.

MANAGEMENT: Coadministration of ponatinib in combination with potent CYP450 3A4 inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided unless the benefit outweighs the potential risk of ponatinib underexposure. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible. If concomitant use is required, close monitoring for signs of reduced therapeutic efficacy is advised. Other known inducers include aminoglutethimide, barbiturates, bexarotene, bosentan, dabrafenib, efavirenz, etravirine, nafcillin, nevirapine, somatrem, somatropin, and various other anticonvulsants, although the extent to which they interact with ponatinib is unknown.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2012) "Product Information. Iclusig (ponatinib)." Ariad Pharmaceuticals Inc

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Drug and food interactions

Major

ivosidenib food

Applies to: ivosidenib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivosidenib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. Pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, itraconazole, and the moderate inhibitor, fluconazole. When a single 250 mg dose of ivosidenib was administered with itraconazole 200 mg once daily for 18 days, ivosidenib systemic exposure (AUC) increased to 269% of control, with no change in peak plasma concentration (Cmax). Based on physiologically-based pharmacokinetic modeling, coadministration of a 500 mg dose of ivosidenib with fluconazole (dosed to steady-state) is predicted to increase ivosidenib single-dose AUC to 173% of control, while multiple-dosing of both is predicted to increase ivosidenib steady-state Cmax and AUC to 152% and 190% of control, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to ivosidenib may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

GENERALLY AVOID: Coadministration with a high-fat meal may increase the plasma concentrations of ivosidenib. According to the product labeling, administration of a single dose with a high-fat meal (approximately 900 to 1000 calories; 500 to 600 calories in fat, 250 calories in carbohydrate, 150 calories in protein) increased ivosidenib Cmax and AUC by 98% and 25%, respectively, in healthy study subjects.

MANAGEMENT: Ivosidenib may be administered with or without food, but should not be administered with a high-fat meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with ivosidenib.

References

  1. (2018) "Product Information. Tibsovo (ivosidenib)." Agios Pharmaceuticals, Inc.

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

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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.

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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