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Drug Interactions between glycerol phenylbutyrate and Iclusig

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

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Interactions between your drugs

Moderate

PONATinib glycerol phenylbutyrate

Applies to: Iclusig (ponatinib) and glycerol phenylbutyrate

MONITOR: Coadministration of glycerol phenylbutyrate may lead to increased concentrations of CYP450 2D6 substrates. The proposed mechanism is inhibition of CYP450 2D6 by phenylbutyrate, the active moiety of glycerol phenylbutyrate, which has been shown to be an in vitro inhibitor of this isoenzyme. In in vitro studies, administration of phenylbutyrate at a concentration of 800 mcg/mL caused greater than 60% reversible inhibition of CYP450 2D6, 2C9, and 3A4/5. The clinical significance of these results has not been established; however, the manufacturer states that a potential interaction with CYP450 2D6 substrates cannot be ruled out.

MANAGEMENT: Caution is recommended if glycerol phenylbutyrate is administered with medicines that are substrates of CYP450 2D6, such as codeine, dextromethorphan, and some beta blockers (including metoprolol, carvedilol, labetalol, propranolol, and nebivolol). Dosage adjustments as well as clinical and laboratory monitoring may be appropriate.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Ravicti (glycerol phenylbutyrate)." Hyperion Therapeutics Inc (2013):

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Drug and food interactions

Moderate

PONATinib food

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

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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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