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Drug Interactions between darifenacin and imatinib

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

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Interactions between your drugs

Moderate

imatinib darifenacin

Applies to: imatinib and darifenacin

MONITOR: Coadministration with inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations of darifenacin, which is a substrate of these isoenzymes. According to the product labeling, coadministration of darifenacin (30 mg once daily) with the mixed CYP450 inhibitor cimetidine resulted in a 42% increase in the mean darifenacin steady-state peak plasma concentration (Cmax) and a 34% increase in the systemic exposure (AUC) compared to administration of darifenacin alone. The potent CYP450 2D6 inhibitor paroxetine (20 mg) increased steady-state AUC of darifenacin (30 mg once daily) by 33%. Erythromycin, a CYP450 3A4 inhibitor, increased the mean steady-state Cmax and AUC of darifenacin (30 mg once daily) by 128% and 95%, respectively. Fluconazole, another 3A4 inhibitor, increased these values by 88% and 84%, respectively.

MANAGEMENT: Pharmacologic response to darifenacin should be monitored more closely whenever a CYP450 2D6 and/or 3A4 inhibitor is added to or withdrawn from therapy, and the darifenacin dosage adjusted if necessary. Patients should be advised to contact their physician if they experience undue adverse effects of darifenacin such as severe abdominal pain or constipation for 3 or more days.

References

  1. (2005) "Product Information. Enablex (darifenacin)." Novartis Pharmaceuticals
  2. (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc

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Drug and food interactions

Moderate

imatinib food

Applies to: imatinib

GENERALLY AVOID: Coadministration of imatinib with strong CYP450 3A4 inhibitors such as grapefruit juice, may significantly increase the plasma concentrations of imatinib, a known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of imatinib by certain compounds present in grapefruits. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. In a single-dose study, coadministration of imatinib with ketoconazole (a strong CYP450 3A4 inhibitor) increased imatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 26% and 40%, respectively.

MANAGEMENT: Patients treated with imatinib should preferably avoid the consumption of grapefruit or grapefruit juice. If coadministration is unavoidable, monitor for prolonged and/or increased pharmacologic effects of imatinib, including edema, hematologic toxicity and immunosuppression.

References

  1. (2022) "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."

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Minor

darifenacin food

Applies to: darifenacin

The consumption of grapefruit juice may be associated with increased plasma concentrations of darifenacin. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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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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