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Drug Interactions between ceritinib and Enablex

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

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Interactions between your drugs

Major

darifenacin ceritinib

Applies to: Enablex (darifenacin) and ceritinib

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of darifenacin, which is partially metabolized by the isoenzyme. Darifenacin is also metabolized by CYP450 2D6, but 3A4 is the major pathway of metabolism in so-called poor metabolizers of 2D6 (approximately 7% of Caucasians and 2% of Asians and those of African descent). In a drug interaction study involving 10 extensive metabolizers and 1 poor metabolizer of 2D6, coadministration with the potent 3A4 inhibitor ketoconazole (400 mg) increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of darifenacin (extended-release 7.5 mg once a day) approximately 5-fold each compared to values previously reported for extensive metabolizers of 2D6. In the poor metabolizer, Cmax and AUC of darifenacin increased approximately 13-fold each compared to values previously reported for poor metabolizers. When a 15 mg daily dose of extended-release darifenacin was given with ketoconazole, mean darifenacin Cmax and AUC in 3 extensive metabolizers increased approximately 12-fold compared to historical values, while Cmax and AUC increased approximately 6-fold in the poor metabolizer compared to historical values.

MANAGEMENT: The dosage of darifenacin should not exceed 7.5 mg/day when used with potent CYP450 3A4 inhibitors. Some authorities recommend avoiding concomitant use of darifenacin during and for 2 weeks after treatment with itraconazole.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2005) "Product Information. Enablex (darifenacin)." Novartis Pharmaceuticals
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Niwa T, Shiraga T, Takagi A (2005) "Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, CYP3A4 activities in human liver microsomes." Biol Pharm Bull, 28, p. 1805-8
View all 4 references

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Drug and food interactions

Major

ceritinib food

Applies to: ceritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ceritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ceritinib 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. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ceritinib. The mechanism of interaction is unknown. Compared to the fast state, administration of a single 500 mg dose of ceritinib with a high-fat meal (approximately 1000 calories; 58 grams of fat) increased ceritinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 73%, respectively, and administration with a low-fat meal (approximately 330 calories; 9 grams of fat) increased ceritinib Cmax and AUC by 43% and 58%, respectively. A dose of 600 mg or higher taken with a meal is expected to produce systemic exposure exceeding that from a 750 mg dose taken in the fasted state, which may lead to increased adverse effects.

MANAGEMENT: Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).

References

  1. (2014) "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals

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Minor

darifenacin food

Applies to: Enablex (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.

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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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