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Drug Interactions between boceprevir and ceritinib

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

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Interactions between your drugs

Major

boceprevir ceritinib

Applies to: boceprevir and ceritinib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ceritinib, which is a substrate of the isoenzyme. In 19 healthy subjects, administration of a single 450 mg dose of ceritinib with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 14 days) increased ceritinib peak plasma concentration (Cmax) by 22% and systemic exposure (AUC) by 2.9-fold. The steady-state AUC of ceritinib at reduced doses after coadministration with ketoconazole 200 mg twice daily for 14 days was predicted by simulations to be similar to the steady-state AUC of ceritinib administered alone. 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.

MANAGEMENT: Concomitant use of ceritinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of ceritinib during and for 2 weeks after treatment with itraconazole. If coadministration is required, the manufacturer recommends a reduction of the ceritinib dosage by approximately one-third, rounded to the nearest 150 mg dosage strength. Patients should have periodic ECGs and be monitored for arrhythmias when QT interval is prolonged. A QTc interval exceeding 500 msec on at least two separate ECGs will require suspension of ceritinib therapy and immediate action to correct any concomitant risk factors before resuming treatment with a 150 mg dosage reduction. 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. Following discontinuation of the potent CYP450 3A4 inhibitor, ceritinib therapy should be resumed at the dosage that was taken prior to initiating the CYP450 3A4 inhibitor.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

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

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Moderate

boceprevir food

Applies to: boceprevir

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.

References

  1. "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation (2011):

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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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