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Drug Interactions between ceritinib and echinacea

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

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Interactions between your drugs

Moderate

echinacea ceritinib

Applies to: echinacea and ceritinib

MONITOR: Coadministration with echinacea may alter the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 3A4. Echinacea appears to inhibit intestinal CYP450 3A4, which would lead to an increase in oral midazolam (a sensitive 3A4 substrate) bioavailability; however, plasma levels of midazolam following oral administration do not appear to be affected by echinacea. In contrast, it appears that echinacea may also induce hepatic CYP450 3A4; thereby increasing the hepatic clearance of drugs that are substrates of CYP450 3A4. According to reports, echinacea may increase the hepatic clearance of intravenous (IV) midazolam by 34% and decrease the area under the concentration-time curve (AUC) and half-life of IV midazolam by 20% and 42%, respectively.

MANAGEMENT: In general, patients should be advised to consult their healthcare provider before using any herbal or alternative medicines. If echinacea is prescribed with a drug that is a CYP450 3A4 substrate, the possibility of an altered (increased or decreased) therapeutic response should be considered. Patients should be monitored more closely following the addition or withdrawal of echinacea and the dosage of the CYP450 3A4 substrate adjusted as necessary.

References (2)
  1. Gorski JC, Huang SM, Pinto A, et al. (2004) "The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo." Clin Pharmacol Ther, 75, p. 89-100
  2. Cerner Multum, Inc. "Australian Product Information."

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

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

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