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Drug Interactions between ceritinib and talazoparib

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

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Interactions between your drugs

Moderate

ceritinib talazoparib

Applies to: ceritinib and talazoparib

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of talazoparib, which has been shown in vitro to be a substrate of both efflux membrane transporters. In clinical studies, administration of talazoparib with the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil resulted in an approximate 45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction. In contrast, coadministration with the P-gp inhibitors azithromycin, atorvastatin, diltiazem, felodipine, fluvoxamine, and quercetin increased talazoparib exposure by just 8%. The effect of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied.

MANAGEMENT: No initial dosage adjustment is recommended by the manufacturer when talazoparib is coadministered with inhibitors of BCRP and/or P-gp other than amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil. However, patients should be closely monitored for adverse effects such as myelosuppression and myelodysplastic syndrome/acute myeloid leukemia, and dosage adjustments made or treatment withheld as needed in accordance with the product labeling.

References (1)
  1. (2018) "Product Information. Talzenna (talazoparib)." Pfizer U.S. Pharmaceuticals Group

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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