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Drug Interactions between binimetinib and ceritinib

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

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Interactions between your drugs

Moderate

ceritinib binimetinib

Applies to: ceritinib and binimetinib

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp), uridine diphosphate glucuronosyltransferase (UGT) 1A1 or 2B7, and/or breast cancer resistance protein (BCRP) may increase the plasma levels and risk of adverse effects of binimetinib. The proposed mechanism involves the reduced metabolic clearance of binimetinib through inhibition of P-gp, UGT 1A1, UGT 2B7, and/or BCRP. The clinical significance of this interaction is unknown as no clinically relevant drug interactions have been demonstrated with binimetinib.

MANAGEMENT: Until further information is available, caution is recommended if binimetinib must be used concomitantly with P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitors. Binimetinib should be monitored more closely whenever a P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitor is added to or withdrawn from therapy, and the binimetinib dosage adjusted as necessary.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2018) "Product Information. Mektovi (binimetinib)." Array BioPharma Inc.

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

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Multikinase inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

  • binimetinib
  • ceritinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.