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Drug Interactions between binimetinib and midostaurin

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

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Interactions between your drugs

Moderate

midostaurin binimetinib

Applies to: midostaurin 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 Binimetinib should be monitored more closely whenever a P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitor is added to or withdrawn from therapy, and the binimetinib dosage adjusted as necessary.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

midostaurin food

Applies to: midostaurin

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of midostaurin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Ketoconazole, a potent CYP450 3A4 inhibitor, has been shown to increase midostaurin systemic exposure (AUC) by greater than 10-fold in healthy volunteers. Increased exposure to midostaurin may increase the risk of adverse effects such as nausea, vomiting, diarrhea, edema, hyperglycemia, hyperuricemia, QT prolongation, neutropenia, lymphopenia, thrombocytopenia, and anemia.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of midostaurin. Relative to fasting conditions, midostaurin systemic exposure (AUC) increased by approximately 1.2-fold when administered with a standard meal (457 calories; 50 g fat, 21 g proteins, 18 g carbohydrates) and 1.6-fold when administered with a high-fat meal (1007 calories; 66 g fat, 32 g proteins, 64 g carbohydrates), while midostaurin peak plasma concentration (Cmax ) decreased by 20% and 27%, respectively.

MANAGEMENT: The manufacturer recommends taking midostaurin with food. Midostaurin was administered with food in clinical trials. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with midostaurin.

References (1)
  1. (2017) "Product Information. Rydapt (midostaurin)." 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
  • midostaurin

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.

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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