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Drug Interactions between midostaurin and tepotinib

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

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Interactions between your drugs

Moderate

midostaurin tepotinib

Applies to: midostaurin and tepotinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of tepotinib, which may increase the incidence and severity of adverse reactions such as interstitial lung disease/pneumonitis, hepatotoxicity, edema, nausea, vomiting, diarrhea, constipation, and musculoskeletal pain. Tepotinib is a substrate of both CYP450 3A4 isoenzyme and P-gp efflux transporter. However, the effect of CYP450 3A4 or P-gp inhibitors on tepotinib has not been studied clinically.

MANAGEMENT: Caution is advised when tepotinib is used with inhibitors of CYP450 3A4 and/or P-gp. Patients should be monitored for increased adverse effects, and the tepotinib dosage adjusted as necessary.

References (2)
  1. (2021) "Product Information. Tepmetko (tepotinib)." EMD Serono Inc
  2. (2022) "Product Information. Tepmetko (tepotinib)." Merck Healthcare Pty Ltd, A001-0122

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
Moderate

tepotinib food

Applies to: tepotinib

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of tepotinib. When tepotinib was administered after a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150 calories from protein, 250 calories from carbohydrate, 500 to 600 calories from fat), tepotinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2-fold and 1.6-fold, respectively, compared to administration under fasted conditions.

MANAGEMENT: Tepotinib should be administered with food at approximately the same time each day.

References (1)
  1. (2021) "Product Information. Tepmetko (tepotinib)." EMD Serono Inc

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:

  • midostaurin
  • tepotinib

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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