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Drug Interactions between lapatinib and tepotinib

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

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Interactions between your drugs

Moderate

lapatinib tepotinib

Applies to: lapatinib and tepotinib

MONITOR: Coadministration with tepotinib may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of P-glycoprotein (P-gp). The proposed mechanism is decreased clearance due to tepotinib-mediated inhibition of P-gp efflux transport protein. Coadministration with tepotinib increased the peak plasma concentration (Cmax) and systemic exposure (AUC0-INF) of dabigatran (a P-gp substrate) by 40% and 50%, respectively.

MANAGEMENT: Caution is advised when tepotinib is used concomitantly with drugs that are substrates of P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever tepotinib is added to or withdrawn from therapy. Patients should be monitored for the development of adverse effects. The prescribing information recommends avoiding concomitant use of tepotinib with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. When concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

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

Moderate

lapatinib food

Applies to: lapatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.

References (1)
  1. (2007) "Product Information. Tykerb (lapatinib)." 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

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.

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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