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Drug Interactions between mitotane and tepotinib

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

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Interactions between your drugs

Major

mitotane tepotinib

Applies to: mitotane and tepotinib

GENERALLY AVOID: Coadministration with strong CYP450 3A4 inducers and/or P-glycoprotein (P-gp) inducers may decrease the plasma concentrations and anti-tumor activity of tepotinib. The proposed mechanism involves induction of CYP450 3A4, which is one of the primary enzymes responsible for the metabolic clearance of tepotinib, and induction of the efflux transporter P-gp, of which tepotinib is also a substrate. However, the effect of strong CYP450 3A4 inducers and/or P-gp inducers on tepotinib has not been studied clinically.

MANAGEMENT: Coadministration of tepotinib with strong CYP450 3A4 inducers and/or P-gp inducers should be avoided.

References (4)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. (2015) "Canadian Product Information."
  3. (2021) "Product Information. Tepmetko (tepotinib)." EMD Serono Inc
  4. (2022) "Product Information. Tepmetko (tepotinib)." Merck Healthcare Pty Ltd, A001-0122

Drug and food interactions

Moderate

mitotane food

Applies to: mitotane

ADJUST DOSING INTERVAL: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

References (4)
  1. (2023) "Product Information. Lysodren (mitotane)." HRA Pharma America
  2. (2023) "Product Information. Lysodren (mitotane)." Medunik Canada
  3. (2023) "Product Information. Lysodren (mitotane)." HRA Pharma UK & Ireland Ltd
  4. Moolenaar AJ, van Slooten H, van Seters AP, Smeenk D (2023) Blood levels of o,p-DDD following administration in various vehicles after a single dose and during long-term treatment https://link.springer.com/article/10.1007/BF00258213
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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