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Drug Interactions between Tazverik and tepotinib

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

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Interactions between your drugs

Moderate

tazemetostat tepotinib

Applies to: Tazverik (tazemetostat) and tepotinib

MONITOR: Coadministration with CYP450 3A4 inducers and/or P-glycoprotein (P-gp) inducers may decrease the plasma concentrations 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 CYP450 3A4 inducers and/or P-gp inducers on tepotinib has not been studied clinically.

MANAGEMENT: The potential for diminished pharmacologic effects of tepotinib should be considered during coadministration with CYP450 3A4 inducers and/or P-gp inducers. Alternative treatments may be required if an interaction is suspected.

References

  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
View all 4 references

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Drug and food interactions

Major

tazemetostat food

Applies to: Tazverik (tazemetostat)

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during tazemetostat therapy may significantly increase the plasma concentrations of tazemetostat. The proposed mechanism is inhibition of the CYP450 3A4-mediated metabolism of tazemetostat by certain compounds in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). According to the product labeling, coadministration of tazemetostat (400 mg twice daily) with the moderate CYP450 3A4 inhibitor fluconazole increased the tazemetostat steady state exposure (AUC 0 to 8 hours) by 3.1-fold and peak plasma concentration by 2.3-fold. 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Clinically, this interaction may result in an increased risk of the frequency or severity of adverse reactions due to tazemetostat such as hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.

MANAGEMENT: The manufacturer advises that patients treated with tazemetostat should avoid consumption of grapefruit or grapefruit juice.

References

  1. (2020) "Product Information. Tazverik (tazemetostat)." Epizyme, Inc

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

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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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