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Drug Interactions between dabrafenib and mobocertinib

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

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Interactions between your drugs

Major

dabrafenib mobocertinib

Applies to: dabrafenib and mobocertinib

GENERALLY AVOID: Coadministration with strong or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations and anti-cancer activity of mobocertinib, which is primarily metabolized by the isoenzyme. Based on drug interaction studies using model-informed approaches, coadministration of mobocertinib with multiple doses of rifampin (a strong CYP450 3A4 inducer) is predicted to decrease the steady-state combined molar AUC (systemic exposure) of mobocertinib and its active metabolites by 92%, while coadministration with multiple doses of efavirenz (a moderate CYP450 3A4 inducer) is predicted to decrease this value by 58%.

MANAGEMENT: Coadministration of mobocertinib with strong or moderate CYP450 3A4 inducers should be avoided.

References

  1. "Product Information. Exkivity (mobocertinib)." Takeda Pharmaceuticals America ORIG-1 (2021):
  2. "Product Information. Exkivity (mobocertinib)." Takeda UK Ltd (2022):
  3. "Product Information. Exkivity (mobocertinib)." Takeda Pharmaceuticals Australia Pty Ltd EXKIVITY PI V1.0 (CC (2022):

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Drug and food interactions

Major

mobocertinib food

Applies to: mobocertinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mobocertinib. The mechanism may involve inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice. Based on drug interaction studies using model-informed approaches, coadministration of mobocertinib with multiple doses of itraconazole or ketoconazole (strong CYP450 3A4 inhibitors) is predicted to increase the steady-state combined molar AUC (systemic exposure) of mobocertinib and its active metabolites by 374% to 419%, while coadministration with multiple doses of a moderate CYP450 3A4 inhibitor is predicted to increase this value by approximately 100% to 200%. 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. Elevated plasma concentrations of mobocertinib may increase the risk for adverse effects such as QT prolongation, heart failure or reduced ejection fraction, cardiomyopathy, heart block, diarrhea, rash, stomatitis, fatigue, and musculoskeletal pain.

MANAGEMENT: Patients should avoid consumption of grapefruit and grapefruit juice during treatment with mobocertinib.

References

  1. "Product Information. Exkivity (mobocertinib)." Takeda Pharmaceuticals America ORIG-1 (2021):
  2. "Product Information. Exkivity (mobocertinib)." Takeda UK Ltd (2022):

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Moderate

dabrafenib food

Applies to: dabrafenib

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.

References

  1. "Product Information. Tafinlar (dabrafenib)." GlaxoSmithKline (2013):

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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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