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Drug Interactions between Daliresp and nirogacestat

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

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Interactions between your drugs

Moderate

roflumilast nirogacestat

Applies to: Daliresp (roflumilast) and nirogacestat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with nirogacestat may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 2C19. The proposed mechanism is increased clearance due to nirogacestat-mediated induction of CYP450 2C19. According to the manufacturer, concomitant use of a sensitive CYP450 2C19 substrate following multiple doses of nirogacestat is predicted to decrease the plasma concentration of the substrate. However, no pharmacokinetic data are available from drug interaction studies.

MANAGEMENT: The manufacturer advises that concomitant use of nirogacestat with drugs that are substrates of CYP450 2C19, particularly sensitive substrates or those with a narrow therapeutic range, where decreased concentrations may lead to a significant reduction in efficacy, should generally be avoided. If coadministration is considered necessary, patients should be monitored for diminished therapeutic effects. Clinical and laboratory monitoring should be considered whenever nirogacestat is added to or withdrawn from therapy with these drugs, and the dosage of the CYP450 2C19 substrate drug adjusted as necessary.

References

  1. "Product Information. Ogsiveo (nirogacestat)." SpringWorks Therapeutics, Inc. (2023):

Drug and food interactions

Major

nirogacestat food

Applies to: nirogacestat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit, grapefruit juice, Seville oranges, and starfruit may significantly increase the plasma concentrations and pharmacologic effects of nirogacestat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Coadministration of multiple doses of nirogacestat (150 mg twice daily) with the moderate CYP450 3A4 inhibitors erythromycin and fluconazole are predicted to increase the AUC of nirogacestat by 2.73-fold and 3.18-fold, respectively. The interaction has not been studied with grapefruit, Seville oranges, or starfruit. 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. Increased systemic exposure to nirogacestat may increase the risk of adverse effects including diarrhea, ovarian toxicity, hepatotoxicity, electrolyte abnormalities, and non-melanoma skin cancers.

MANAGEMENT: Patients treated with nirogacestat should avoid consumption of grapefruit, grapefruit juice, Seville oranges, starfruit, or any supplement containing grapefruit.

References

  1. "Product Information. Ogsiveo (nirogacestat)." SpringWorks Therapeutics, Inc. (2023):
Minor

roflumilast food

Applies to: Daliresp (roflumilast)

Information for this minor interaction is available on the professional version.

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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