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Drug Interactions between darunavir and nirogacestat

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

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Interactions between your drugs

Major

darunavir nirogacestat

Applies to: darunavir and nirogacestat

GENERALLY AVOID: Coadministration with potent and moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentration and pharmacologic effects of nirogacestat, which is primarily metabolized by the isoenzyme. Drug interaction studies have shown that coadministration with the potent CYP450 3A4 inhibitor itraconazole increased the systemic exposure (AUC) and peak plasma concentration (Cmax) of a single 100 mg dose of nirogacestat by 8.2-fold and 2.5-fold, respectively. Administration of multiple doses of nirogacestat (150 mg twice daily) with the potent CYP450 3A4 inhibitors itraconazole, ketoconazole, and clarithromycin is predicted to increase the AUC of nirogacestat by 6.33-fold, 5.19-fold, and 3.46-fold, respectively. In addition, 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. 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: According to the manufacturer, concomitant use of nirogacestat with potent and moderate CYP450 3A4 inhibitors should be avoided.

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

Drug and food interactions

Major

nirogacestat food

Applies to: nirogacestat

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

darunavir food

Applies to: darunavir

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References (1)
  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech 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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