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Drug Interactions between nirogacestat and Yaz

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

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Interactions between your drugs

Moderate

drospirenone nirogacestat

Applies to: Yaz (drospirenone / ethinyl estradiol) and nirogacestat

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of drospirenone, which is partially metabolized by the isoenzyme. In a drug interaction study conducted in 20 premenopausal females, administration of a combined oral contraceptive containing drospirenone 3 mg and ethinyl estradiol 0.02 mg with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) for 10 days increased drospirenone peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.97- and 2.68-fold, respectively, compared to administration of the contraceptive alone. When a single dose of the contraceptive was coadministered with atazanavir/cobicistat (300 mg/150 mg once daily) in 14 healthy study subjects, drospirenone Cmax was not altered but AUC increased by 2.30-fold. Administration of the contraceptive with another potent CYP450 3A4 inhibitor, boceprevir (800 mg three times daily for 7 days), increased Cmax and AUC of drospirenone by 57% and 99%, respectively. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors. High exposure to drospirenone, a synthetic progestin and spironolactone analog, may potentiate the risk of hyperkalemia. When given at doses typically used for contraception, drospirenone has anti-mineralocorticoid activity comparable to a 25 mg dose of spironolactone.

MANAGEMENT: Caution and close clinical monitoring are recommended when drospirenone is prescribed with CYP450 3A4 inhibitors, particularly in patients requiring long-term concomitant use and those with other risk factors for hyperkalemia (e.g., renal insufficiency; coadministration with medications that can increase potassium such as aldosterone antagonists, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, and heparin). Consider checking serum potassium levels during the first treatment cycle and periodically thereafter as indicated.

References

  1. "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation (2011):
  2. "Product Information. Slynd (drospirenone)." Exeltis USA, Inc. (2022):
  3. "Product Information. Angeliq (drospirenone-estradiol)." Bayer Pharmaceutical Inc (2017):
  4. "Product Information. Slinda (drospirenone)." Besins Healthcare Australia Pty Ltd 03 - 04-2021 (2021):
  5. "Product Information. Angeliq 1/2 (drospirenone-estradiol)." Bayer Australia Limited (2021):
  6. "Product Information. Slynd (drospirenone)." Duchesnay Inc (2021):
  7. "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb (2022):
  8. "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb Australia Pty Ltd (2023):
  9. "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb Pharmaceuticals Ltd (2021):
View all 9 references

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):
Moderate

drospirenone food

Applies to: Yaz (drospirenone / ethinyl estradiol)

Grapefruit juice may increase the blood levels of certain medications such as drospirenone. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with drospirenone. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.

Switch to professional interaction data

Minor

ethinyl estradiol food

Applies to: Yaz (drospirenone / ethinyl estradiol)

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

Minor

ethinyl estradiol food

Applies to: Yaz (drospirenone / ethinyl estradiol)

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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