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Drug Interactions between Ambien CR and nirogacestat

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

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Interactions between your drugs

Moderate

zolpidem nirogacestat

Applies to: Ambien CR (zolpidem) and nirogacestat

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of zolpidem, which is partially metabolized by the isoenzyme. When a single 5 mg dose of zolpidem was administered to 12 healthy study subjects following treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 2 days), zolpidem peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 35% and 67%, respectively. Increased sedation and other pharmacodynamic effects were noted.

MANAGEMENT: Caution is advised when zolpidem is used with CYP450 3A4 inhibitors. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them, and to notify their physician if they experience excessive somnolence or dizziness.

References

  1. "Product Information. Ambien (zolpidem)." sanofi-aventis PROD (2001):
  2. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  3. Luurila H, Kivisto KT, Neuvonen PJ "Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem." Eur J Clin Pharmacol 54 (1998): 163-6
  4. Greenblatt DJ, vonMoltke LL, Harmatz JS, Mertzanis P, Graf JA, Durol ALB, Counihan M, RothSchechter B, Shader RI "Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole." Clin Pharmacol Ther 64 (1998): 661-71
  5. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. "Differential impairment of triazolam and zolpidem clearance by ritonavir." J Acquir Immune Defic Syndr 24 (2000): 129-36
  6. Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT "Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects." Br J Clin Pharmacol 63 (2007): 116-20
  7. Farkas D, Volak L, Harmatz J, von Moltke L, Court M, Greenblatt D "Short-term clarithromycin administration impairs clearance and enhances pharmacodynamic effects of trazodone but not of zolpidem." Clin Pharmacol Ther 85 (2009): 644-50
View all 7 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

zolpidem food

Applies to: Ambien CR (zolpidem)

You should avoid the use of alcohol while being treated with zolpidem. Alcohol can increase the nervous system side effects of zolpidem such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. Taking zolpidem with food may delay the onset of sleep. For faster sleep onset, zolpidem should not be taken with or immediately after a meal. This will make it easier for your body to absorb the medication. Talk to your doctor or pharmacist if you have any questions or concerns.

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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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