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Drug Interactions between cilostazol and nirogacestat

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

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Interactions between your drugs

Moderate

cilostazol nirogacestat

Applies to: cilostazol and nirogacestat

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or 2C19 may increase the plasma concentrations of cilostazol and or its pharmacologically active metabolites, which are substrates of these isoenzymes. The possibility of prolonged and/or increased pharmacologic effects of cilostazol should be considered. In pharmacokinetic studies, pretreatment with a 400 mg priming dose of ketoconazole (a potent CYP450 3A4 inhibitor) one day prior to coadministration of single doses of ketoconazole 400 mg and cilostazol 100 mg resulted in a 94% increase in cilostazol peak plasma concentration (Cmax) and a 117% increase in cilostazol systemic exposure (AUC). Coadministration of the less potent inhibitor erythromycin (500 mg every 8 hours) with a single 100 mg dose of cilostazol resulted in a 47% and 73% increase in cilostazol Cmax and AUC, respectively, while AUC of 4-trans-hydroxycilostazol (an active metabolite with 1/5 the pharmacologic activity) increased by 141% as a result of the inhibition of cilostazol metabolism via CYP450 3A4. Coadministration with 180 mg of diltiazem, a moderate CYP450 3A4 inhibitor, decreased cilostazol clearance by 30% and increased its Cmax by 30% and AUC by 40%. In contrast, cilostazol metabolism was not significantly affected when coadministered with omeprazole, a potent CYP450 2C19 inhibitor, but the systemic exposure to 3,4-dehydrocilostazol (the most active metabolite of cilostazol) was increased by 69%.

MANAGEMENT: Close clinical and laboratory monitoring is advised whenever a CYP450 3A4 and/or 2C19 inhibitor is added to or withdrawn from cilostazol therapy, and the dosage adjusted as necessary. Patients should be advised to contact their physician if they experience adverse effects of cilostazol such as dizziness, nausea, diarrhea, bleeding, or irregular heartbeat.

References

  1. McLellan RA, Drobitch RK, Monshouwer M, Renton KW "Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human." Drug Metab Dispos 24 (1996): 1134-8
  2. "Product Information. Pletal (cilostazol)." Otsuka American Pharmaceuticals Inc PROD (2001):
  3. Suri A, Bramer SL "Effect of omeprazole on the metabolism of cilostazol." Clin Pharmacokinet 37 (1999): 53-9
  4. Suri A, Forbes WP, Bramer SL "Effects of CYP3A inhibition on the metabolism of cilostazol." Clin Pharmacokinet 37 (1999): 61-8
  5. Herrlin K, Segerdahl M, Gustafsson LL, Kalso E "Methadone, ciprofloxacin, and adverse drug reactions." Lancet 356 (2000): 2069-70
  6. Hedaya MA, El-Afify DR, El-Maghraby GM "The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers." Biopharm Drug Dispos 27 (2006): 103-10
  7. Sawant RD "Rhabdomyolysis due to an uncommon interaction of ciprofloxacin with simvastatin." Can J Clin Pharmacol 16 (2009): e78-9
  8. Shahzadi A, Javed I, Aslam B, et al. "Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers." Pak J Pharm Sci 24 (2011): 63-8
  9. Sriwiriyajan S, Samaeng M, Ridtitid W, Mahatthanatrakul W, Wongnawa M "Pharmacokinetic interactions between ciprofloxacin and itraconazole in healthy male volunteers." Biopharm Drug Dispos 32 (2011): 168-74
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

cilostazol food

Applies to: cilostazol

Take cilostazol on an empty stomach 1 hour before or 2 hours after a meal unless otherwise directed by your doctor. Food may reduce the absorption of cilostazol. Taking cilostazol on an empty stomach will make it easier for your body to absorb the medication. If you are receiving therapy with cilostazol you should avoid grapefruits and grapefruit juice. Grapefruit can raise the levels of cilostazol in your body and lead to dangerous side effects. You may experience headache, dizziness, chest pain, feeling short of breath, and swelling of your ankles or feet. Call your doctor at once if you have any of these symptoms.

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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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