Drug Interactions between crinecerfont and repotrectinib
This report displays the potential drug interactions for the following 2 drugs:
- crinecerfont
- repotrectinib
Interactions between your drugs
repotrectinib crinecerfont
Applies to: repotrectinib and crinecerfont
ADJUST DOSE: Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of crinecerfont, which is primarily metabolized by the isoenzyme. Concomitant use with rifampin, a potent CYP450 3A4 inducer, decreased crinecerfont peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 62%, respectively. No data are available for other, less potent inducers. Reduced efficacy of crinecerfont may occur.
MANAGEMENT: When coadministered with moderate CYP450 3A4 inducers, the crinecerfont evening dose should be increased.
In adults, increase the crinecerfont dose to 200 mg with a meal in the evening (morning dose of 100 mg with a meal remains unchanged).
In pediatric patients 4 years of age and older, increase the crinecerfont dose based on weight:
-Patients weighing 10 kg to less than 20 kg: 50 mg with a meal in the evening (morning dose of 25 mg with a meal remains unchanged)
-Patients weighing 20 kg to less than 55 kg: 100 mg with a meal in the evening (morning dose of 50 mg with a meal remains unchanged)
-Patients weighing 55 kg or more: 200 mg with a meal in the evening (morning dose of 100 mg with a meal remains unchanged)
References (1)
- (2024) "Product Information. Crenessity (crinecerfont)." Neurocrine Biosciences, Inc.
Drug and food interactions
repotrectinib food
Applies to: repotrectinib
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and adverse effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-gp in vitro. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with repotrectinib and grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Drug interaction studies have shown that the administration of repotrectinib with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 1.7-fold and 5.9-fold, respectively. 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 exposure to repotrectinib may increase the risk of adverse reactions such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and dyspnea as well as more serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, myalgia with creatinine phosphokinase (CPK) elevation, hyperuricemia, and skeletal fractures.
MANAGEMENT: The manufacturer advises that concomitant use of repotrectinib with grapefruit, grapefruit juice, or supplements that contain grapefruit should be avoided.
References (1)
- (2023) "Product Information. Augtyro (repotrectinib)." Bristol-Myers Squibb
crinecerfont food
Applies to: crinecerfont
ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of crinecerfont. Administration of crinecerfont capsules and oral solution with a high-fat meal (800 to 1000 calories, 50% fat), increased crinecerfont peak plasma concentration (Cmax) by 4.9-fold and 8.6-fold, respectively, and systemic exposure (AUC) by 3.3-fold and 8.3-fold, respectively, compared to administration under fasting conditions.
MANAGEMENT: Crinecerfont should be administered twice daily with a meal in the morning and evening without regard to fat or calorie content.
References (1)
- (2024) "Product Information. Crenessity (crinecerfont)." Neurocrine Biosciences, 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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
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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