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Drug Interactions between buspirone and repotrectinib

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

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Interactions between your drugs

Moderate

busPIRone repotrectinib

Applies to: buspirone and repotrectinib

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of buspirone, which is primarily metabolized by the isoenzyme. Conversely, discontinuation of an inducer may increase buspirone plasma concentrations and increase the risk of central nervous system depression and other adverse effects. When a single 30 mg dose of buspirone was administered following treatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 5 days) in 10 healthy volunteers, mean buspirone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 84% and 90%, respectively, compared to administration following placebo. None of the subjects had a measurable plasma buspirone concentration at 6, 8 or 10 hours after given rifampin, while buspirone concentration could be determined up to 10 hours in all subjects after placebo. Pharmacodynamic effects of buspirone were also significantly reduced by rifampin in the study. Similar results were reported in another pharmacokinetic study conducted by the same group of investigators.

MANAGEMENT: The potential for diminished pharmacologic effects of buspirone should be considered during coadministration with CYP450 3A4 inducers. Pharmacologic response to buspirone should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the buspirone dosage adjusted as necessary.

References

  1. "Product Information. Buspar (buspirone)." Bristol-Myers Squibb PROD (2002):
  2. Lamberg TS, Kivisto KT, Neuvonen PJ "Concentrations and effects of buspirone are considerably reduced by rifampicin." Br J Clin Pharmacol 45 (1998): 381-5
  3. Kivisto KT, Lamberg TS, Neuvonen PJ "Interactions of buspirone with itraconazole and rifampicin: Effects on the pharmacokinetics of the active 1-(2-pyrimidinyl)-piperazine metabolite of buspirone." Pharmacol Toxicol 84 (1999): 94-7

Drug and food interactions

Major

repotrectinib food

Applies to: repotrectinib

Consumer information for this interaction is not currently available.

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. "Product Information. Augtyro (repotrectinib)." Bristol-Myers Squibb ORIG-1 (2023):
Moderate

busPIRone food

Applies to: buspirone

You should avoid the use of alcohol while being treated with busPIRone. Alcohol can increase the nervous system side effects of busPIRone such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. Patients receiving busPIRone should preferably avoid the consumption of large amounts of grapefruits and grapefruit juice. If this is not possible, the busPIRone dose should be taken at least 2 hours before or 8 hours after grapefruit or grapefruit juice. Large amounts of grapefruit and grapefruit juice may cause increased levels of busPIRone in your body. This can lead to increased adverse effects such as drowsiness. 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.


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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.