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Drug Interactions between asciminib and buspirone

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

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Interactions between your drugs

Moderate

busPIRone asciminib

Applies to: buspirone and asciminib

MONITOR: Coadministration with asciminib may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 3A4 by asciminib. When midazolam, a sensitive CYP450 3A4 substrate, was coadministered with asciminib 40 mg twice daily, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 11% and 28%, respectively. Likewise, the Cmax and AUC of midazolam increased by 17% and 24%, respectively, following coadministration with asciminib at 80 mg once daily, but increased by 58% and 88%, respectively, following coadministration with asciminib at 200 mg twice daily. These results suggest weak inhibition of CYP450 3A4 by asciminib.

MANAGEMENT: Caution is advised when asciminib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever asciminib is added to or withdrawn from therapy. The prescribing information recommends closely monitoring for the development of adverse reactions in patients receiving asciminib therapy at 80 mg total daily dose with certain CYP450 3A4 substrates where minimal concentration changes may lead to serious or life-threatening toxicities, and avoiding coadministration of these drugs with asciminib at the maximum recommended dosage of 200 mg twice daily. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a weak CYP450 3A4 inhibitor like asciminib and for any dosage adjustments that may be required.

References (1)
  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals

Drug and food interactions

Moderate

busPIRone food

Applies to: buspirone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of buspirone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: In a small, randomized, crossover study, the consumption of large amounts of grapefruit juice (compared to water) was associated with significantly increased plasma buspirone concentrations, slightly prolonged elimination half-lives, and delayed times to reach peak drug concentration. The perceived pharmacodynamic effect of buspirone, as measured by subjective drowsiness and overall subjective drug effect, was also enhanced by grapefruit juice. These alterations may stem from the delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving buspirone should be advised to avoid consumption of alcohol. Patients also should preferably avoid the consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. If this is not possible, the buspirone dose should be taken at least 2 hours before or 8 hours after grapefruit or grapefruit juice. Monitoring for increased CNS depression is recommended.

References (3)
  1. (2002) "Product Information. Buspar (buspirone)." Bristol-Myers Squibb
  2. Lilja JJ, Kivisto KT, Backman JT, Lamberg TS, Neuvonen PJ (1998) "Grapefruit juice substantially increases plasma concentrations of buspirone." Clin Pharmacol Ther, 64, p. 655-60
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
Moderate

asciminib food

Applies to: asciminib

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

MANAGEMENT: To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.

References (2)
  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals
  2. (2022) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals UK Ltd, Scemblix 20 mg film-

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

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