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Drug Interactions between asciminib and ivacaftor / lumacaftor

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

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Interactions between your drugs

Moderate

ivacaftor asciminib

Applies to: ivacaftor / lumacaftor 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever asciminib is added to or withdrawn from therapy.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. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals

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Moderate

lumacaftor asciminib

Applies to: ivacaftor / lumacaftor and asciminib

MONITOR: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of asciminib. Asciminib is primarily metabolized by CYP450 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT) 2B7- and 2B17-mediated glucuronidation. When a single 40 mg dose of asciminib was coadministered with rifampin, a potent CYP450 3A4 inducer, asciminib peak plasma concentration (Cmax) increased by 9% while its systemic exposure (AUC) decreased by 14.9%. According to physiologically-based pharmacokinetic (PBPK) models, coadministration of asciminib 80 mg once daily and rifampin is predicted to reduce asciminib Cmax and AUC by 23% and 52%, respectively, while coadministration of asciminib 200 mg twice daily and rifampin is predicted to reduce asciminib Cmax and AUC by 47% and 63%, respectively.

MANAGEMENT: Caution is advised when asciminib is prescribed with potent CYP450 3A4 inducers such as carbamazepine, phenobarbital, phenytoin, and St. John's wort. According to some authorities, dose adjustment of asciminib is not required.

References

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

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Drug and food interactions

Moderate

ivacaftor food

Applies to: ivacaftor / lumacaftor

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
View all 4 references

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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

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

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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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