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Drug Interactions between ivacaftor / lumacaftor and quizartinib

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

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Interactions between your drugs

Major

lumacaftor quizartinib

Applies to: ivacaftor / lumacaftor and quizartinib

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of quizartinib and its major circulating active metabolite, AC886. According to the prescribing information, quizartinib is primarily metabolized via oxidation by CYP450 3A4/5 in vitro, and AC886 is formed and metabolized by CYP450 3A4/5. Following coadministration of a single 53 mg dose of quizartinib with efavirenz, a moderate CYP450 3A4 inducer, quizartinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 45% and 90%, respectively, while the Cmax and AUC of AC886 decreased by 68% and 96%, respectively. Reduced effectiveness of quizartinib may occur. Coadministration with a potent CYP450 3A4 inducer has not been studied, but similar if not even greater reductions in quizartinib and AC886 exposures should be expected.

MANAGEMENT: Concomitant use of quizartinib with potent or moderate CYP450 3A4 inducers should generally be avoided.

References

  1. (2023) "Product Information. Vanflyta (quizartinib)." Daiichi Sankyo, Inc.

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Minor

ivacaftor quizartinib

Applies to: ivacaftor / lumacaftor and quizartinib

Coadministration with mild or moderate inhibitors of CYP450 3A4 is not expected to have clinically significant effects on the pharmacokinetics of quizartinib or its major circulating active metabolite, AC886. According to the prescribing information, quizartinib is primarily metabolized via oxidation by CYP450 3A4/5 in vitro, and AC886 is formed and metabolized by CYP450 3A4/5. Following coadministration of a single 53 mg dose of quizartinib with ketoconazole, a potent CYP450 3A4 inhibitor, quizartinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 17% and 94%, respectively, while the Cmax and AUC of AC886 decreased by 60% and 94%, respectively. By contrast, clinically significant changes in the Cmax and AUC of quizartinib and AC886 were not observed following coadministration of single-dose quizartinib with fluconazole, a moderate CYP450 3A4 inhibitor. Therefore, no dosage adjustments are recommended when quizartinib is coadministered with mild and moderate CYP450 3A4 inhibitors.

References

  1. (2023) "Product Information. Vanflyta (quizartinib)." Daiichi Sankyo, Inc.

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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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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.

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