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Drug Interactions between ivacaftor / lumacaftor and zafirlukast

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

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Interactions between your drugs

Moderate

zafirlukast ivacaftor

Applies to: zafirlukast and ivacaftor / lumacaftor

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. The interaction occurs to a greater extent when ivacaftor is administered as monotherapy than when administered in combination with lumacaftor, a potent CYP450 3A4 inducer. In study subjects, ivacaftor systemic exposure (AUC) increased by 8.5-fold when it was administered concomitantly with the potent CYP450 3A4 inhibitor ketoconazole and by 3-fold with the moderate CYP450 3A4 inhibitor fluconazole. By contrast, when lumacaftor/ivacaftor was coadministered with the potent CYP450 3A4 inhibitor itraconazole, ivacaftor peak plasma concentration (Cmax) and AUC increased by an average of 3.7- and 4.3-fold, respectively, and when coadministered with the moderate CYP450 3A4 inhibitor ciprofloxacin, ivacaftor Cmax and AUC increased by just 29% each.

MANAGEMENT: Caution is advised if ivacaftor is used with CYP450 3A4 inhibitors. A dosage adjustment for ivacaftor may be required if undue adverse effects occur.

References

  1. "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals (2012):
  2. "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals (2015):

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Moderate

zafirlukast lumacaftor

Applies to: zafirlukast and ivacaftor / lumacaftor

MONITOR: Coadministration with lumacaftor may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4, 2B6, 2C19, 2C8, and/or 2C9. Lumacaftor is a potent inducer of CYP450 3A4 in vivo. Coadministration of lumacaftor with ivacaftor, a sensitive CYP450 3A4 substrate, decreased ivacaftor systemic exposure (AUC) by approximately 80%. In vitro, lumacaftor is an inducer of several other CYP450 isoenzymes including CYP450 2B6, 2C19, 2C8 and 2C9, although inhibition of the latter two isoenzymes has also been observed in vitro. Drugs that are substrates of CYP450 2C8 and 2C9 (e.g., sulfonylureas and other hypoglycemic agents, warfarin) may demonstrate decreased or increased exposures.

MANAGEMENT: Caution is advised when lumacaftor/ivacaftor is prescribed with drugs that undergo metabolism by CYP450 3A4, 2B6, 2C19, 2C8 and/or 2C9, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lumacaftor/ivacaftor is added to or withdrawn from therapy.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals (2015):
  4. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
View all 4 references

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Drug and food interactions

Moderate

zafirlukast food

Applies to: zafirlukast

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of zafirlukast. In two separate studies, one using a high-fat and the other a high-protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.

MANAGEMENT: To ensure maximal oral absorption, zafirlukast should be administered at least 1 hour before or 2 hours after meals.

References

  1. "Product Information. Accolate (zafirlukast)." Astra-Zeneca Pharmaceuticals PROD (2001):

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

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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