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Drug Interactions between ivacaftor / lumacaftor and pitolisant

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

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Interactions between your drugs

Major

lumacaftor pitolisant

Applies to: ivacaftor / lumacaftor and pitolisant

ADJUST DOSE: Coadministration with potent CYP450 3A4 inducers may decrease the systemic exposure and efficacy of pitolisant. The proposed mechanism is induction of CYP450 3A4-mediated metabolism of pitolisant, which has been shown to be metabolized by this isoenzyme. Concomitant use with the potent CYP450 3A4 inducer rifampin decreased the mean peak plasma concentration (Cmax) and area under the plasma concentration-time curve ratio (AUC ratio) by 39% and 50%, respectively.

MANAGEMENT: Patients should be assessed for loss of efficacy of pitolisant following initiation of a potent CYP450 3A4 inducer, and the pitolisant dosage adjusted as necessary. For patients already receiving a stable dose of pitolisant 8.9 mg or 17.8 mg once daily, the dose of pitolisant should be increased to double the original daily dose (i.e., 17.8 mg or 35.6 mg, respectively) over 7 days. The dosage of pitolisant should be reduced by half if concomitant use of a strong CYP450 3A4 inducer is discontinued.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2019) "Product Information. Wakix (pitolisant)." Harmony Biosciences, LLC

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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.