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Drug Interactions between donepezil and ivacaftor / lumacaftor

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

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Interactions between your drugs

Moderate

donepezil lumacaftor

Applies to: donepezil and ivacaftor / lumacaftor

MONITOR: Coadministration with drugs that are inducers of the CYP450 3A4 and/or 2D6 enzymatic pathways may decrease the plasma concentrations of donepezil. The mechanism is accelerated clearance of donepezil due to enhanced CYP450 activities.

MANAGEMENT: While clinical data are lacking, the possibility of a diminished therapeutic response to donepezil should be considered in patients receiving concomitant inducer agents.

References

  1. (2001) "Product Information. Aricept (donepezil)." Pfizer U.S. Pharmaceuticals

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Minor

donepezil ivacaftor

Applies to: donepezil and ivacaftor / lumacaftor

Coadministration with inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations of donepezil, which is primarily metabolized by these isoenzymes. In a 7-day crossover study in 18 healthy volunteers, the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily) increased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of donepezil (5 mg once daily) by approximately 36% each. The clinical relevance of these increases is unknown. A prolonged duration of monitoring for adverse effects may be required depending on the elimination half-life of the concomitant drug. For example, it should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, can increase plasma concentrations and the risk of adverse effects of donepezil for at least 28 days after administration of rolapitant.

References

  1. (2001) "Product Information. Aricept (donepezil)." Pfizer U.S. Pharmaceuticals
  2. Tiseo PJ, Perdomo CA, Friedhoff LT (1998) "Concurrent administration of donepezil HCl and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses." Br J Clin Pharmacol, 46, p. 30-4
  3. Rojas-Fernandez C, Fisher C (2000) "Drug interactions and donepezil." J Am Geriat Soc, 40, p. 597-8
  4. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.
View all 4 references

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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.

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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