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Drug Interactions between conivaptan and Kalydeco

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

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Interactions between your drugs

Major

conivaptan ivacaftor

Applies to: conivaptan and Kalydeco (ivacaftor)

GENERALLY AVOID: Coadministration with conivaptan may significantly increase the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Conivaptan is a mechanism-based inhibitor of CYP450 3A4. In pharmacokinetic studies with drugs that primarily undergo metabolism by CYP450 3A4 such as midazolam, simvastatin and amlodipine, conivaptan 30 to 40 mg/day has increased systemic exposure (AUC) by 2- to 3-fold.

MANAGEMENT: Concomitant use of conivaptan with sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index should generally be avoided. Subsequent treatment with CYP450 3A4 substrates may be initiated no sooner than 1 week after completion of conivaptan treatment.

References

  1. "Product Information. Vaprisol (conivaptan)." Cumberland Pharmaceuticals Inc (2006):

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Drug and food interactions

Moderate

ivacaftor food

Applies to: Kalydeco (ivacaftor)

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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