Fluconazole with Ivacaftor Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Ivacaftor
- Ivacaftor
- Kalydeco®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased ivacaftor exposure
Interaction Summary
The concomitant use of ivacaftor with the moderate CYP3A inhibitor fluconazole increased ivacaftor AUC by 3-fold. Dose adjustments are required for the concomitant use of ivacaftor or ivacaftor-containing products with moderate CYP3A inhibitors. For Kalydeco(R), reduce the dose to 150 mg orally once daily (6 years or older), or 25 mg (weight, 5 kg to less than 7 kg), 50 mg (7 kg to less than 14 kg) or 75 mg (14 kg or greater) of oral granules once daily in patients 6 months to less than 6 years; concomitant use is not recommended in patients younger than 6 months. For Symdeko(TM), alternate daily dosing starting with tezacaftor 100 mg/ivacaftor 150 mg orally in the morning on day 1, then ivacaftor 150 mg orally in the morning on day 2 . For Trikafta(TM), alternate daily dosing starting with 2 tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) orally in the morning on day 1, then ivacaftor 150 mg orally in the morning on day 2. Continue alternating without evening doses . No dose adjustment is required for concomitant use of Orkambi(R) .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Coadministration of ivacaftor with a moderate CYP3A inhibitor may increase ivacaftor exposure. Dose adjustments are required for the concomitant use of ivacaftor or ivacaftor-containing products with moderate CYP3A inhibitors. For Kalydeco(R), reduce the dose to 150 mg orally once daily (6 years or older), or 25 mg (weight, 5 kg to less than 7 kg), 50 mg (7 kg to less than 14 kg) or 75 mg (14 kg or greater) of oral granules once daily in patients 6 months to less than 6 years; concomitant use is not recommended in patients younger than 6 months. For Symdeko(TM), alternate daily dosing starting with tezacaftor 100 mg/ivacaftor 150 mg orally in the morning on day 1, then ivacaftor 150 mg orally in the morning on day 2 . For Trikafta(TM), alternate daily dosing starting with 2 tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) orally in the morning on day 1, then ivacaftor 150 mg orally in the morning on day 2. Continue alternating without evening doses . No dose adjustment is required for concomitant use of Orkambi(R) .
Mechanism Of Interaction
Inhibition of CYP3A-mediated metabolism of ivacaftor
Literature Reports
A) Simulations indicated that coadministration with moderate CYP3A inhibitors may increase elexacaftor and tezacaftor AUC by approximately 1.9 to 2.3-fold and 2.1-fold, respectively .
B) Coadministration of ivacaftor 150 mg orally twice daily with moderate CYP3A inhibitor fluconazole 400 mg orally x 1 dose on day 1, followed by 200 mg once daily resulted in a 2.95-fold increase in ivacaftor exposure and a 2.47-fold increase in Cmax .
Fluconazole Overview
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Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
Ivacaftor Overview
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Ivacaftor is used to treat certain types of cystic fibrosis (an inborn disease that causes problems with breathing, digestion, and reproduction) in adults and children 4 months of age and older. Ivacaftor should be used only in people with a certain genetic make-up. Your doctor may order a blood test to help decide if this medication is right for you. Ivacaftor is in a class of medications called cystic fibrosis transmembrane conductance regulator (CFTR) potentiators. It works by improving the function of a protein in the body to decrease the build-up of thick mucus in the lungs and improving other symptoms of cystic fibrosis.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.