Fluconazole with Tofacitinib Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Tofacitinib
- Tofacitinib
- Xeljanz®
- Xeljanz® XR
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased tofacitinib exposure
Interaction Summary
Tofacitinib metabolism is mediated primarily by CYP3A4, and to a lesser extent by CYP2C19. Tofacitinib coadministered with fluconazole (a moderate CYP3A4 inhibitor and potent CYP2C19 inhibitor) significantly increased tofacitinib Cmax and AUC concentrations compared with tofacitinib administered alone. If concomitant use is necessary in patients with rheumatoid arthritis or psoriatic arthritis, adjust the tofacitinib dosage to 5 mg once daily for immediate-release and extended-release formulations. If concomitant use is necessary in patients with ulcerative colitis taking 10 mg twice daily, adjust the tofacitinib dosage to 5 mg twice daily and if taking 5 mg twice daily, reduce to 5 mg once daily and carefully monitor the patient .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of medications that cause both strong inhibition of CYP2C19 and moderate inhibition of CYP3A4 (i.e., fluconazole) with tofacitinib can increase tofacitinib exposure. If concomitant use is necessary in patients with rheumatoid arthritis or psoriatic arthritis, adjust the tofacitinib dosage to 5 mg once daily for immediate-release and extended-release formulations. If concomitant use is necessary in patients with ulcerative colitis taking 10 mg twice daily, adjust the tofacitinib dosage to 5 mg twice daily and if taking 5 mg twice daily, reduce to 5 mg once daily and carefully monitor the patient .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated tofacitinib metabolism; inhibition of CYP2C19-mediated tofacitinib metabolism
Literature Reports
A) Coadministration of fluconazole (400 mg on day 1 and 200 mg once daily for 6 days [days 2-7]) and tofacitinib (30 mg single dose on day 5) in healthy subjects resulted in increased mean tofacitinib AUC and Cmax values of approximately 79% (90% confidence interval (CI), 64% to 96%) and 27% (90% CI, 12% to 44%), respectively, compared to administration of tofacitinib alone .
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.
Tofacitinib Overview
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Tofacitinib is used alone or with other medications to treat rheumatoid arthritis (condition in which the body attacks its own joints causing pain, swelling, and loss of function) in adults who are unable to take or did not respond to one or more tumor necrosis factor (TNF) inhibitor medication(s). It is also used to treat psoriatic arthritis (a condition that causes joint pain and swelling and scales on the skin) in adults who are unable to take or did not respond to or tolerate one or more TNF inhibitor medication(s). Tofacitinib is used to treat ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum) in adults who are unable to take or who did not respond to one or more TNF inhibitor medication(s). It is also used to treat polyarticular juvenile idiopathic arthritis (PJIA; a type of childhood arthritis that affects five or more joints during the first six months of the condition, causing pain, swelling, and loss of function) in children 2 years and older who are unable to take or who did not respond to one or more TNF inhibitor medication(s). Tofacitinib is in a class of medications called Janus kinase (JAK) inhibitors. It works by decreasing the activity of the immune system.
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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.