Fluconazole with Ruxolitinib Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Ruxolitinib
- Jakafi
- Ruxolitinib
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 27, 2023
Interaction Effect
Increased ruxolitinib exposure and adverse effects
Interaction Summary
Concomitant use of fluconazole with ruxolitinib may lead to increased ruxolitinib plasma levels and adverse effects due to inhibition by fluconazole of the CYP3A4 and CYP2C9 metabolic pathways of ruxolitinib. Avoid concurrent use of ruxolitinib with fluconazole doses higher than 200 mg/day, except in patients with acute graft verses host disease. No dosage adjustments are needed in patients with acute graft versus host disease. For all other indications, if concurrent use is required with fluconazole doses of up to 200 mg/day, ruxolitinib dose modifications are required. In patients with myelofibrosis and a platelet count of 100 x 10(9)/L or more, initiate with ruxolitinib 10 mg twice daily; for platelet counts of 50 to less than 100 x 10(9)/L, initiate with ruxolitinib 5 mg once daily. In patients with polycythemia vera, initiate with ruxolitinib 5 mg twice daily. In patients treated with stable ruxolitinib doses for myelofibrosis or polycythemia vera, reduce the ruxolitinib 10-mg twice-daily dose by 50% or reduce the 5-mg twice-daily dose to 5 mg once daily; if already receiving 5 mg once daily, avoid concomitant use until fluconazole is discontinued .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concurrent use of ruxolitinib with fluconazole doses higher than 200 mg/day, except in patients with acute graft verses host disease. No dosage adjustments are needed in patients with acute graft versus host disease. For all other indications, if concurrent use is required with fluconazole doses of up to 200 mg/day, ruxolitinib dose modifications are required. In patients with myelofibrosis and a platelet count of 100 x 10(9)/L or more, initiate with ruxolitinib 10 mg twice daily; for platelet counts of 50 to less than 100 x 10(9)/L, initiate with ruxolitinib 5 mg once daily. In patients with polycythemia vera, initiate with ruxolitinib 5 mg twice daily. In patients treated with stable ruxolitinib doses for myelofibrosis or polycythemia vera, reduce the ruxolitinib 10-mg twice-daily dose by 50% or reduce the 5-mg twice-daily dose to 5 mg once daily; if already receiving 5 mg once daily, avoid concomitant use until fluconazole is discontinued.
Mechanism Of Interaction
Inhibition of CYP3A4- and CYP2C9-mediated ruxolitinib metabolism by fluconazole
Literature Reports
A) In an open-label, 2-period fixed sequence study of healthy adults (N=15), concurrent use of ruxolitinib with fluconazole significantly increased ruxolitinib Cmax, AUC(last), and AUC(inf) by 47%, 234%, and 232%, respectively, compared with ruxolitinib alone. Apparent clearance decreased approximately 3-fold and t(1/2) increased approximately 2.5-fold. No adverse events attributed to ruxolitinib were reported. In period 1, ruxolitinib 10 mg orally was administered alone on day 1 and coadministered with fluconazole during period 2 with a washout period of at least 1 day. Fluconazole was administered as a loading dose of 400 mg orally on day 2, then 200 mg daily for 7 days (day 3 through 9; including ruxolitinib coadministration on day 7). Systemic exposure was evaluated on day 10. The median age of enrolled subjects was 44 years, 86.7% were male, and median BMI was 25.28 kg/m(2) .
B) Through pharmacokinetic modeling, ruxolitinib AUC is predicted to increased by 100 to 300 percent with the addition of fluconazole 100 mg to 400 mg/day to a ruxolitinib 20 mg/day regimen .
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.
Ruxolitinib Overview
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Ruxolitinib is used to treat myelofibrosis (a cancer of the bone marrow in which the bone marrow is replaced by scar tissue and causes decreased blood cell production). It is also used to treat polycythemia vera (PV; a slow growing cancer of the blood in which the bone marrow makes too many red blood cells) in people who were not able to be treated successfully with hydroxyurea. Ruxolitinib is also used to treat acute graft versus host disease (aGVHD; a complication of hematopoietic stem-cell transplant [HSCT; a procedure that replaces diseased bone marrow with healthy bone marrow] that usually develops within the first months after HSCT) in adults and children 12 years of age and older who were treated unsuccessfully with steroid medications. It is also used to treat chronic GVHD (cGVHD; a complication of HSCT that usually develops at least 3 months after HSCT) in adults and children 12 years of age and older who were treated unsuccessfully with 1 or 2 other treatments. Ruxolitinib is in a class of medications called kinase inhibitors. It works to treat myelofibrosis and PV by blocking the signals that cause cancer cells to multiply. This helps to stop the spread of cancer cells. It works to treat GVHD by blocking the signals of the cells that cause GVHD.
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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.