Fluconazole with Rifabutin Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Rifabutin
- Mycobutin®
- Rifabutin
- Talicia (as a combination product containing Amoxicillin, Omeprazole, Rifabutin)
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased rifabutin exposure and potential rifabutin toxicity (uveitis, ocular pain, photophobia, visual disturbances, loss of vision)
Interaction Summary
Concomitant administration of fluconazole with rifabutin may increase the serum levels of rifabutin resulting in an increased risk of uveitis. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored. Fluconazole increases serum concentrations of coadministered rifabutin by approximately 80% . The result is rifabutin toxicity, commonly manifesting as uveitis. The mechanism of this interaction is inhibition by fluconazole of hepatic cytochrome P450 3A4, which is primarily responsible for rifabutin metabolism. Rifabutin apparently has no significant effect on serum concentrations of fluconazole or other pharmacokinetic parameters .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant administration of fluconazole with rifabutin may increase the serum levels of rifabutin resulting in an increased risk of uveitis. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of rifabutin by fluconazole
Literature Reports
A) There have been reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin up to 80%. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered .
B) In an open-label, crossover study, 12 HIV-infected patients on zidovudine maintenance therapy received two weeks of fluconazole 200 mg daily alone, two weeks of fluconazole 200 mg daily plus rifabutin 300 mg daily, and two weeks of rifabutin 300 mg daily alone. Rifabutin area under the concentration-time curve (AUC) increased by 82% from 3025 ng-hour/mL to 5442 ng-hour/mL during concurrent use. AUC of the active metabolite of rifabutin, 25-desacetyl (LM565), increased by 216% from 244 ng-hour/mL to 959 ng-hour/mL. The effect of rifabutin on fluconazole serum concentrations was found to be insignificant .
C) In a retrospective case series where all patients were receiving rifabutin in combination with fluconazole or clarithromycin (22 patients received fluconazole with rifampin), 54 cases of unilateral or bilateral uveitis associated with rifabutin therapy was observed. Between two weeks and seven months following initiation of rifabutin therapy, patients reported ocular pain, photophobia, or loss of vision. Uveitis symptoms generally resolved one to two months after withdrawal of rifabutin and with administration of topical corticosteroids or mydriatic medications .
D) A 62-year-old HIV-infected man with esophageal candidiasis and alcoholic cirrhosis began taking rifabutin 300 mg per day, in addition to a regimen of didanosine, cotrimoxazole, ranitidine, acyclovir, and fluconazole (100 mg daily). Approximately five weeks later, he experienced uveitis of his left eye and, a few days later, uveitis of his right eye. He reported ocular pain, severe itching, a foreign-body sensation, tearing, decreased vision, and photophobia. On examination, he was found to have panuveitis in one eye and, in the other, acute anterior uveitis, moderate vitritis, and fibrin exudate floating in the anterior chamber. Rifabutin was discontinued and six weeks later, his ocular examination was normal .
E) In a study involving 10 human immunodeficiency virus-infected patients given rifabutin, fluconazole and clarithromycin, there was a 76% increase in the area under the concentration-time curve of rifabutin with either fluconazole or clarithromycin administration alone and a 152% increase when both drugs were administered with rifabutin. Four drug courses were given: 1. rifabutin 300 mg once a day; 2. rifabutin and fluconazole 200 mg once a day; 3. rifabutin and clarithromycin 500 mg once a day; and 4. rifabutin, fluconazole, and clarithromycin at the above doses. After the initial dose of rifabutin patients were randomly assigned to take each of the two-drug combinations for 7 days, while the triple drug therapy was administered last. Serial blood samples were collected on the seventh day of each regimen. Each regimen was followed by a 7-day washout, and all the patients received each of the four regimens. Rifabutin both induces and acts as a substrate for the CYP450 enzyme system, specifically CYP3A4. Fluconazole and clarithromycin inhibit CYP3A4. The maximum plasma concentration of rifabutin increased 91% when given with fluconazole, 85% when given with clarithromycin and 149% when given with both .
Fluconazole Overview
-
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.
Rifabutin Overview
-
Rifabutin helps to prevent or slow the spread of Mycobacterium avium complex disease (MAC; a bacterial infection that may cause serious symptoms) in patients with human immunodeficiency virus (HIV) infection. It is also used in combination with other medications to eliminate H. pylori, a bacteria that causes ulcers. Rifabutin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.
-
Antibiotics such as rifabutin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.