Fluconazole with Rifampin Interaction Details

Brand Names Associated with Fluconazole

Brand Names Associated with Rifampin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 27, 2023

Interaction Effect

Reduced fluconazole exposure and antifungal activity

Interaction Summary

Concurrent administration of fluconazole and rifAMPin results in enhanced metabolism of fluconazole, potentially reducing fluconazole effective inhibitory serum concentrations. Consider increasing the fluconazole dose when it is used concomitantly with rifAMPin .

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant administration of fluconazole with rifAMPin may increase the metabolism of fluconazole resulting in decreased fluconazole serum concentrations and efficacy. Consider increasing the fluconazole dose when it is used concomitantly with rifAMPin.

Mechanism Of Interaction

Increased hepatic metabolism of fluconazole

Literature Reports

A) The bioavailability of fluconazole was significantly reduced when rifampicin (rifAMPin) was added to a stable regimen of fluconazole. Patients infected with human immunodeficiency virus (HIV) who were receiving fluconazole antifungal therapy (400 milligrams (mg) once daily; n=12) for cryptococcal meningitis were compared with HIV and cryptococcal-infected patients receiving concomitant treatment with fluconazole and rifampicin 600 mg once daily (for at least 2 weeks prior to study entry) for the treatment of tuberculosis (n=12). All patients had received initial antifungal treatment with a 2-week regimen of amphotericin 0.7 mg/kilogram/day prior to converting to oral antifungal treatment. Fluconazole pharmacokinetics were assessed over a 24-hour period on study days 8 and 15. Patients receiving concomitant therapy with fluconazole and rifampicin experienced significant reductions, at all time-points, in fluconazole maximum serum concentration (Cmax), area under the concentration-time curve (AUC 0-24 hours), and serum half-life (T1/2); by 17%, 22%, and 28%, respectively; p=0.009, 0.001, and less than 0.001, respectively). Similar reductions in fluconazole bioavailability (Cmax, AUC, T1/2) were observed at day 15 of treatment. Differences in conversion rates of cerebral spinal fluid cultures were not significantly different between the two groups, and all patients had negative cultures at 6 weeks. Patients were later placed on cryptococcal meningitis prophylaxis with fluconazole 200 mg daily. Concurrent treatment with rifampicin reduced fluconazole minimum (trough) serum concentrations to a level bordering upon the reported values for the 50% inhibitory concentration (MIC50) of Cryptococcus neoformans, rendering cotreated patients at risk for loss of effective cryptococcal prophylaxis .

B) In a drug interaction study, administration of a single oral 200 mg dose of fluconazole after 15 days of rifAMPin administered as 600 mg daily in eight healthy male volunteers resulted in a significant decrease in fluconazole AUC and a significant increase in apparent oral clearance of fluconazole. There was a mean +/- SD reduction in fluconazole AUC of 23% (+/- 9% range, -13% to -42%). Apparent oral clearance of fluconazole increased 32% (+/- 17% range, 16% to 72%). Fluconazole half-life decreased from 33.4 +/- 4.4 hours to 26.8 +/- 3.9 hours .

C) Concomitant administration of rifAMPin 600 mg and fluconazole 200 mg resulted in reduction of the fluconazole half-life from 32.9 hours to 26.3 hours in healthy volunteers. The area under the plasma concentration-time curve was reduced by 23%. The peak plasma concentration was not significantly reduced. Patients receiving rifAMPin may require higher doses of fluconazole due to increased metabolism .

D) Three patients with cryptococcal meningitis were treated with fluconazole but experienced clinical relapse that might be due to a drug interaction between fluconazole and rifAMPin .

E) The fluconazole area under the concentration-time curve (AUC) during combined fluconazole- rifAMPin therapy was 56.1% of the fluconazole AUC with single-drug use . The patient had AIDS, along with an infection of Mycobacterium avium/M. intracellulare. However, it was noted that the decrease in fluconazole serum levels did not appear to be as great as those reductions seen in ketoconazole and itraconazole serum concentrations when those azole-type antifungals were given concomitantly with rifAMPin in other patients.

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.

Rifampin Overview

• Rifampin is used with other medications to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Rifampin is also used to treat some people who have Neisseria meningitidis (a type of bacteria that can cause a serious infection called meningitis) infections in their noses or throats. These people have not developed symptoms of the disease, and this treatment is used to prevent them from infecting other people. Rifampin should not be used to treat people who have developed symptoms of meningitis. Rifampin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.

• Antibiotics such as rifampin 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.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.