Ketoconazole with Rifabutin Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
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
Dec 02, 2023
Interaction Effect
Increased rifabutin exposure and decreased ketoconazole exposure
Interaction Summary
Using ketoconazole together with a potent CYP3A4 inducer such as rifabutin is not recommended and rifabutin should be avoided within 2 weeks of initiating ketoconazole therapy unless the potential benefits outweigh the potential risks. Concomitant use may result in decreased plasma concentrations of ketoconazole via the induction of CYP3A-mediated ketoconazole metabolism, leading to a loss of ketoconazole therapeutic effect. Additionally, ketoconazole is a potent inhibitor of CYP3A4, therefore, concomitant use may lead to increased plasma concentrations of rifabutin due to the inhibition of CYP3A-mediated rifabutin metabolism, increasing the risk for rifabutin adverse effects. While not evaluated with ketoconazole, concurrent administration of other azole antifungal drugs with rifabutin have altered the metabolism of both drugs . If concomitant use is clinically warranted, carefully monitor for increased rifabutin levels or adverse events and for reduced ketoconazole efficacy. Dosage adjustments of rifabutin and or ketoconazole may also be required .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Using ketoconazole together with rifabutin is not recommended and rifabutin should be avoided within 2 weeks of initiating ketoconazole unless the potential benefits outweigh the potential risks. Concomitant use may result in decreased plasma concentrations of ketoconazole leading to a loss of ketoconazole therapeutic effect. Additionally, concomitant use may lead to increased plasma concentrations of rifabutin, increasing the risk for rifabutin adverse effects. If concomitant use is clinically warranted, carefully monitor for increased rifabutin levels or adverse events and for reduced ketoconazole efficacy. Dosage adjustments of rifabutin and/or ketoconazole may also be required.
Mechanism Of Interaction
Inhibition of CYP3A-mediated rifabutin metabolism; induction of CYP3A-mediated ketoconazole metabolism
Literature Reports
A) During drug interaction studies in HIV-infected patients on zidovudine maintenance therapy (n=12), coadministration of fluconazole 200 mg daily and rifabutin 300 mg daily for 2 weeks resulted in an increase in rifabutin AUC and Cmax by 82% and 88%, respectively. In another study of HIV-infected patients (n=6), coadministration of itraconazole 200 mg daily with rifabutin 300 mg daily resulted a decrease of 70% and 75% in rifabutin AUC and Cmax, respectively . In vitro, ketoconazole was shown to inhibit the CYP-mediated metabolism of rifabutin .
Ketoconazole Overview
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Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Rifabutin Overview
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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.
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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.
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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.