Ketoconazole with Bedaquiline Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Bedaquiline
- Bedaquiline
- Sirturo®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased bedaquiline plasma concentrations and increased risk for QT prolongation
Interaction Summary
Using ketoconazole together with a CYP3A4 substrate known to prolong the QT interval, such as bedaquiline, may be contraindicated. Concomitant use may result in elevated plasma concentrations of bedaquiline, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias including torsades de pointes.. During a study, a greater effect on QTc was observed with repeated dosing of bedaquiline and ketoconazole in combination compared with repeated dosing of the original drugs alone. During a pharmacokinetic study in healthy volunteers, concurrent administration of bedaquiline and ketoconazole significantly increased bedaquiline AUC and Cmax. Avoid concurrent use of bedaquiline with a strong CYP3A4 inhibitor for more than 14 consecutive days, unless the benefits of the combination outweighs the risks. If concomitant administration is required, use caution and monitor ECG. Discontinue all QT prolonging agents if the patient develops clinically significant arrhythmias or a QTcF interval of greater than 500 msec (confirmed on repeat ECG)
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Using ketoconazole together with a CYP3A4 substrate known to prolong the QT interval, such as bedaquiline may be contraindicated. Concomitant use may result in elevated plasma concentrations of bedaquiline, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias including torsades de pointes. If concomitant use is necessary, monitor ECG and discontinue all QT-prolonging agents if the patient develops clinically significant arrhythmias or a QTcF interval of greater than 500 msec (confirmed on repeat ECG). Avoid concurrent use of bedaquiline with a strong CYP3A4 inhibitor such as ketoconazole for more than 14 consecutive days, unless the benefits of the drug combination outweighs the risks .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated bedaquiline metabolism by ketoconazole; additive QT-interval prolongation
Literature Reports
A) In a pharmacokinetic study in healthy subjects, the bedaquiline AUC at 24 hours, Cmax, and minimum concentration were increased by 22% (90% CI, 12% to 32%), 9% (90% CI, -2% to 21%), and 33% (90% CI, 24% to 43%), respectively, during coadministration of bedaquiline 400 mg/day for 14 days and ketoconazole 400 mg/day for 4 days .
Ketoconazole Overview
-
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.
Bedaquiline Overview
-
Bedaquiline is used along with at least three other medications to treat multi-drug resistant tuberculosis (MDR-TB; a serious infection that affects the lungs and other parts of the body and that cannot be treated with other medications that are usually used to treat the condition) in adults and children 5 years and older who weigh at least 33 lbs (15 kg) that has affected the lungs. Bedaquiline should not be used to treat TB that mainly affects other parts of the body. Bedaquiline is in a class of medications called anti-mycobacterials. It works by killing the bacteria that cause MDR-TB.
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.