Ketoconazole with Telaprevir Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Telaprevir
- Incivek®
- Telaprevir
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased ketoconazole and/or telaprevir plasma concentrations; increased risk for QT interval prolongation
Interaction Summary
Using ketoconazole together with a CYP3A4 substrate known to prolong the QT interval, such as telaprevir, may be contraindicated. Concomitant use may result in elevated plasma concentrations of telaprevir, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias, including torsades de pointes. In addition ketoconazole has also been shown to prolong the QT interval and coadministration of ketoconazole and telaprevir may increase plasma concentrations of both ketoconazole and telaprevir, thereby further increasing the risk for serious adverse effects, including QT interval prolongation. In pharmacokinetic studies, concomitant administration of ketoconazole (a potent CYP3A4 inhibitor) and telaprevir (CYP3A4 substrate and inhibitor) led to increased plasma concentrations of both substances. If concomitant use is required, the daily dose of ketoconazole should not exceed 200 mg .
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 telaprevir, may be contraindicated. Concomitant use may result in elevated plasma concentrations of telaprevir, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias, including torsades de pointes. In addition, ketoconazole has also been shown to prolong the QT interval and coadministration of ketoconazole and telaprevir may increase plasma concentrations of both ketoconazole and telaprevir, thereby further increasing the risk for serious adverse effects, including QT interval prolongation. When coadministration of ketoconazole and telaprevir is necessary, the daily dose of ketoconazole should not exceed 200 mg .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of either drug; additive/increased effects on the QT interval
Literature Reports
A) In a pharmacokinetic study, following a single-dose of ketoconazole 400 mg given concomitantly with a single-dose of telaprevir 750 mg orally, mean ratio estimates of telaprevir AUC and Cmax were increased compared with administration of telaprevir alone (ratio estimates, 1.62; 90% confidence interval (CI), 1.45 to 1.81 and 1.24; 90% CI, 1.1 to 1.41, respectively). In addition, the mean ratio estimate of ketoconazole AUC was increased when a single ketoconazole 200 or 400 mg dose was given to patients receiving telaprevir 1250 mg every 8 hours for 4 days (ratio estimates, 2.25; 90% CI, 1.93 to 2.61 and 1.46; 90% CI, 1.35 to 1.58, respectively); corresponding mean ratio estimate of ketoconazole Cmax were 1.75 (90% CI, 1.51 to 2.03) and 1.23 (90% CI, 1.14 to 1.33), respectively). No changes were observed in the mean ratio estimate of Cmin for either ketoconazole or telaprevir .
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.
Telaprevir Overview
-
Telaprevir is used along with two other medications (ribavirin [Copegus, Rebetol] and peginterferon alfa [Pegasys]) to treat chronic hepatitis C (an ongoing viral infection that damages the liver) in people who have not yet been treated for this condition or whose condition could not successfully be treated with ribavirin and peginterferon alfa alone. Telaprevir is in a class of medications called protease inhibitors. It works by decreasing the amount of hepatitis C virus (HCV) in the body. Telaprevir may not prevent the spread of hepatitis C to other people.
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.