Ketoconazole with Vardenafil Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Vardenafil
- Levitra®
- Staxyn®
- Vardenafil
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased vardenafil exposure and an increased risk of QT interval prolongation
Interaction Summary
Ketoconazole is a strong CYP3A4 inhibitor that may prolong the QT interval. Coadministration of ketoconazole with CYP3A4 substrates that are known to prolong the QT interval is contraindicated. Coadministration of ketoconazole, a potent CYP3A4 inhibitor, with vardenafil, a CYP3A4 substrate, led to increased vardenafil concentrations in a clinical study . Use of the orally disintegrating tablet formulation of vardenafil is not recommended with ketoconazole . In addition, both agents are known to prolong the QT interval . Concomitant use may result in additive effects on the QT interval, increasing the risk for serious ventricular arrhythmias including torsades de pointes. If concomitant use of ketoconazole with vardenafil film-coated tablets, use caution and do not to exceed vardenafil 5 mg every 24 hours if given with ketoconazole 200 mg, or vardenafil 2.5 mg every 24 hours if given with ketoconazole 400 mg .
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Ketoconazole is a strong CYP3A4 inhibitor that may prolong the QT interval. Coadministration of ketoconazole with CYP3A4 substrates that are known to prolong the QT interval is contraindicated. Concomitant use of ketoconazole and vardenafil may increase vardenafil plasma concentrations. Use of the orally disintegrating tablet formulation of vardenafil is not recommended with potent CYP3A4 inhibitors, such as ketoconazole . In addition, both agents are known to prolong the QT interval . Concomitant use may result in additive effects on the QT interval, increasing the risk for serious ventricular arrhythmias including torsades de pointes. If concomitant use of ketoconazole and vardenafil film-coated tablets is indicated, use caution and do not exceed 5 vardenafil mg every 24 hours if given with ketoconazole 200 mg, or vardenafil 2.5 mg every 24 hours if given with ketoconazole 400 mg .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated vardenafil metabolism by ketoconazole; additive QT interval prolongation
Literature Reports
A) In a pharmacokinetic study in healthy volunteers, coadministration of ketoconazole 200 mg daily with a single dose of vardenafil 5 mg resulted in a 4-fold increase in the vardenafil Cmax and a 10-fold increase in the vardenafil AUC compared with use of vardenafil alone .
B) In a single-dose, double-blind, randomized, placebo- and active-controlled crossover study, 59 male patients receiving vardenafil 10 mg (therapeutic), vardenafil 80 mg (supratherapeutic), or moxifloxacin 400 mg experienced similar increases in QTc interval measurements taken one hour after dosing. Single-dose administration resulted in a placebo-subtracted mean change from baseline QT (uncorrected) of 3 msec (90% confidence interval [CI]: 1, 5) for moxifloxacin 400 mg and -2 msec (90% CI: -4, 0) for both vardenafil 10 mg and 80 mg. Mean change from baseline Fridericia QT correction was 10 msec (90% CI: 8, 11) for vardenafil 80 mg, and 8 msec (90% CI: 6, 9) for both vardenafil 10 mg and moxifloxacin. Mean change from baseline for individual QT correction was 4 msec (90% CI: 3, 6) for vardenafil 10 mg, 6 msec (90% CI: 4, 7) for vardenafil 80 mg, and 7 msec (90% CI: 5, 8) for moxifloxacin. Mean increases in heart rate with vardenafil 10 mg and 80 mg were 5 and 6 beats per minute, respectively, compared with placebo .
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.
Vardenafil Overview
-
Vardenafil is used to treat erectile dysfunction (impotence; inability to get or keep an erection) in men. Vardenafil is in a class of medications called phosphodiesterase (PDE) inhibitors. It works by increasing blood flow to the penis during sexual stimulation. This increased blood flow can cause an erection. Vardenafil does not cure erectile dysfunction or increase sexual desire. Vardenafil does not prevent pregnancy or the spread of sexually transmitted diseases such as human immunodeficiency virus (HIV).
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.