Ketoconazole with Venlafaxine Interaction Details


Brand Names Associated with Ketoconazole

  • Ketoconazole
  • Nizoral®

Brand Names Associated with Venlafaxine

  • Effexor®
  • Effexor® XR
  • Venlafaxine

Medical Content Editor
Last updated Dec 02, 2023


Curious for more information about this interaction?

Ask our pharmacists directly!

Reach out to us

Interaction Effect

Increased venlafaxine exposure and its active metabolite and an increased risk for QT interval prolongation


Interaction Summary

Caution is advised when using ketoconazole together with venlafaxine as both agents are known to prolong the QT interval and concomitant use may result in additive effects on the QT interval, increasing the risk for serious ventricular arrhythmias including torsades de pointes. In addition, coadministration of venlafaxine with CYP3A4 inhibitors increases the exposure of venlafaxine and O-desmethylvenlafaxine which may increase the risk of toxicity of venlafaxine. Consider reducing the dose of venlafaxine. A pharmacokinetic study demonstrated an increase in Cmax and AUC of both venlafaxine and the O-desvenlafaxine active metabolite with concomitant use .


Severity

Major


Onset

Unspecified


Evidence

Established


How To Manage Interaction

Caution is advised when using ketoconazole together with venlafaxine as both agents are known to prolong the QT interval and concomitant use may result in additive effects on the QT interval, increasing the risk for serious ventricular arrhythmias including torsades de pointes. In addition, coadministration of venlafaxine with CYP3A4 inhibitors increases the exposure of venlafaxine and O-desmethylvenlafaxine which may increase the risk of toxicity of venlafaxine. Consider reducing the dose of venlafaxine .


Mechanism Of Interaction

Inhibition of CYP3A-mediated metabolism of venlafaxine and its active metabolite; reduced venlafaxine clearance; additive QT interval prolongation


Literature Reports

A) Higher plasma concentrations of both venlafaxine and the active metabolite O-desvenlafaxine (ODV) occurred during a pharmacokinetic study of ketoconazole 100 mg twice daily plus a single dose of venlafaxine (50 mg to 14 extensive metabolizers (EM) and 25 mg to 6 poor metabolizers (PM)). The Cmax of venlafaxine increased by 48% in PM and 26% in EM. Cmax of ODV increased by 29% in PM and 14% in EM subjects. Venlafaxine AUC increased by 70% (range, -2% to 206%) and 21% in PM and EM subjects, respectively. The ODV metabolite AUC increased by 33% (range, -38% to 105%) and 23% in PM and EM subjects, respectively, and the combined AUCs of venlafaxine plus ODV increased an average of 53% (range, 4% to 134%) and 23%, respectively .

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.

See More information Regarding Ketoconazole

Venlafaxine Overview

  • Venlafaxine is used to treat depression. Venlafaxine extended-release (long-acting) capsules are also used to treat generalized anxiety disorder (GAD; excessive worrying that is difficult to control), social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life), and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Venlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance.

See More information Regarding Venlafaxine

Return To Our Drug Interaction Homepage


Feedback, Question Or Comment About This Information?

Ask , 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.