Ketoconazole with Quinine Interaction Details


Brand Names Associated with Ketoconazole

  • Ketoconazole
  • Nizoral®

Brand Names Associated with Quinine

  • Qualaquin®
  • Quinine

Medical Content Editor
Last updated Dec 02, 2023


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Interaction Effect

Increased quinine plasma concentrations and risk of QT interval prolongation


Interaction Summary

Using ketoconazole together with a CYP3A4 substrate known to prolong the QT interval, such as quinine, may be contraindicated. Concomitant use may result in elevated plasma concentrations of quinine, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias, including torsades de pointes. Peak plasma concentrations of quinine, a CYP3A4 substrate and inhibitor, have been shown to correspond to maximal increase in the QT interval. Concomitant use of ketoconazole and quinine resulted in an increased AUC (mean, 45%) and decreased clearance (mean, 31%) of quinine in a study of 9 healthy subjects. If concomitant use of ketoconazole and quinine is clinically warranted, monitor the patient closely for adverse reactions  and consider monitoring baseline and on-treatment 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 quinine, may be contraindicated. Concomitant use may result in elevated plasma concentrations of quinine, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias, including torsades de pointes. If concomitant use of ketoconazole and quinine is clinically warranted, monitor the patient closely for adverse reactions  and consider monitoring baseline and on-treatment ECG.


Mechanism Of Interaction

Inhibition of CYP3A-mediated quinine metabolism; additive QT-interval prolongation


Literature Reports

A) Concomitant use of quinine hydrochloride (500 mg single dose) and ketoconazole (100 mg twice daily for 3 days) in 9 healthy subjects resulted in a mean 45% increase in quinine AUC and a mean 31% reduction in quinine clearance compared with quinine alone .

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

Quinine Overview

  • Quinine is used alone or with other medications to treat malaria (a serious or life-threatening illness that is spread by mosquitos in certain parts of the world). Quinine should not be used to prevent malaria. Quinine is in a class of medications called antimalarials. It works by killing the organisms that cause malaria.

See More information Regarding Quinine

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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.