Ketoconazole with Chlordiazepoxide Interaction Details

Brand Names Associated with Ketoconazole

Brand Names Associated with Chlordiazepoxide

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 02, 2023

Interaction Effect

Decreased chlordiazepoxide clearance and potentially increased chlordiazepoxide toxicity (excessive sedation and prolonged hypnotic effects)

Interaction Summary

Chlordiazepoxide clearance was reduced when administered with ketoconazole. Potential exist for increased chlordiazepoxide concentrations and subsequent chlordiazepoxide toxicity (excessive sedation and prolonged hypnotic effects).

Severity

Moderate

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Concurrent use of chlordiazepoxide and ketoconazole decreases chlordiazepoxide clearance. Monitor for increased chlordiazepoxide toxicity (excessive sedation and prolonged hypnotic effects).

Mechanism Of Interaction

Unknown

Literature Reports

A) Chlordiazepoxide clearance was reduced in a study evaluating the pharmacokinetics of chlordiazepoxide after a single dose of ketoconazole and after a 5-day course of ketoconazole given to healthy subjects. Six subjects received oral ketoconazole 200 mg or 400 mg with chlordiazepoxide 0.6 mg/kg injected intravenously over 5 minutes. After the single dose of ketoconazole, chlordiazepoxide clearance decreased by 20% and volume of distribution by 26%. After 5 days of ketoconazole therapy in 5 subjects, chlordiazepoxide clearance was reduced by 38% and lower concentrations of its metabolite N-desmethylchloridazepoxide were found. Concentrations of the metabolite demoxepam were unchanged. The postulated mechanism of this interaction was partial inhibition by ketoconazole of hepatic oxidative metabolism of chlordiazepoxide and its metabolites .

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.

Chlordiazepoxide Overview

• Chlordiazepoxide is used to relieve anxiety and to control agitation caused by alcohol withdrawal. Chlordiazepoxide is in a class of medications called benzodiazepines. It works by decreasing abnormal electrical activity in the brain.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.