Ketoconazole with Efavirenz Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Efavirenz
- Atripla® (as a combination product containing Efavirenz, Emtricitabine, Tenofovir)
- Efavirenz
- Sustiva®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Decreased ketoconazole plasma concentrations and an increased risk of QT interval prolongation
Interaction Summary
Using ketoconazole together with a strong CYP3A4 inducer such as efavirenz is not recommended and should be avoided within 2 weeks of initiating ketoconazole, unless the potential benefits outweigh potential risks. Concomitant use may cause decreased ketoconazole plasma concentrations resulting in decreased ketoconazole efficacy. In a pharmacokinetic interaction study, efavirenz had a strong inducing effect on the metabolism of ketoconazole, causing significant decreases in ketoconazole Cmax and AUC and increasing ketoconazole clearance . Consider alternative antifungal treatment in a patient receiving efavirenz, as no recommendations for dose adjustments of ketoconazole are available. Also consider alternatives to efavirenz in a patient already taking another drug that prolongs the QT interval, such as ketoconazole, as additive effects on the QT interval may occur . If concomitant use is required, monitor antifungal response as ketoconazole dosage adjustments may be necessary .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Using ketoconazole together with a strong CYP3A4 inducer such as efavirenz is not recommended and should be avoided within 2 weeks of initiating ketoconazole, unless the potential benefits outweigh potential risks. Concomitant use may cause decreased ketoconazole plasma concentrations resulting in decreased ketoconazole efficacy. Consider alternative antifungal treatment in a patient receiving efavirenz, as no recommendations for dose adjustments of ketoconazole are available. Also consider alternatives to efavirenz in a patient already taking another drug that prolongs the QT interval, such as ketoconazole, as additive effects on the QT interval may occur . If concomitant use is required, monitor antifungal response as ketoconazole dosage adjustments may be necessary .
Mechanism Of Interaction
Induction of CYP3A4-mediated ketoconazole metabolism by efavirenz; additive effects on QT interval
Literature Reports
A) In a two-phase pharmacokinetic interaction study (n=12), coadministration of efavirenz and ketoconazole led to significantly decreased ketoconazole exposure and maximum plasma concentrations. In phase one, HIV-positive treatment-naive adults (mean age, 33.7 years) received ketoconazole 400 mg as a single oral dose on day 1. In phase two, patients received 600 mg of efavirenz once daily in combination with 150 mg of lamivudine and 30 or 40 mg of stavudine twice daily on days 2 to 16. On day 16, ketoconazole 400 mg was given as a single oral dose and the pharmacokinetics of ketoconazole were studied on days 1 and 16. Pretreatment with efavirenz significantly decreased the clearance of ketoconazole by 201% (p less than 0.05). Compared to phase 1, the mean Cmax, AUC(0-24), and elimination half-life of ketoconazole decreased by 44% (p less than 0.01), 72% (p less than 0.01), and 58% (p less than 0.05), respectively. Although the mean Cmin and Vd were decreased by 96% and 33%, respectively, compared to phase one, the differences were not statistically significant. The Tmax was not significantly increased in phase two when compared to phase one, indicating that efavirenz did not affect the rate of ketoconazole absorption. The postulated mechanism of the pharmacokinetic interaction between ketoconazole and efavirenz was induction of CYP3A4-mediated ketoconazole metabolism by efavirenz .
Ketoconazole Overview
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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.
Efavirenz Overview
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Efavirenz is used along with other medications to treat human immunodeficiency virus (HIV) infection. Efavirenz is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It works by decreasing the amount of HIV in the blood. Although efavirenz does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.
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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.