Ketoconazole with Eliglustat Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Eliglustat
- Cerdelga®
- Eliglustat
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased eliglustat exposure and subsequent prolongation of the QT interval
Interaction Summary
Concomitant use of eliglustat and ketoconazole (a strong CYP3A inhibitor) increased eliglustat AUC 4.4-fold to 6.2-fold, while concomitant use with both ketoconazole and paroxetine (a strong CYP2D6 inhibitor) increased eliglustat AUC 9.8-fold to 24.2-fold. In extensive CYP2D6 metabolizers, reduce the eliglustat dosage to 84 mg once daily if used concomitantly with a strong CYP3A inhibitor. In extensive CYP2D6 metabolizers, eliglustat use is contraindicated with the concomitant use of both a strong CYP3A inhibitor and strong or moderate CYP2D6 inhibitor. In intermediate and poor CYP2D6 metabolizers, concomitant use of eliglustat and strong CYP3A inhibitors is contraindicated.
Severity
Contraindicated
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
In extensive CYP2D6 metabolizers, reduce the eliglustat dose to 84 mg once daily if used concomitantly with a strong CYP3A inhibitor. In extensive CYP2D6 metabolizers, eliglustat use is contraindicated with the concomitant use of both a strong CYP3A inhibitor and strong or moderate CYP2D6 inhibitor. In intermediate and poor CYP2D6 metabolizers, concomitant use of eliglustat and strong CYP3A inhibitors is contraindicated.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated eliglustat metabolism
Literature Reports
A) Coadministration with the strong CYP3A inhibitor, ketoconazole, led to a 4-fold increase in eliglustat Cmax and a 4.4-fold increase in eliglustat AUC in extensive CYP2D6 metabolizers with Gaucher disease type 1. Among intermediate metabolizers, coadministration with ketoconazole was expected to increase eliglustat Cmax by 4.4-fold and AUC by 5.4-fold per pharmacokinetic modeling simulations. In poor metabolizers taking eliglustat 84 mg/day, concomitant use of ketoconazole was expected to increase eliglustat Cmax 4.3-fold and AUC 6.2-fold .
B) Among extensive CYP2D6 metabolizers with Gaucher disease type 1, simulations suggested that eliglustat Cmax would increase 16.7-fold and AUC would increase 24.2-fold with concomitant use of ketoconazole (a strong CYP3A inhibitor) plus paroxetine (a strong CYP2D6 inhibitor). Among intermediate metabolizers, the predicted eliglustat Cmax would increase 7.5-fold and AUC would increase 9.8-fold with concurrent use of ketoconazole plus paroxetine .
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.
Eliglustat Overview
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Eliglustat is used to treat Gaucher disease type 1 (a condition in which a certain fatty substance is not broken down normally in the body and builds up in some organs and causes liver, spleen, bone, and blood problems) in certain people. Eliglustat is in a class of medications called enzyme inhibitors. It works by preventing the body from producing the fatty substance so that less of it will build up in the body and cause symptoms.
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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.