Ketoconazole with Erlotinib Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Erlotinib
- Erlotinib
- Tarceva®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 18, 2023
Interaction Effect
Increased erlotinib exposure and risk of toxicity
Interaction Summary
Concomitant use of erlotinib (a CYP3A4 substrate) with a strong CYP3A4 inhibitor may result in increased exposure of erlotinib increasing the risk for toxicity. During in-vitro drug-interaction studies, coadministration of erlotinib and strong CYP3A4 inhibitors resulted in a 2.1- to 4.2-fold increase in erlotinib AUC and prolonged the erlotinib half-life up to 16-fold . Avoid concurrent use, however if use is required, reduce the dose of erlotinib. If severe reactions occur with concomitant use, reduce the erlotinib dose in 50 mg decrements .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of erlotinib (a CYP3A4 substrate) with a strong CYP3A4 inhibitor may result in increased exposure of erlotinib and increased risk of toxicity. Avoid concurrent use, however if use is required, reduce the dose of erlotinib. If severe reactions occur with concomitant use, reduce the erlotinib dose in 50 mg decrements.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated erlotinib metabolism
Literature Reports
A) During drug interaction studies, coadministration of erlotinib and ketoconazole (a strong CYP3A4 inhibitor) resulted in a 67% increase in erlotinib AUC .
B) During in-vitro drug interaction studies, coadministration of erlotinib and ketoconazole (a strong CYP3A4 inhibitor) resulted in a 2.1-fold increase in erlotinib AUC and a moderate 1.9-fold increase in the half-life of erlotinib. Coadministration of erlotinib and ritonavir (a strong CYP3A4 inhibitor) resulted in a 4.2-fold increase in erlotinib AUC and a 16-fold increase in the half-life of erlotinib .
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.
Erlotinib Overview
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Erlotinib is used to treat certain types of non-small cell lung cancer that has spread to nearby tissues or to other parts of the body in patients who have already been treated with at least one other chemotherapy medication and have not gotten better. Erlotinib is also used in combination with another medication (gemcitabine [Gemzar]) to treat pancreatic cancer that has spread to nearby tissues or to other parts of the body and cannot be treated with surgery. Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.
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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.