Dasatinib with Ketoconazole Interaction Details
Brand Names Associated with Dasatinib
- Dasatinib
- Sprycel®
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 31, 2023
Interaction Effect
Increased dasatinib plasma concentrations and increased risk of QT interval prolongation
Interaction Summary
Concomitant use of dasatinib, a CYP3A4 substrate, and ketoconazole, a strong CYP3A4 inhibitor, resulted in significant increases in dasatinib exposure. Additionally, both drugs are capable of independently prolonging the QT interval. Concomitant use of dasatinib and ketoconazole should be avoided. However, if ketoconazole must be administered with dasatinib, then consider reducing the dasatinib dose to 20 mg daily for patients taking dasatinib 100 mg daily or to 40 mg daily for patients taking dasatinib 140 mg daily. Monitor patients closely for toxicity. If dasatinib is not tolerated following a dose reduction, then ketoconazole must be discontinued or dasatinib must be discontinued until ketoconazole treatment is stopped. Once therapy with ketoconazole is discontinued, a washout period of approximately 1 week should be allowed before increasing the dasatinib to the indicated dose . If concomitant use is required, consider a baseline ECG and on-treatment monitoring.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of dasatinib, a CYP3A4 substrate, with strong CYP3A4 inhibitors, such as ketoconazole, due to the potential for increased dasatinib exposure. Additionally, both drugs are capable of independently prolonging the QT interval. If ketoconazole must be administered with dasatinib, consider reducing the dasatinib dose to 20 mg daily for patients taking dasatinib 100 mg daily or to 40 mg daily for patients taking dasatinib 140 mg daily. Monitor patients closely for toxicity. If dasatinib is not tolerated following a dose reduction, then either discontinue ketoconazole or discontinue dasatinib until ketoconazole treatment is stopped. Once therapy with ketoconazole is discontinued, allow a washout period of approximately 1 week before increasing the dasatinib to the indicated dose . If concomitant use is required, consider a baseline ECG and on-treatment monitoring.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated dasatinib metabolism; additive QT-interval prolongation
Literature Reports
A) An interaction between dasatinib and ketoconazole, a strong CYP3A4 inhibitor, resulted in increased dasatinib plasma concentrations and exposure. Dasatinib Cmax and AUC were increased by 4-fold and 5-fold, respectively, following coadministration of dasatinib 20 mg daily with ketoconazole 200 mg twice daily to patients with solid tumors (n=18) .
Dasatinib Overview
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Dasatinib is used to treat a certain type of chronic myeloid leukemia (CML; a type of cancer of the white blood cells) as a first treatment and in adults who can no longer benefit from other leukemia medications including imatinib (Gleevec) or in those who cannot take these medications because of side effects. Dasatinib is also used to treat a certain type of chronic CML in children 1 year of age or older. Dasatinib is also used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer of the white blood cells) in adults who can no longer benefit from other leukemia medications or who cannot take these medications because of side effects. It is also used in combination with chemotherapy medications to treat a certain type of ALL in children 1 year of age or older.Dasatinib 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 stop the spread of cancer cells.
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.
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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.