Pexidartinib with Ketoconazole Interaction Details
Brand Names Associated with Pexidartinib
- Pexidartinib
- Turalio®
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased pexidartinib exposure; hepatotoxicity
Interaction Summary
The concomitant use of pexidartinib (CYP3A4 substrate) with a strong CYP3A inhibitor may increase pexidartinib exposure and should be avoided. Pexidartinib coadministered with itraconazole (a strong CYP3A inhibitor) resulted in a 70% increase in mean pexidartinib AUC and a 48% increase in pexidartinib Cmax. If coadministration is required, reduce pexidartinib dose based on planned total daily dose: from 800 or 600 mg/day to 200 mg twice daily; from 400 mg/day to 200 mg once daily. If the CYP3A inhibitor is discontinued, return to previous pexidartinib dose after 3 plasma half-lives of the CYP3A inhibitor have passed. Additionally, pexidartinib can cause serious and potentially fatal liver injury; hepatotoxicity with ductopenia and cholestasis occurred during clinical trials with pexidartinib. The mechanism is unknown and occurrence is not predictable. Avoid coadministration with other drugs known to cause hepatotoxicity in patients with increased (greater than ULN) serum transaminases, total bilirubin, or direct bilirubin or active liver or biliary tract disease.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
The concomitant use of pexidartinib (CYP3A4 substrate) with a strong CYP3A inhibitor may increase pexidartinib exposure and should be avoided. If coadministration is required, reduce pexidartinib dose based on planned total daily dose: from 800 or 600 mg/day to 200 mg twice daily; from 400 mg/day to 200 mg once daily. If the CYP3A inhibitor is discontinued, return to previous pexidartinib dose after 3 plasma half-lives of the CYP3A inhibitor have passed. Additionally, pexidartinib can cause serious and potentially fatal liver injury; hepatotoxicity with ductopenia and cholestasis occurred during clinical trials with pexidartinib. The mechanism is unknown and occurrence is not predictable. Avoid coadministration with other drugs known to cause hepatotoxicity in patients with increased (greater than ULN) serum transaminases, total bilirubin, or direct bilirubin or active liver or biliary tract disease.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of pexidartinib; additive risk for hepatotoxicity
Literature Reports
A) Pexidartinib coadministered with itraconazole (another strong CYP3A inhibitor) resulted in a 70% increase in mean pexidartinib AUC and a 48% increase in pexidartinib Cmax .
Pexidartinib Overview
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Pexidartinib is used to treat tenosynovial giant cell tumors (TGCT; tumors in or around a joint that can cause pain, swelling, and reduce movement) in adults that cannot be treated by surgery. Pexidartinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that may help the tumor to shrink.
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.