Crizotinib with Itraconazole Interaction Details
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Brand Names Associated with Itraconazole
- Itraconazole
- Onmel®
- Sporanox®
- Tolsura®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased crizotinib exposure; increased itraconazole exposure and an increased risk of QT interval prolongation
Interaction Summary
The concomitant use of crizotinib with itraconazole may cause increased crizotinib plasma concentrations and should be avoided during and for 2 weeks after itraconazole therapy. Additionally, concurrent use of crizotinib, a CYP3A4 inhibitor, with a drug that is predominantly metabolized by CYP3A4, such as itraconazole, may result in increased itraconazole exposure . Both drugs are also known to increase the QT interval . If concomitant use cannot be avoided, monitor ECG and electrolytes and dosage reductions of crizotinib are required. In patients with non-small cell lung cancer, decrease the dose of crizotinib to 250 mg orally once daily. In patients with anaplastic large cell lymphoma, and body surface area (BSA) 1.7 m(2) or greater, reduce crizotinib to 250 mg twice daily; BSA 1.17 to 1.69 m(2), reduce to 200 mg twice daily; BSA 0.81 to 1.16 m(2), reduce to 250 mg once daily; BSA 0.6 to 0.8 m(2), permanently discontinue. Once itraconazole is discontinued, resume the prior dose of crizotinib .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
The concomitant use of crizotinib with itraconazole may cause increased crizotinib plasma concentrations and should be avoided during and for 2 weeks after itraconazole therapy. Additionally, concurrent use of crizotinib, a CYP3A4 inhibitor, with a drug that is predominantly metabolized by CYP3A4, such as itraconazole, may result in increased itraconazole exposure . Both drugs are also known to increase the QT interval . If concomitant use cannot be avoided, monitor ECG and electrolytes and dosage reductions of crizotinib are required. In patients with non-small cell lung cancer, decrease the dose of crizotinib to 250 mg orally once daily. In patients with anaplastic large cell lymphoma, and body surface area (BSA) 1.7 m(2) or greater, reduce crizotinib to 250 mg twice daily; BSA 1.17 to 1.69 m(2), reduce to 200 mg twice daily; BSA 0.81 to 1.16 m(2), reduce to 250 mg once daily; BSA 0.6 to 0.8 m(2), permanently discontinue. Once itraconazole is discontinued, resume the prior dose of crizotinib .
Mechanism Of Interaction
Inhibition of CYP3A-mediated crizotinib metabolism by itraconazole; inhibition of CYP3A-mediated itraconazole metabolism by crizotinib; additive QT interval prolongation
Literature Reports
A) In a pharmacokinetic study, coadministration of crizotinib 250 mg twice daily for 28 days (CYP3A inhibitor) with oral midazolam (CYP3A substrate) resulted in a 3.7-fold increase in the geometric mean midazolam AUC compared with midazolam administered alone. This clinical study with a CYP3A4 substrate suggests that crizotinib is a moderate inhibitor or CYP3A4 .
B) Coadministration of ketoconazole 200 mg twice daily, a strong CYP3A inhibitor, with a single 150 mg dose of crizotinib (CYP3A substrate) increased the AUC and Cmax of crizotinib by 216% and 44%, respectively .
C) Coadministration of itraconazole 200 mg once daily, a strong CYP3A inhibitor, with crizotinib 250 mg once daily (CYP3A substrate) increased the steady-state AUC and Cmax of crizotinib by 57% and 33%, respectively .
Crizotinib Overview
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Crizotinib is used to treat certain types of non-small cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body. It is also used to treat a certain type of anaplastic large cell lymphoma (ALCL) that has returned or is unresponsive to other treatment(s) in certain adults and children 1 year of age and older. Crizotinib is also used to treat a certain type of inflammatory myofibroblastic tumor (IMT; type of cancer that occurs in mucosal tissues usually in the abdominal area, involving the lungs, bladder, stomach, uterus, liver, or intestines) that cannot be treated with surgery or that has not improved or has come back after previous treatment(s) in adults and children 1 year of age and older. Crizotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
Itraconazole Overview
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Itraconazole capsules (Sporanox, Tolsura) are used to treat fungal infections in the lungs that can spread throughout the body. Itraconazole capsules (Sporanox) are also used to treat fungal infections of the fingernails and toenails. Itraconazole oral solution (liquid) is used to treat yeast infections of the mouth and throat or of the esophagus (tube that connects the throat to the stomach). Itraconazole is in a class of antifungals called triazoles. 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.