Crizotinib with Entrectinib Interaction Details
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Brand Names Associated with Entrectinib
- Entrectinib
- Rozlytrek®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased entrectinib exposure and increased frequency or severity of adverse reactions including increased risk of cardiac arrhythmias
Interaction Summary
Avoid concomitant use of entrectinib (CYP3A substrate) with moderate CYP3A inhibitors that prolong the QT-interval since coadministration increases entrectinib plasma concentrations, which could increase the frequency or severity of adverse reactions, including risk of cardiac arrhythmias. Coadministration is predicted to increase entrectinib AUC (0 to Tau) by 3-fold and Cmax by 2.9-fold. If coadministration is unavoidable, in adults and pediatric patients 12 years or older with a BSA greater than 1.5 m(2), reduce the entrectinib dose to 200 mg orally once daily. After discontinuation of a moderate CYP3A inhibitor for 3 to 5 elimination half-lives, resume the entrectinib dose that was taken prior to initiating the CYP3A inhibitor.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of entrectinib (CYP3A substrate) with moderate CYP3A inhibitors that prolong the QT-interval since coadministration increases entrectinib plasma concentrations, which could increase the frequency or severity of adverse reactions, including risk of cardiac arrhythmias. If coadministration is unavoidable, in adults and pediatric patients 12 years or older with a body surface area (BSA) greater than 1.5 m(2), reduce the entrectinib dose to 200 mg orally once daily. After discontinuation of the moderate CYP3A inhibitor for 3 to 5 elimination half-lives, resume the entrectinib dose that was taken prior to initiating the CYP3A inhibitor.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of entrectinib and additive QT-interval prolongation
Literature Reports
A) Coadministration of a moderate CYP3A inhibitor with entrectinib is predicted to increase entrectinib AUC (0 to Tau) by 3-fold and Cmax by 2.9-fold .
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.
Entrectinib Overview
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Entrectinib is used to treat a certain type of non-small cell lung cancer (NSCLC) in adults that has spread to other parts of the body. It is also used to treat certain types of solid tumors in adults and children 12 years of age and older that cannot be treated by surgery or that has spread to other parts of the body and that worsened after treatment with other chemotherapy medications. Entrectinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps to stop or slow 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.