Crizotinib with Ranolazine Interaction Details
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Brand Names Associated with Ranolazine
- Ranexa®
- Ranolazine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased ranolazine exposure; increased risk of QT-interval prolongation
Interaction Summary
Crizotinib is a moderate CYP3A4 inhibitor, ranolazine is a CYP3A4 substrate, and both are known to increase the QT interval. Although this interaction has not been evaluated, concurrent use of crizotinib with ranolazine may increase ranolazine exposure and the risk of prolonged QT interval and serious cardiac adverse events, including torsade de pointes. If coadministration is required, use caution, do not exceed ranolazine doses of 500 mg twice daily , and consider periodic monitoring of ECG and electrolytes . Dose reduction of crizotinib may also be warranted.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Coadministration of crizotinib with ranolazine may increase ranolazine plasma concentrations. Additionally, both crizotinib and ranolazine are known to increase the QT interval and concurrent use of these agents may increase the risk of cardiac adverse events and should therefore be undertaken with caution. If coadministration is required, do not exceed ranolazine doses of 500 mg twice daily and consider periodic monitoring of ECG and electrolytes . Dose reduction of crizotinib may also be warranted.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated ranolazine metabolism by crizotinib; additive effects on QT interval
Literature Reports
A) In a pharmacokinetic study, coadministration of crizotinib (250 mg twice daily for 28 days) with oral midazolam 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 of CYP3A4 .
B) In a pharmacokinetic study, coadministration of ranolazine 1000 mg twice daily with diltiazem 180 to 360 mg daily (a moderate CYP3A4 inhibitor) increased ranolazine plasma concentrations by 50% to 130% compared with ranolazine administered alone .
C) In a pharmacokinetic study, coadministration of ranolazine 750 mg twice daily with verapamil 120 mg 3 times daily (a moderate CYP3A4 inhibitor) increased ranolazine plasma concentrations by 100% compared with ranolazine administered alone .
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.
Ranolazine Overview
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Ranolazine is used alone or with other medications to treat chronic angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen). Ranolazine is in a class of medications called anti-anginals. The exact way that ranolazine works is not known at this time.
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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.