Crizotinib with Velpatasvir Interaction Details
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased velpatasvir exposure; increased crizotinib exposure; increased risk of QT-interval prolongation or bradycardia
Interaction Summary
The concomitant use of crizotinib (CYP3A/P-gp inhibitor and CYP3A substrate) with velpatasvir (P-gp inhibitor and CYP3A/P-gp substrate) may cause increased exposure of crizotinib and/or velpatasvir. Consider reducing crizotinib dose and monitoring therapeutic drug concentrations. May consider alternative symptomatic treatment, sofosbuvir/velpatasvir treatment substitution, or antitumor treatment substitution. Monitor heart rate regularly and avoid combination with other bradycardiac agents.
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
The concomitant use of crizotinib (CYP3A/P-gp inhibitor and CYP3A substrate) with velpatasvir (P-gp inhibitor and CYP3A/P-gp substrate) may cause increased exposure of crizotinib and/or velpatasvir. Consider reducing crizotinib dose and monitoring therapeutic drug concentrations. May consider alternative symptomatic treatment, sofosbuvir/velpatasvir treatment substitution, or antitumor treatment substitution. Monitor heart rate regularly and avoid combination with other bradycardiac agents.
Mechanism Of Interaction
Inhibition of P-glycoprotein-mediated velpatasvir metabolism by crizotinib; inhibition of P-glycoprotein-mediated crizotinib metabolism by velpatasvir
Literature Reports
A) A 75-year-old man with no previous cardiac history was diagnosed with metastatic, synchronous non-small cell lung cancer. Crizotinib 250 mg twice daily was initiated, and 2 months later, sofosbuvir/velpatasvir (400 mg/100 mg once daily) was initiated for chronic hepatitis C virus (HCV) infection. One week after sofosbuvir/velpatasvir initiation, the patient experienced lower limb edema and class III New York Heart Association dyspnea. Grade 2 sinus bradycardia was revealed with normal PR interval and crizotinib therapy was discontinued. A 1.6-fold increase in crizotinib plasma trough concentration had occurred since sofosbuvir/velpatasvir initiation. Symptoms resolved, then crizotinib was resumed at 200 mg twice daily and was well tolerated. Velpatasvir plasma drug monitoring was performed at 1 and 2 months after crizotinib reinitiation revealing velpatasvir plasma overexposure, with trough concentrations of 1255 and 1752 nanogram (ng)/mL, respectively (mean target, 42 +/- 28 ng/mL). Sofosbuvir/velpatasvir was discontinued and 1 month later crizotinib was increased to 250 mg twice daily without toxicity .
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.
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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.