Crizotinib with Erythromycin Interaction Details

Brand Names Associated with Crizotinib

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 20, 2023

Interaction Effect

Increased crizotinib exposure; increased erythromycin exposure; increased risk of QT-interval prolongation

Interaction Summary

Both crizotinib and erythromycin are moderate CYP3A4 inhibitors and CYP3A4 substrates associated with QT-interval prolongation. Although this specific interaction has not been evaluated, the concomitant use of crizotinib with erythromycin may increase plasma concentrations of crizotinib, erythromycin, or both and increase the risk for QT prolongation and other serious cardiac adverse events, including torsade de pointes . If coadministration is required, use caution and consider periodic ECG and electrolyte monitoring. Dose reduction of erythromycin  or crizotinib may also be warranted.

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Both crizotinib and erythromycin are known to increase the QT interval and concurrent use of these agents may increase the risk of cardiac adverse events. Additionally, crizotinib and erythromycin are both CYP3A4 inhibitors and substrates with the potential to increase plasma concentrations of each other. If crizotinib is coadministered with erythromycin, use caution and consider periodic ECG and electrolyte monitoring. Dose reduction of erythromycin  and crizotinib may also be warranted.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated crizotinib metabolism by erythromycin; inhibition of CYP3A4-mediated erythromycin metabolism by crizotinib; additive effects on QT interval

Literature Reports

A) Crizotinib systemic exposure rose significantly when coadministered with ketoconazole, a strong CYP3A4 inhibitor. Patients treated with ketoconazole 200 mg twice daily administered a single dose of crizotinib 150 mg experienced approximately 3.2-fold and 1.4-fold increases in crizotinib AUC and Cmax, respectively, compared with AUC and Cmax values following crizotinib monotherapy. However, the impact of CYP3A4 inhibitors on steady-state crizotinib exposure is unknown .

B) 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 mean midazolam AUC compared with midazolam administered alone This clinical study with a CYP3A4 substrate suggests that crizotinib is a moderate inhibitor of CYP3A4 .

Crizotinib Overview

• 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.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.