Encorafenib with Erythromycin Interaction Details

Brand Names Associated with Encorafenib

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 22, 2023

Interaction Effect

Increased encorafenib exposure and prolongation of QTc interval

Interaction Summary

Concomitant administration of encorafenib with a moderate CYP3A4 inhibitor that prolongs the QTc interval increased encorafenib plasma concentrations and may increase encorafenib adverse reactions, including additive QTc prolongation. Coadministration of diltiazem (a moderate CYP3A4 inhibitor) with encorafenib increased the AUC and Cmax of encorafenib. Coadministration should be avoided. If coadministration cannot be avoided, reduce the encorafenib dose. If the current encorafenib dose is 450 mg/day, reduce to 225 mg/day, if the current dose is 300 mg/day, reduce to 150 mg/day, and if the current dose is 225 or 150 mg/day, reduce to 75 mg/day. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the encorafenib dose that was taken prior to initiating the CYP3A4 inhibitor. Monitor patients for QTc prolongation.

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant administration of encorafenib with a moderate CYP3A4 inhibitor that prolongs the QTc interval increased encorafenib plasma concentrations and may increase encorafenib adverse reactions, including additive QTc prolongation. Coadministration should be avoided. If coadministration cannot be avoided, reduce the encorafenib dose. If the current encorafenib dose is 450 mg/day, reduce to 225 mg/day, if the current dose is 300 mg/day, reduce to 150 mg/day, and if the current dose is 225 or 150 mg/day, reduce to 75 mg/day. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the encorafenib dose that was taken prior to initiating the CYP3A4 inhibitor. Monitor patients for QTc prolongation.

Mechanism Of Interaction

Inhibition of CYP3A-mediated encorafenib metabolism; additive prolongation on QTc interval

Literature Reports

A) Coadministration of diltiazem (a moderate CYP3A4 inhibitor) with encorafenib increased the AUC of encorafenib by 2-fold and increased the Cmax by 45% following a single dose of encorafenib 50 mg (0.1 times the usual dose) .

Encorafenib Overview

• Encorafenib is used along with binimetinib (Mektovi) to treat certain types of melanoma (a type of skin cancer) that has spread to other parts of the body or cannot be removed by surgery. It is also used with cetuximab (Erbitux) to treat a certain type of colon cancer in adults that has spread to other parts of the body after other treatment(s). Encorafenib 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.

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.