Atazanavir with Entrectinib Interaction Details

Brand Names Associated with Atazanavir

Brand Names Associated with Entrectinib

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 29, 2024

Interaction Effect

Increased entrectinib exposure, an increased frequency or severity of adverse reactions including increased risk of cardiac arrhythmias and an increased risk of QT interval prolongation

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 2 years or older, reduce the 600 mg or 400 mg starting entrectinib dose to 200 mg orally once daily, 300 mg to 100 mg, 200 mg to 50 mg once daily and limit coadministration to 14 days or less. 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. For pediatric patients with a starting dose less than 200 mg avoid coadministration with moderate CYP3A inhibitors. Also, assess QT interval and electrolytes prior to initiation of entrectinib and periodically during treatment. Based on the severity of QTc interval prolongation, withhold entrectinib and then resume at same or reduced dose, or permanently discontinue[1].

Severity

Major

Onset

Unspecified

Evidence

Probable

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 2 years or older, reduce the 600 mg or 400 mg starting entrectinib dose to 200 mg orally once daily, 300 mg to 100 mg, 200 mg to 50 mg once daily and limit coadministration to 14 days or less. 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. For pediatric patients with a starting dose less than 200 mg avoid coadministration with moderate CYP3A inhibitors. Also, assess QT interval and electrolytes prior to initiation of entrectinib and periodically during treatment. Based on the severity of QTc interval prolongation, withhold entrectinib and then resume at same or reduced dose, or permanently discontinue[1].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of entrectinib; 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 [1].

References

1 ) Product Information: ROZLYTREK(R) oral capsules, pellets, entrectinib oral capsules, pellets. Genentech Inc (per FDA), South San Francisco, CA, 2023.

Atazanavir Overview

• Atazanavir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months of age and weigh at least 22 lb (10 kg). Atazanavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Atazanavir must be given with other medications that treat HIV infection to completely treat the infection. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

Entrectinib Overview

• 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:

• 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.