Clarithromycin with Lorlatinib Interaction Details
Brand Names Associated with Clarithromycin
- Biaxin® Filmtab®
- Biaxin® Granules
- Biaxin® XL Filmtab
- Biaxin® XL Pac
- Clarithromycin
Brand Names Associated with Lorlatinib
- Lorbrena®
- Lorlatinib
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 28, 2023
Interaction Effect
Reduced clarithromycin exposure and potential loss of efficacy, increased exposure of lorlatinib and risk for toxicity
Interaction Summary
Avoid concomitant use of clarithromycin (a strong CYP3A4 inhibitor and a CYP3A4 substrate) with lorlatinib (a CYP3A4 substrate and a moderate CYP3A4 inducer). Concomitant use may reduce the clarithromycin plasma concentrations which may reduce the effectiveness of clarithromycin and may also increase the plasma concentrations of lorlatinib and the risk of adverse reactions. If concomitant use cannot be avoided, reduce the starting dose of lorlatinib to 75 mg orally once daily. In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a strong CYP3A inhibitor, reduce the lorlatinib dose to 50 mg orally once daily. If concomitant use of a strong CYP3A inhibitor is discontinued, increase the lorlatinib dose (after 3 plasma half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of clarithromycin (a strong CYP3A4 inhibitor and a CYP3A4 substrate) with lorlatinib (a CYP3A4 substrate and a moderate CYP3A4 inducer). Concomitant use may reduce the clarithromycin plasma concentrations which may reduce the effectiveness of clarithromycin and may also increase the plasma concentrations of lorlatinib and the risk of adverse reactions. If concomitant use cannot be avoided, reduce the starting dose of lorlatinib to 75 mg orally once daily. In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a strong CYP3A inhibitor, reduce the lorlatinib dose to 50 mg orally once daily. If concomitant use of a strong CYP3A inhibitor is discontinued, increase the lorlatinib dose (after 3 plasma half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor .
Mechanism Of Interaction
Induction of CYP3A-mediated metabolism of clarithromycin; inhibition of CYP3A4-substrate metabolism by clarithromycin
Literature Reports
A) Coadministration of a single 100-mg dose of lorlatinib with itraconazole (a strong CYP3A inhibitor) resulted in an increase in lorlatinib AUC(infinity) by 42% and Cmax by 24% .
Clarithromycin Overview
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Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.
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Antibiotics such as clarithromycin 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.
Lorlatinib Overview
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Lorlatinib 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. Lorlatinib 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:
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.