Lorlatinib with Mavacamten Interaction Details
Brand Names Associated with Lorlatinib
- Lorbrena®
- Lorlatinib
Brand Names Associated with Mavacamten
- Camzyos®
- Mavacamten
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 28, 2023
Interaction Effect
Reduced mavacamten exposure, reduced efficacy of mavacamten, reduced CYP3A4 substrate exposure and reduced efficacy of CYP3A4 substrate
Interaction Summary
Concomitant use of mavacamten with a moderate CYP3A4 inducer that is also a CYP3A4 substrate is contraindicated, as it decreases mavacamten and/or substrates exposure, which may reduce the efficacy of mavacamten and/or CYP3A4 substrate. Closely monitor when mavacamten is used in combination with CYP3A4 substrates. Discontinuation of the inducer may increase the risk of heart failure due to systolic dysfunction.
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of mavacamten with a moderate CYP3A4 inducer that is also a CYP3A4 substrate is contraindicated, as it decreases mavacamten and/or substrates exposure, which may reduce the efficacy of mavacamten and/or the CYP3A4 substrate. Closely monitor when mavacamten is used in combination with CYP3A4 substrates. Discontinuation of the inducer may increase the risk of heart failure due to systolic dysfunction.
Mechanism Of Interaction
Induction of CYP3A4-mediated metabolism of mavacamten; induction of CYP3A4 substrate metabolism by mavacamten
Literature Reports
A) Concomitant use of mavacamten (a single 15 mg dose) with a strong CYP2C19 and CYP3A4 inducer (rifAMPin 600 mg daily dose) is predicted to decrease mavacamten AUC(0 to inf) and Cmax by 87% and 22%, respectively, in CYP2C19 normal metabolizers, and by 69% and 4%, respectively, in CYP2C19 poor metabolizers .
B) Concomitant use of a 16-day course of mavacamten (25 mg on days 1 and 2, followed by 15 mg for 14 days) resulted in a 13% and 7% decrease in midazolam AUC(inf) and Cmax, respectively, in healthy CYP2C19 normal metabolizers. Following coadministration of mavacamten once daily in hypertrophic cardiomyopathy patients, midazolam AUC(inf) and Cmax are predicted to decrease by 21% to 64% and 13% to 48%, respectively, depending on the dose of mavacamten and CYP2C19 phenotype .
Lorlatinib Overview
-
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.
Mavacamten Overview
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Mavacamten is used to treat adults with symptomatic obstructive hypertrophic cardiomyopathy. Mavacamten is in a class of medications called cardiac myosin inhibitors. It works by reducing the interaction between actin and myosin (proteins responsible for the contraction of the heart) so that the heart does not squeeze so hard.
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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.