Lorlatinib with Conivaptan Interaction Details
Brand Names Associated with Lorlatinib
- Lorbrena®
- Lorlatinib
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 28, 2023
Interaction Effect
Increased lorlatinib exposure and increased incidence and severity of adverse reactions; decreased CYP3A substrate exposure
Interaction Summary
Concomitant use of lorlatinib (a CYP3A substrate and CYP3A inducer) with a strong CYP3A inhibitor/sensitive CYP3A substrate increases lorlatinib exposure and decreases the exposure of the CYP3A substrate. This may increase the incidence and severity of adverse reactions associated with lorlatinib and may reduce the efficacy of sensitive CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures. Avoid the concomitant use of lorlatinib with a strong CYP3A inhibitor/sensitive CYP3A substrates. 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. Also increasing the strong CYP3A inhibitor/sensitive CYP3A substrate dosage may be needed.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of lorlatinib (a CYP3A substrate and CYP3A inducer) with a strong CYP3A inhibitor/sensitive CYP3A substrate increases lorlatinib exposure and decreases the exposure of the CYP3A substrate. This may increase the incidence and severity of adverse reactions associated with lorlatinib and may reduce the efficacy of sensitive CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures. Avoid the concomitant use of lorlatinib with a strong CYP3A inhibitor/sensitive CYP3A substrates. 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. Also increasing the strong CYP3A inhibitor/sensitive CYP3A substrate dosage may be needed.
Mechanism Of Interaction
Inhibition of CYP3A-mediated lorlatinib metabolism; induction of CYP3A substrate metabolism
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% .
B) Coadministration of lorlatinib 150 mg orally once daily for 15 days with a single oral dose of midazolam 2 mg (a sensitive CYP3A substrate) decreased the midazolam AUC(infinity) by 64% and Cmax by 50% .
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.