Lorlatinib with Posaconazole Interaction Details
Brand Names Associated with Lorlatinib
- Lorbrena®
- Lorlatinib
Brand Names Associated with Posaconazole
- Noxafil PowderMix®
- Noxafil®
- Posaconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 28, 2023
Interaction Effect
Increased lorlatinib exposure and an increased incidence and severity of adverse reactions
Interaction Summary
Concomitant use of lorlatinib (a CYP3A substrate) with a strong CYP3A inhibitor may lead to an increase in lorlatinib exposure, which may increase the incidence and severity of adverse reactions of lorlatinib. Lorlatinib AUC and Cmax was increased by 42% and 24%, respectively, with concomitant itraconazole (strong CYP3A inhibitor). Avoid the concomitant use of lorlatinib with a strong CYP3A inhibitor. 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
Concomitant use of lorlatinib (a CYP3A substrate) with a strong CYP3A inhibitor may lead to an increase in lorlatinib exposure, which may increase the incidence and severity of adverse reactions of lorlatinib. Avoid the concomitant use of lorlatinib with a strong CYP3A inhibitor. 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
Inhibition of CYP3A-mediated lorlatinib 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% .
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.
Posaconazole Overview
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Posaconazole is used to prevent serious fungal infections that can spread throughout the body in adults and children 2 years of age and older with a weakened ability to fight infection. Posaconazole delayed-release tablets are used to treat invasive aspergillosis (a serious fungal infection that begins in the lungs and spreads through the bloodstream to other organs) in adults and teenagers 13 years of age and older. Posaconazole oral suspension is also used to treat yeast infections of the mouth and throat including yeast infections in adults and teenagers 13 years of age and older that could not be treated successfully with other medications. Posaconazole is in a class of medications called azole antifungals. It works by slowing the growth of fungi that cause infection.
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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.