Venetoclax with Lorlatinib Interaction Details
Brand Names Associated with Venetoclax
- Venclexta®
- Venetoclax
Brand Names Associated with Lorlatinib
- Lorbrena®
- Lorlatinib
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 28, 2023
Interaction Effect
Decreased exposure of the CYP3A substrate
Interaction Summary
Concomitant use of lorlatinib (a CYP3A inducer) decreases the concentration of CYP3A substrates, which may reduce the efficacy of these substrates. Avoid concomitant use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures. When lorlatinib and midazolam (a sensitive CYP3A substrate) were coadministered, the midazolam AUC(infinity) decreased by 64%. If concomitant use is unavoidable, increasing the CYP3A substrate dosage may be needed.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of lorlatinib (a CYP3A inducer) decreases the concentration of CYP3A substrates, which may reduce the efficacy of these substrates. Avoid concomitant use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increasing the CYP3A substrate dosage may be needed.
Mechanism Of Interaction
Induction of CYP3A substrate metabolism by lorlatinib
Literature Reports
A) 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% .
Venetoclax Overview
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Venetoclax is used alone or in combination with obinutuzumab (Gazyva) or rituximab (Rituxan) to treat certain types of chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells) or certain types of small lymphocytic lymphoma (SLL; a type of cancer that begins mostly in the lymph nodes). It is also used in combination with either azacitidine (Vidaza), decitabine (Dacogen), or cytarabine as a first treatment for acute myeloid leukemia (AML; a type of cancer that begins in the white blood cells) in people 75 years of age or older, or in adults who have medical conditions that prevents them from being treated with other chemotherapy medications. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It works by blocking the action of a certain protein in the body that helps cancer cells survive. This helps to kill cancer cells.
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.