Venetoclax with Larotrectinib Interaction Details
Brand Names Associated with Venetoclax
- Venclexta®
- Venetoclax
Brand Names Associated with Larotrectinib
- Larotrectinib
- VitrakviI®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased sensitive CYP3A4 substrate exposure and increase in the incidence or severity of adverse reactions
Interaction Summary
Coadministration of larotrectinib (a CYP3A4 inhibitor) with a sensitive CYP3A4 substrate should be avoided. If concomitant use cannot be avoided, monitor for increased adverse reactions of the sensitive substrate. Concomitant use of larotrectinib (a CYP3A4 inhibitor) with a sensitive CYP3A4 substrate may increase plasma concentrations of the sensitive CYP3A4 substrate, which may increase the incidence or severity of adverse reactions. Coadministration of larotrectinib 100 mg twice daily with midazolam, a sensitive CYP3A4 substrate, increased both the AUC(0 to infinity) and Cmax of midazolam by 1.7-fold compared with midazolam administered alone.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Coadministration of larotrectinib (a CYP3A4 inhibitor) with a sensitive CYP3A4 substrate should be avoided. Concomitant use of larotrectinib (a CYP3A4 inhibitor) with a sensitive CYP3A4 substrate may increase plasma concentrations of the sensitive CYP3A4 substrate, which may increase the incidence or severity of adverse reactions. If concomitant use cannot be avoided, monitor for increased adverse reactions of the sensitive substrate.
Mechanism Of Interaction
Inhibition of CYP3A4 substrate metabolism by larotrectinib
Literature Reports
A) Coadministration of larotrectinib 100 mg twice daily with midazolam, a sensitive CYP3A4 substrate, increased both the AUC(0 to infinity) and Cmax of midazolam by 1.7-fold compared with midazolam administered alone. The AUC(0 to infinity) and Cmax of 1-hydroxymidazolam, the main metabolite of midazolam, were both increased 1.4-fold .
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.
Larotrectinib Overview
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Larotrectinib is used to treat a certain type of solid tumors in adults, children, and infants 4 weeks of age and older that have spread to other parts of the body or cannot be treated successfully with surgery. This medication is used only if there are no other treatments available and the tumors have worsened after receiving other treatments. Larotrectinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that tells the cancer cells to multiply. This may help slow the growth of tumors.
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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.