Larotrectinib with Fluconazole Interaction Details
Brand Names Associated with Larotrectinib
- Larotrectinib
- VitrakviI®
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased larotrectinib exposure and increase in the incidence or severity of adverse reactions
Interaction Summary
Monitor for adverse reactions more frequently in patients coadministered with larotrectinib and a moderate CYP3A4 inhibitor, and reduce the larotrectinib dosage based on the severity of emergent adverse reactions. Concomitant use of larotrectinib with a moderate CYP3A4 inhibitor may increase larotrectinib plasma concentrations, which may result in a higher incidence of adverse reactions. For Grade 3 or 4 adverse reactions, withhold larotrectinib until adverse reaction resolves or improves to baseline or Grade 1. If resolution occurs within 4 weeks, resume at the next dosage modification (first dosage modification, 75 mg orally twice daily; second dosage modification, 50 mg twice daily; third dosage modification, 100 mg once daily). Permanently discontinue larotrectinib if an adverse reaction does not resolve within 4 weeks and in patients who are unable to tolerate larotrectinib after 3 dose modifications. Coadministration of larotrectinib with fluconazole (a moderate CYP3A4 inhibitor) is predicted to increase larotrectinib steady state AUC by 2.7-fold and Cmax by 1.9-fold.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Monitor for adverse reactions more frequently in patients coadministered with larotrectinib and a moderate CYP3A4 inhibitor, and reduce the larotrectinib dosage based on the severity of emergent adverse reactions. Concomitant use of larotrectinib with a moderate CYP3A4 inhibitor may increase larotrectinib plasma concentrations, which may result in a higher incidence of adverse reactions. For Grade 3 or 4 adverse reactions, withhold larotrectinib until adverse reaction resolves or improves to baseline or Grade 1. If resolution occurs within 4 weeks, resume at the next dosage modification (first dosage modification, 75 mg orally twice daily; second dosage modification, 50 mg twice daily; third dosage modification, 100 mg once daily). Permanently discontinue larotrectinib if an adverse reaction does not resolve within 4 weeks and in patients who are unable to tolerate larotrectinib after 3 dose modifications.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of larotrectinib
Literature Reports
A) Coadministration of larotrectinib with fluconazole (a moderate CYP3A4 inhibitor) is predicted to increase larotrectinib steady state AUC by 2.7-fold and Cmax by 1.9-fold .
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.
Fluconazole Overview
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Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. 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.