Mitotane with Selumetinib Interaction Details
Brand Names Associated with Mitotane
- Lysodren®
- Mitotane
Brand Names Associated with Selumetinib
- Koselugo®
- Selumetinib
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 29, 2023
Interaction Effect
Decreased selumetinib exposure
Interaction Summary
Selumetinib and its active N-desmethyl metabolite are primarily metabolized by CYP3A4. In a pharmacokinetic trial, the concomitant use of rifampin (strong CYP3A4 inducer) decreased selumetinib AUC by 51% and Cmax by 26%. Coadministration with efavirenz (moderate CYP3A4 inducer) is predicted through modeling to reduce selumetinib AUC by 38% and Cmax by 22%. Avoid concomitant use of selumetinib with a strong or moderate CYP3A4 inducer as reduced selumetinib exposure may result in reduced efficacy.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of selumetinib (a CYP3A4 substrate) with a strong or moderate CYP3A4 inducer as reduced selumetinib efficacy could occur.
Mechanism Of Interaction
Induction of CYP3A4-mediated selumetinib metabolism
Literature Reports
A) Concomitant use of rifampicin (strong CYP3A4 inducer) decreased selumetinib AUC by 51% and Cmax by 26% in a clinical study. Coadministration with efavirenz (moderate CYP3A4 inducer) is predicted to reduce selumetinib AUC by 38% and Cmax by 22% .
Mitotane Overview
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Mitotane is used to treat cancer of the adrenal gland that can not be treated with surgery. Mitotane is in a class of medications called antineoplastic agents. It works by slowing growth or reducing the size of the tumor.
Selumetinib Overview
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Selumetinib is used to treat neurofibromatosis type 1 (NF1; a nervous system disorder that causes tumors to grow on nerves) in children 2 years of age and older who have plexiform neurofibromas (PN; soft tumors) that cannot be completely removed by surgery. Selumetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals the tumors to grow. This helps to stop or slow tumor growth.
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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.