Selumetinib with Dronedarone Interaction Details
Brand Names Associated with Selumetinib
- Koselugo®
- Selumetinib
Brand Names Associated with Dronedarone
- Dronedarone
- Multaq®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 27, 2023
Interaction Effect
Increased selumetinib exposure and risk for adverse reactions
Interaction Summary
Selumetinib and its active N-desmethyl metabolite are primarily metabolized by CYP3A4, and to a lesser extent by CYP2C19. Avoid coadministration with a strong or moderate CYP3A4 inhibitor because increased selumetinib exposure and risk for toxicity may occur. In pharmacokinetic trials, concomitant use of itraconazole (strong CYP3A4 inhibitor) and fluconazole (strong CYP2C19 inhibitor and moderate CYP3A4 inhibitor) increased selumetinib AUC and Cmax. Coadministration with erythromycin (moderate CYP3A4 inhibitor) is predicted through modeling to increase selumetinib AUC and Cmax. If coadministration is required, reduce current selumetinib dosage from 25 mg/m(2) twice daily to 20 mg/m(2) twice daily or from 20 mg/m(2) twice daily to 15 mg/m(2) twice daily. After discontinuation of the strong or moderate inhibitor for 3 elimination half-lives, resume the selumetinib dose that was taken prior to coadministration.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid coadministration of selumetinib with a strong or moderate CYP3A4 inhibitor, including fluconazole. If concomitant use of a strong or moderate inhibitor is required, reduce current selumetinib dosage from 25 mg/m(2) twice daily to 20 mg/m(2) twice daily or from 20 mg/m(2) twice daily to 15 mg/m(2) twice daily. After discontinuation of the strong or moderate inhibitor for 3 elimination half-lives, resume the selumetinib dose that was taken prior to coadministration.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of selumetinib
Literature Reports
A) Concomitant use of itraconazole (strong CYP3A4 inhibitor) increased selumetinib AUC by 49% and Cmax by 19% in a clinical study. Coadministration with erythromycin (moderate CYP3A4 inhibitor) is predicted to increase selumetinib AUC by 41% and Cmax by 23% .
B) Concomitant use of fluconazole (strong CYP2C19 and moderate CYP3A4 inhibitor) increased selumetinib AUC by 53% and Cmax by 26% in a clinical study .
Selumetinib Overview
-
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.
Dronedarone Overview
-
Dronedarone is used to treat people who currently have normal heart rhythm, but have had atrial fibrillation in the past. Dronedarone decreases the risk that people who have this condition will need to be hospitalized to treat atrial fibrillation. Dronedarone is in a class of medications called antiarrhythmics. It works by helping the heart to beat normally.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.