Avapritinib with Trofinetide Interaction Details
Brand Names Associated with Avapritinib
- Avapritinib
- Ayvakit®
Brand Names Associated with Trofinetide
- Daybue®
- Trofinetide
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Mar 04, 2024
Interaction Effect
Increased CYP3A4 substrate exposure and an increased risk of CYP3A4 substrate-related toxicities
Interaction Summary
Concomitant administration of trofinetide with sensitive CYP3A4 substrates may increase the plasma concentrations of CYP3A4 substrates. Closely monitor when trofinetide is used in combination with orally administered CYP3A4 sensitive substrates for which a small change in substrate plasma concentration may lead to serious toxicities[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant administration of trofinetide with sensitive CYP3A4 substrates may increase the plasma concentrations of CYP3A4 substrates. Closely monitor when trofinetide is used in combination with orally administered CYP3A4 sensitive substrates for which a small change in substrate plasma concentration may lead to serious toxicities[1].
Mechanism Of Interaction
Inhibition of CYP3A4 substrate metabolism by trofinetide
Literature Reports
A) Trofinetide is a weak CYP3A4 inhibitor. Using physiologically based pharmacokinetic modeling, coadministration of trofinetide with orally administered midazolam, a sensitive CYP3A4 substrate, was predicted to increase the AUC of midazolam by approximately 1.33-fold [1].
References
1 ) Product Information: DAYBUE(TM) oral solution, trofinetide oral solution. Acadia Pharmaceuticals Inc (per FDA), San Diego, CA, 2023.
Avapritinib Overview
-
Avapritinib is used to treat a certain type of gastrointestinal stromal tumor (GIST; a type of tumor that grows in the wall of the stomach, intestine [bowel], or esophagus [tube that connects the throat with the stomach]) in adults that has spread to other parts of the body or that cannot be removed by surgery. It is also used to treat certain types of mastocytosis (a blood disorder in which there are too many mast cells [a certain kind of white blood cell]). Avapritinib 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.
Trofinetide Overview
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Trofinetide is used to treat Rett syndrome (an inherited condition that causes severe developmental and nervous system problems) in adult and children 2 years of age or older. Trofinetide is an analog of glycine-proline-glutamate (GPE), a protein that occurs naturally in the brain. It is not known exactly how trofinetide works, but it may improve nerve function and structure.
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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.