Everolimus and Trofinetide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Trofinetide
Everolimus
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased sensitive CYP3A/P-gp substrate with NTI exposure and an increased risk of sensitive CYP3A/P-gp substrate with NTI substrate-related toxicities
Interaction Deep Dive
Concomitant use of trofinetide (weak CYP3A inhibitor and P-gp inhibitor) with sensitive CYP3A substrates that also are P-gp substrates with NTI may increase these substrates exposure, which may increase the risk of these substrates-related adverse reactions. If coadministered, closely monitor as it may lead to serious adverse reactions. In a drug interaction study, coadministration of trofinetide 12,000 mg twice daily with 4 mg of loperamide (a moderately sensitive CYP3A substrate and a P-gp substrate) increased the AUC of loperamide by 1.73-fold and the Cmax by 1.95-fold. Administration of trofinetide 2 hours prior to loperamide increased the AUC of loperamide by 1.22-fold and the Cmax by 1.44-fold1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport by trofinetide; inhibition of CYP3A substrate metabolism by trofinetide
Literature reports
1 report — tap to read
a) In a drug interaction study, coadministration of trofinetide 12,000 mg twice daily with 4 mg of loperamide (a moderately sensitive CYP3A substrate and a P-gp substrate) increased the AUC of loperamide by 1.73-fold and the Cmax by 1.95-fold. Administration of trofinetide 2 hours prior to loperamide increased the AUC of loperamide by 1.22-fold and the Cmax by 1.44-fold 1.
Common questions
Can I take Everolimus and Trofinetide together?
Increased sensitive CYP3A/P-gp substrate with NTI exposure and an increased risk of sensitive CYP3A/P-gp substrate with NTI substrate-related toxicities Always confirm with your pharmacist or prescriber before making any change.
How serious is the Everolimus and Trofinetide interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Everolimus or Trofinetide need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: DAYBUE(R) oral solution, trofinetide oral solution. Acadia Pharmaceuticals Inc (per FDA), San Diego, CA, 2025. DailyMed
Keep reading about Trofinetide
Keep reading about Everolimus
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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