Selpercatinib and Everolimus: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Everolimus
Selpercatinib
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 CYP3A and P-gp substrate with NTI exposure and an increased risk of CYP3A and P-gp with NTI-related adverse events
Interaction Deep Dive
Avoid coadministration of selpercatinib (CYP3A and P-gp inhibitor) with a CYP3A4 and P-gp substrate with NTI as it may increase substrate with NTI exposure and may increase risk of these substrates-related adverse reaction. In a pharmacokinetic study, coadministration of selpercatinib with midazolam (a sensitive CYP3A substrate) increased midazolam AUC(0 to inf) by 54% and Cmax by 39%. And, coadministration of selpercatinib with dabigatran (a P-gp substrate) increased the dabigatran AUC(0 to inf) by 38% and Cmax by 43%. If concomitant use is necessary, follow recommendations for the P-gp substrate, as appropriate1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport by selpercatinib; inhibition of CYP3A-mediated metabolism by selpercatinib
Literature reports
2 reports — tap to read
a) Coadministration of selpercatinib with dabigatran (a P-gp substrate) increased the dabigatran AUC(0 to inf) by 38% and Cmax by 43% 1.
b) In a pharmacokinetic study, coadministration of selpercatinib with midazolam (a sensitive CYP3A substrate) increased midazolam AUC(0 to inf) by 54% and Cmax by 39% 1
Common questions
Can I take Selpercatinib and Everolimus together?
Increased CYP3A and P-gp substrate with NTI exposure and an increased risk of CYP3A and P-gp with NTI-related adverse events Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selpercatinib and Everolimus 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Selpercatinib or Everolimus 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: RETEVMO(R) oral capsules, tablets, selpercatinib oral capsules, tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2024. DailyMed
Keep reading about Everolimus
Keep reading about Selpercatinib
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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