Drug Interaction Report

Selpercatinib and Cyclosporine Injection: Interaction Details

A pharmacist-reviewed analysis of the Selpercatinib and Cyclosporine Injection interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Selpercatinib

Retevmo Retevmo®
+

Cyclosporine Injection

Atopica Cequa Cyclavance Gengraf Modulis Neoral Optimmune Restasis
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
LinkedIn
Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 103 documented Selpercatinib interactions, 99 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased exposure of selpercatinib and cycloSPORINE and increased risk of adverse effects

Interaction Deep Dive

Concomitant use of selpercatinib (a CYP3A substrate, weak inhibitor of CYP3A, and P-gp inhibitor) with cycloSPORINE (a moderate CYP3A inhibitor, a CYPA substrate with a narrow therapeutic index (NTI), and a P-gp substrate with an NTI) should be avoided because significant increases in exposure of both drugs may increase the risk of adverse effects, including QTc interval prolongation. If coadministration is required, reduce selpercatinib dosage, increase the frequency of QT interval monitoring, and follow the recommendations for cycloSPORINE as appropriate. Reduce selpercatinib 160 mg twice daily to 120 mg twice daily and 120 mg twice daily to 80 mg twice daily. After cycloSPORINE has been discontinued for 3 to 5 half-lives, resume selpercatinib at the dose taken prior1.

Why it happens (mechanism)

Inhibition of CYP3A-mediated metabolism of one or both drugs; inhibition of P-gp-mediated efflux transport of cycloSPORINE; additive QT-interval prolongation

Literature reports

3 reports — tap to read

a) In a pharmacokinetic study, coadministration of selpercatinib with midazolam (a sensitive CYP3A substrate) increased midazolam AUC(0 to infinity) by 54% and Cmax by 39% 2.

b) Simulated coadministration of multiple doses of diltiazem, fluconazole, or verapamil (moderate CYP3A inhibitors) is predicted to increase selpercatinib AUC by 60% to 99% and Cmax by 46% to 76% 2.

c) Coadministration of selpercatinib with dabigatran (a P-gp substrate) increased the dabigatran AUC(0 to infinity) by 38% and Cmax by 43% 1.

Common questions

Can I take Selpercatinib and Cyclosporine Injection together?

Increased exposure of selpercatinib and cycloSPORINE and increased risk of adverse effects Always confirm with your pharmacist or prescriber before making any change.

How serious is the Selpercatinib and Cyclosporine Injection 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 Selpercatinib or Cyclosporine Injection 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 (2)

  1. Product Information: RETEVMO(TM) oral capsules, selpercatinib oral capsules. Lilly USA LLC (per FDA), Indianapolis, IN, 2022. DailyMed
  2. Product Information: RETEVMO(TM) oral capsules, selpercatinib oral capsules. Lilly USA LLC (per FDA), Indianapolis, IN, 2020. DailyMed
Was this write-up helpful?
Selpercatinib

Keep reading about Selpercatinib

All Selpercatinib interactions (103) Selpercatinib drug information
Also serious with: Ketoconazole Topical Oxaliplatin Injection Levofloxacin Injection Eribulin Injection
Cyclosporine Injection

Keep reading about Cyclosporine Injection

All Cyclosporine Injection interactions (545) Cyclosporine Injection drug information
Also serious with: Ezetimibe Grazoprevir Sitaxsentan Simvastatin
Beyond drug–drug

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:

Selpercatinib + Activated Charcoal American Hellebore Arsenic Beer Cesium Ephedra Grapefruit Siberian Cocklebur + 170 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist
This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.