Nateglinide and Simeprevir: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Simeprevir
Nateglinide
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 exposure of nateglinide
Interaction Deep Dive
Coadministering simeprevir (an OATP1B1 inhibitor and a mild intestinal CYP3A4 inhibitor) with nateglinide (an OATP1B1 substrate and a CYP3A4 substrate) is not recommended as it may cause increased exposure of nateglinide1.
Why it happens (mechanism)
Inhibition of OATP1B1-mediated nateglinide efflux transport; inhibition of CYP3A4-mediated nateglinide metabolism
Common questions
Can I take Nateglinide and Simeprevir together?
Increased exposure of nateglinide Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nateglinide and Simeprevir 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 Nateglinide or Simeprevir 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: OLYSIO(R) oral capsules, simeprevir oral capsules. Janssen Therapeutics (per manufacturer), Titusville, NJ, 2014.
Keep reading about Simeprevir
Keep reading about Nateglinide
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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