Drug Interaction Report

Leflunomide and Repaglinide: Interaction Details

A pharmacist-reviewed analysis of the Leflunomide and Repaglinide 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

Repaglinide

Prandin®
+

Leflunomide

Arava Arava®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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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 58 documented Leflunomide interactions, 52 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
probable
Severity
Major

What happens

Increased repaglinide exposure

Interaction Deep Dive

Coadministration of repaglinide (CYP2C8, OATP1B1 substrate) and leflunomide or its active metabolite, teriflunomide (CYP2C8, OATP1B1 inhibitor), may result in increased exposure to repaglinide. When repaglinide was administered following repeated doses of teriflunomide, the mean Cmax and AUC of repaglinide were increased by 1.7- and 2.4-fold, respectively. Monitor patients taking repaglinide and leflunomide or teriflunomide concomitantly21 and adjust the repaglinide dose, if necessary 23.

Why it happens (mechanism)

Inhibition of CYP2C8-mediated repaglinide metabolism by teriflunomide (the active metabolite of leflunomide); inhibition of OAT transport of repaglinide by teriflunomide

Literature reports

1 report — tap to read

a) Mean Cmax and AUC of repaglinide were increased by 1.7- and 2.4-fold, respectively, when repaglinide 0.25 mg was administered following repeated doses of teriflunomide 2, the active metabolite of leflunomide 1.

Common questions

Can I take Leflunomide and Repaglinide together?

Increased repaglinide exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Leflunomide and Repaglinide 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 Leflunomide or Repaglinide 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 (3)

  1. Product Information: ARAVA(R) oral tablets, leflunomide oral tablets. Sanofi-Aventis U.S. LLC (per FDA), Bridgewater, NJ, 2016. DailyMed
  2. Product Information: AUBAGIO(R) oral tablets, teriflunomide oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2014. DailyMed
  3. Product Information: PRANDIN(R) oral tablets, repaglinide oral tablets. Novo Nordisk Inc. (per FDA), Princeton, NJ, 2012. DailyMed
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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:

Repaglinide + Activated Charcoal Siberian Cocklebur Acai African Wild Potato Agaricus Mushroom Agmatine Agrimony Alfalfa + 248 more
Leflunomide + Activated Charcoal Beer Siberian Cocklebur Wine Ashwagandha Black Cohosh Boldo Buchu + 51 more

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

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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.