Leflunomide and Acyclovir: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Leflunomide
Acyclovir
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 OAT3 substrate
Interaction Deep Dive
Teriflunomide, the active metabolite of leflunomide, inhibits the activity of Organic Anion Transporter 3 (OAT3). The mean Cmax and AUC of cefaclor were increased by 1.43- and 1.54-fold, respectively, when cefaclor was administered following repeated doses of teriflunomide. Exposure to other drugs that are substrates of OAT3 may be increased in patients taking leflunomide. Monitor these patients and adjust the dose of the concomitant drugs as required1.
Why it happens (mechanism)
Inhibition of OAT3 transport by leflunomide
Common questions
Can I take Leflunomide and Acyclovir together?
Increased exposure of OAT3 substrate Always confirm with your pharmacist or prescriber before making any change.
How serious is the Leflunomide and Acyclovir 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 Leflunomide or Acyclovir 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: ARAVA(R) oral tablets, leflunomide oral tablets. Sanofi-Aventis U.S. LLC (per FDA), Bridgewater, NJ, 2016. DailyMed
Keep reading about Leflunomide
Keep reading about Acyclovir
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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