Drug & supplement interaction

Limonene + Leflunomide

Leflunomide brand name: Arava.

Moderate Interaction
Medically reviewed by · Updated October 2026
The bottom line Moderate

Limonene has a moderate interaction with Leflunomide. There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9).

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Leflunomide

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS

Why this applies to Leflunomide

Leflunomide falls under CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS — the group Limonene interacts with.

There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9). So far, this interaction has not been reported in humans. However, watch for side effects in patients taking limonene and CYP2C9 inhibitors. Some CYP2C9 inhibitors include amiodarone (Cordarone), fluconazole (Diflucan), lovastatin (Mevacor), paroxetine (Paxil), zafirlukast (Accolate), and many others.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for leflunomide (Arava). Once you take it, your body turns it into its active form called teriflunomide, and that active piece is partly handled by a liver enzyme known as CYP2C9. Leflunomide's active metabolite can actually slow down (inhibit) that same enzyme. The concern on file is that limonene appears to lean on CYP2C9 too, based only on lab and animal work, not real human cases.

In plain terms, if leflunomide is busy occupying CYP2C9, limonene might clear more slowly and build up a bit. This is theoretical, and ordinary citrus-flavored foods are very unlikely to matter. If you're using a concentrated limonene supplement, just run it by your pharmacist or doctor first and watch for things like upset stomach or diarrhea.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129:775S-778S. PubMed
  2. Miyazawa M, Shindo M, Shimada T. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos 2002;30:602-7. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Limonene Also Interacts With Other Medications

Limonene has 229 moderate known drug interactions in our database — the Leflunomide one above is one of them. If you take anything else, check it against the full list below.

Moderate 229 No known interaction 2,601 (incl. Leflunomide)
Taking anything else?

Check Another of Your Medications Against Limonene

Covers the 2,830 medications we’ve checked against Limonene. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Leflunomide

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Leflunomide page lists 59 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Siberian Cocklebur (major), Wine (major) and Ashwagandha (moderate).

By severity: 4 major · 46 moderate · 9 minor.

From our pharmacist’s overview on the Leflunomide page

“Leflunomide (Arava) quiets rheumatoid arthritis by damping down the immune system, and its best-known danger is liver injury, so the 59 supplements and herbs on this page are worth slowing down for. Thirty-eight of them carry liver risks of their own, and of the four rated major, two are simply alcoholic drinks, while a third, Siberian…”

Reviewed by 2 · Jul 18, 2026

Open the Leflunomide interaction page

One more smart check

Taking Limonene as Part of a Dietary Supplement Product? Check It for Interactions

We hold 89 real supplement products containing Limonene, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Limonene. Your product may carry other ingredients that interact with Leflunomide too, on top of Limonene — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Limonene and Leflunomide Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Limonene
Top half

#678 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Leflunomide
Top 25%

#700 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Limonene

What is Limonene?

  • Heartburn and acid reflux
  • Digestive upset
  • Stress and mood support
  • Antioxidant support
  • General wellness

Limonene is a natural compound found in the peel of citrus fruits like oranges and lemons, and it is used as a flavoring agent and dietary supplement. People take it for heartburn, digestion, and general wellness, but solid human evidence is limited. It is generally well tolerated in food amounts, but talk with your pharmacist or doctor before using concentrated supplements.

Read the full Limonene monograph & all interactions
Medication

About Leflunomide

What Is Leflunomide Used For?

Brand name: Arava

Leflunomide is used to treat active rheumatoid arthritis (RA) in adults. RA is a long-term condition in which the immune system attacks the joints.

This use applies to Arava and to leflunomide tablets (including film-coated tablets) from other makers.

See full Leflunomide drug information
Keep checking

Other Drugs & Limonene

Browse every other medication we’ve checked against Limonene — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
229Moderate
0Minor
2,600No known interaction
229 Moderate 2,600 No interaction
Moderate

229 interactions

Showing 60 of 229 moderate interactions — see all 229 on the Limonene page.

No interaction 2,600 drugs checked — show the list

We also checked Limonene against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,600 medications checked with no known interaction — see the full Limonene list.

See the full Limonene interactions page
See every supplement checked against Leflunomide, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Limonene monograph › Uses, safety, and every drug interaction in one place Leflunomide supplement interactions › Every supplement checked against Leflunomide, ranked by severity Leflunomide drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Limonene and Leflunomide Together: Common Questions

Can you take Limonene with Leflunomide?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Limonene and Leflunomide interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Leflunomide and Limonene?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.