Drug & supplement interaction

Limonene + Ketoconazole

Ketoconazole brand name: Nizoral.

Moderate Interaction
The bottom line Moderate

Ketoconazole falls into 2 drug categories that Limonene can interact with; the most serious is rated moderate. There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C19 (CYP2C19).

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Ketoconazole

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Limonene interacts with whole categories of medication. Ketoconazole falls into 2 of those categories, so it can interact with Limonene in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C19 (CYP2C19) INHIBITORS

1 of 2

Why this applies to Ketoconazole

Ketoconazole falls under CYTOCHROME P450 2C19 (CYP2C19) INHIBITORS — the group Limonene interacts with.

There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C19 (CYP2C19). So far, this interaction has not been reported in humans. However, watch for an increase in the limonene levels when it is taken with drugs that inhibit CYP2C19. Some drugs that inhibit CYP2C19 include cimetidine (Tagamet), fluvoxamine (Luvox), omeprazole (Prilosec); ticlopidine (Ticlid), topiramate (Topamax), and 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 key thing to understand: in this interaction, it's the limonene that's affected, not your ketoconazole. Ketoconazole is a strong blocker of several liver enzymes, including CYP2C19. Early lab work suggests limonene may be broken down by that same enzyme. So when you pair them, ketoconazole could slow limonene's breakdown and let it build up a bit in your body.

The good news is this is very theoretical. It comes only from test tube and animal data, has never been reported in real people, and limonene in everyday food amounts (like the oils in citrus peel) is unlikely to matter. With concentrated limonene supplements, it's worth a quick chat with your pharmacist or doctor first, just to be safe.

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
Moderate

CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS

2 of 2

Ketoconazole also falls under CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS.

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 thing to keep in mind: this interaction is really about the limonene, not your ketoconazole. Ketoconazole is a strong blocker of several liver enzymes, including CYP2C9. Lab research hints that limonene may be broken down by that same enzyme. So if ketoconazole slows that pathway down, the limonene could hang around longer in your body than usual.

Honestly, though, this is theoretical. It comes from test tube and animal work, and it has not been reported in real people. Your ketoconazole itself should work the same. Since limonene supplements are concentrated (regular citrus in food is not a worry), just check with your pharmacist before adding one, and watch for any unusual stomach upset or feeling off.

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 228 moderate known drug interactions in our database — the Ketoconazole one above is among them. If you take anything else, check it against the full list below.

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.

From our Q&A

Questions About Limonene or Ketoconazole

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Limonene or Ketoconazole, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Ketoconazole

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ketoconazole page lists 182 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 135 moderate · 41 minor.

From our pharmacist’s overview on the Ketoconazole page

“Ketoconazole (Nizoral) is already hard on the liver, so treat its 182 interacting supplements with genuine care, starting with the six rated major. Most of the list runs through CYP3A4, the liver enzyme ketoconazole strongly blocks, so it can raise levels of over a hundred herbal ingredients, while grapefruit pushes ketoconazole itself…”

Reviewed by 2 · Jul 18, 2026

Open the Ketoconazole 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 Ketoconazole 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 Ketoconazole 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
Steady interest

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

29 days ago today
Medication Ketoconazole
Steady interest

#1,985 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 Ketoconazole

What Is Ketoconazole Used For?

Brand name: Nizoral

Ketoconazole 2% shampoo and foam are used to treat tinea versicolor (also called pityriasis versicolor) — a fungal infection caused by Pityrosporum orbiculare (also known as Malassezia furfur), a yeast that naturally lives on the skin.

This infection creates light or dark patches, most often on the trunk, neck, arms, and upper thighs. Even after the fungus is cleared, those skin patches may take months to return to their normal color — that's normal, and depends on your skin type and sun exposure. Tinea versicolor can also come back, since the fungus lives on healthy skin even when there's no active infection.

See full Ketoconazole 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
228Moderate
0Minor
2,601No known interaction
Moderate

228 interactions

Showing 60 of 228 moderate interactions — see all 228 on the Limonene page.

No interaction 2,601 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Limonene and Ketoconazole Together: Common Questions

Can you take Limonene with Ketoconazole?
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.
Why are there 2 interactions listed for Limonene and Ketoconazole?
Ketoconazole belongs to more than one drug category, and Limonene interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Limonene and Ketoconazole 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 Ketoconazole 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.