Drug & supplement interaction

Limonene + Voriconazole

Voriconazole brand name: Vfend.

Moderate Interaction
The bottom line Moderate

Voriconazole falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Voriconazole

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Limonene interacts with whole categories of medication. Voriconazole falls into 3 of those categories, so it can interact with Limonene in 3 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 3

Why this applies to Voriconazole

Voriconazole 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 about this pairing: the interaction runs in the opposite direction from what most people assume. Voriconazole blocks an enzyme called CYP2C19, and limonene appears to be broken down by that same enzyme. So it's the limonene levels that could creep up, not the voriconazole. Voriconazole is the active drug working on its own (it's not a prodrug being switched on here), so its antifungal job shouldn't change.

The honest truth is that this is very early, lab-only evidence that hasn't been seen in real people, so I wouldn't lose sleep over it. The amount of limonene you'd get from an orange is a non-issue. If you're using concentrated limonene capsules alongside your Vfend, just give your pharmacist or doctor a heads-up first.

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 3

Voriconazole 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 key thing to know: in this interaction, limonene is the one being affected, not voriconazole. Limonene appears to be broken down partly by an enzyme called CYP2C9, and voriconazole happens to block that same enzyme. So if you take both, your body may clear limonene more slowly, which could let more of it build up and raise the odds of limonene-related effects.

The good news is this is very preliminary. It comes only from lab and animal data, and it has not actually been reported in people. Food amounts of citrus are not a concern. If you're using a concentrated limonene supplement alongside voriconazole, it's worth a quick chat with your pharmacist, but there's no need to panic.

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) SUBSTRATES

3 of 3

Voriconazole also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9), as well causing its induction. So far, this interaction has not been reported in humans. However, watch for a decrease in the levels of drugs metabolized by CYP2C9 in patients taking limonene. Some drugs metabolized by CYP2C9 include nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Cataflam, Voltaren), ibuprofen (Motrin), meloxicam (Mobic), and piroxicam (Feldene); celecoxib (Celebrex); amitriptyline (Elavil); warfarin (Coumadin); glipizide (Glucotrol); losartan (Cozaar); 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 gist for Vfend (voriconazole). Your body relies on a liver enzyme called CYP2C9 to help process this antifungal. Early lab research hints that limonene might speed that enzyme up (induce it). If that happened in people, your body could clear voriconazole a little faster, which might pull its blood levels down. That matters because voriconazole needs to stay in a fairly specific range to actually knock out a serious fungal infection.

The honest part: this is only test-tube and animal data, and it has not been seen in real patients. Everyday citrus in food is very unlikely to cause trouble. Concentrated limonene capsules are the bigger question mark. Since voriconazole is treating something serious, please run any supplement past your pharmacist or doctor first.

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 Voriconazole 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.

Everything else you take

See Every Supplement That Interacts With Voriconazole

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Voriconazole page lists 205 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 · 159 moderate · 40 minor.

From our pharmacist’s overview on the Voriconazole page

“Voriconazole (Vfend) is a heavy-hitter antifungal, usually prescribed for dangerous infections like invasive aspergillosis, and its list of 205 interacting supplements includes six rated major, enough that anyone on this drug should read those entries before touching a supplement bottle. Most interactions run through the liver enzymes…”

Reviewed by 2 · Jul 18, 2026

Open the Voriconazole 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 Voriconazole 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 Voriconazole 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

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

29 days ago today
Medication Voriconazole
Steady interest

#1,801 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 Voriconazole

What Is Voriconazole Used For?

Brand name: Vfend

Voriconazole treats several serious fungal infections. Across all available forms — tablets, oral suspension, and intravenous (IV) injection — it is used for invasive aspergillosis (a dangerous mold infection), candidemia (Candida fungus in the bloodstream) in patients who are not neutropenic (not severely low on white blood cells), other deep-tissue Candida infections, and serious infections caused by Scedosporium apiospermum or Fusarium species in patients who cannot tolerate or have not responded to other antifungal treatments.

Esophageal candidiasis (a Candida infection of the esophagus, the swallowing tube) is also an approved use for most formulations. Note on the oral tablet form (generic voriconazole tablets): that specific tablet formulation is approved for patients aged 12 to 14 years weighing at least 50 kg, and all patients 15 years and older — not for younger or smaller children. The oral suspension and the IV injection are approved for patients 2 years and older for most of these conditions.

See full Voriconazole 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 Voriconazole Together: Common Questions

Can you take Limonene with Voriconazole?
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 3 interactions listed for Limonene and Voriconazole?
Voriconazole 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 Voriconazole 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

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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.