Drug & supplement interaction

Limonene + Phenobarbital, Phenytoin

Phenobarbital, Phenytoin brand name: Dilantin with PB.

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

Phenobarbital, Phenytoin 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 2C9 (CYP2C9), as well causing its induction.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Phenobarbital, Phenytoin

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. Phenobarbital, Phenytoin 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 2C9 (CYP2C9) SUBSTRATES

1 of 3

Why this applies to Phenobarbital, Phenytoin

Phenobarbital, Phenytoin falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Limonene interacts with.

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. Phenytoin is one of those medicines where your blood level has to stay in a fairly narrow window to work well and stay safe. The concern with limonene is that, in lab and animal studies, it appears to speed up an enzyme called CYP2C9, which is one of the main pathways your body uses to clear phenytoin. If that enzyme runs faster, phenytoin could clear out a bit quicker and your level could drift down, which in theory could mean less seizure protection.

The honest part is that this has only been seen in test-tube and animal work, never confirmed in people, so it's a theoretical worry, not a proven one. A splash of citrus or orange peel in food won't matter. Concentrated limonene capsules are the real question. Because phenytoin is so dose-sensitive, please check with your pharmacist or doctor before adding a supplement.

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
Moderate

CYTOCHROME P450 2C19 (CYP2C19) INDUCERS

2 of 3

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2C19 (CYP2C19) INDUCERS.

There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C19 (CYP2C19). CYP2C19 inducers might decrease the effects of limonene. So far, this interaction has not been reported in humans. Inducers of CYP2C19 include carbamazepine (Tegretol), prednisone (Deltasone), and rifampin (Rifadin, Rimactane).
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: this interaction runs the opposite way from what people usually worry about. It's your seizure medicines (phenobarbital and phenytoin) that may affect the limonene, not the other way around. Both of these drugs are known to rev up liver enzymes, including CYP2C19, which is one pathway that breaks limonene down. So in theory, taking them together could clear the limonene faster and make it less effective. There's no good reason to expect your phenytoin or phenobarbital levels, or your seizure control, to change because of limonene.

Honestly, this is based only on lab and animal work, and it has never been seen in real people. Citrus you eat is no concern. If you're using concentrated limonene capsules, just mention it to your pharmacist or doctor.

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
Moderate

CYTOCHROME P450 2C9 (CYP2C9) INDUCERS

3 of 3

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2C9 (CYP2C9) INDUCERS.

There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9). Inducers of CYP2C9 might decrease limonene levels. Inducers of CYP2C9 include rifampin (Rifadin, Rimactane) and secobarbital (Seconal).
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 pairing, it's the limonene that may be affected, not your phenobarbital or phenytoin. Both of these seizure medicines speed up a liver enzyme called CYP2C9, which appears to help break limonene down. So if you take them together, your body may clear the limonene faster, meaning you'd likely get less of whatever benefit you were hoping for from the supplement.

The good news is your medication levels and seizure control should not be pushed around by the limonene here. And honestly, this is based only on early lab and animal work, not on people, so it's a fairly soft signal. Food amounts of citrus are nothing to worry about. Before adding a concentrated limonene supplement, just run it by your pharmacist or doctor first.

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

Moderate 228 No known interaction 2,602 (incl. Phenobarbital, Phenytoin)
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 Phenobarbital, Phenytoin

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital, Phenytoin page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 9 major · 192 moderate · 28 minor.

From our pharmacist’s overview on the Phenobarbital, Phenytoin page

“If your seizure medicine is the phenobarbital and phenytoin combination (Dilantin with PB), read this list carefully before you add any supplement. Nine of the 229 entries rate major, and most of the risk runs through two channels.”

Reviewed by 2 · Jul 18, 2026

Open the Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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

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

29 days ago today
Medication Phenobarbital, Phenytoin
Steady interest

#2,192 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
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
228 Moderate 2,601 No 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

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 2,601 medications checked with no known interaction — see the full Limonene list.

See the full Limonene interactions page
See every supplement checked against Phenobarbital, Phenytoin, 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 Phenobarbital, Phenytoin supplement interactions › Every supplement checked against Phenobarbital, Phenytoin, ranked by severity 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 Phenobarbital, Phenytoin Together: Common Questions

Can you take Limonene with Phenobarbital, Phenytoin?
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 Phenobarbital, Phenytoin?
Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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.