Drug & supplement interaction

Limonene + Fosphenytoin

Fosphenytoin brand name: Cerebyx.

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

Fosphenytoin 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 Fosphenytoin

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. Fosphenytoin 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 Fosphenytoin

Fosphenytoin 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 situation with Cerebyx (fosphenytoin). Once it's in your body, fosphenytoin gets converted into phenytoin, the active seizure-fighting drug, and phenytoin is cleared in part by a liver enzyme called CYP2C9. There's early lab and animal evidence that limonene may speed that enzyme up (induce it). If that happened in people, your body could clear phenytoin a little faster, which might lower its blood level and, in theory, make it less effective at keeping seizures controlled.

I want to be honest though: this has not been reported in actual patients, and it comes from test-tube and animal studies. Casual citrus in your diet almost certainly won't matter. The concern is more about concentrated limonene supplements. Because phenytoin is a finicky drug where small changes count, please check with your doctor or pharmacist before adding one.

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

Fosphenytoin 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 about this pairing: the interaction runs in one direction, and it's the medication affecting the supplement, not the other way around. Fosphenytoin (which your body converts to phenytoin) tends to rev up a liver enzyme called CYP2C19. Since limonene appears to be broken down by that same enzyme, taking it alongside fosphenytoin could speed up how fast limonene clears out, which may simply make the supplement less effective for you.

The good news is that this is based only on lab and animal work, not real human reports, so it's pretty theoretical. There's no solid sign that limonene changes your fosphenytoin or seizure control. Still, fosphenytoin is a careful-dosing medication, so I'd run any supplement past 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
Moderate

CYTOCHROME P450 2C9 (CYP2C9) INDUCERS

3 of 3

Fosphenytoin 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 thing worth understanding: this interaction runs the opposite way from what most people expect. Fosphenytoin (which your body converts to phenytoin) is a strong inducer of the liver enzyme CYP2C9. The concern on file isn't that limonene changes your fosphenytoin levels. It's that fosphenytoin may speed up how fast your body clears limonene, which could leave less of the supplement around to do whatever you're taking it for.

The good news is this is based only on lab and animal data, so it's a fairly soft, theoretical signal. Food amounts of citrus oils almost certainly don't matter. Since fosphenytoin is a seizure medicine with a narrow safe range, I wouldn't expect a concentrated limonene supplement to throw off your seizure control, but please run it by your pharmacist or neurologist before adding it.

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 Fosphenytoin 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. Fosphenytoin)
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 Fosphenytoin

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosphenytoin page lists 205 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 14 major · 172 moderate · 19 minor.

From our pharmacist’s overview on the Fosphenytoin page

“St. John's wort is the entry I would flag first with fosphenytoin (Cerebyx).”

Reviewed by 2 · Jul 18, 2026

Open the Fosphenytoin 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 Fosphenytoin 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 Fosphenytoin 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

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

29 days ago today
Medication Fosphenytoin
Steady interest

#2,051 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 Fosphenytoin Injection

What Is Fosphenytoin Injection Used For?

Brand name: Cerebyx

Fosphenytoin injection is used to treat generalized tonic-clonic status epilepticus (a prolonged, life-threatening seizure emergency) and to prevent or treat seizures that occur during or after brain surgery. It is given by intravenous (IV) or intramuscular (IM) injection in a hospital or clinical setting.

It can also be used short-term as a substitute for oral phenytoin when a patient cannot take medicine by mouth. This use is temporary — as soon as oral phenytoin is possible again, it should replace the injection.

See full Fosphenytoin Injection 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
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 Fosphenytoin, 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 Fosphenytoin supplement interactions › Every supplement checked against Fosphenytoin, ranked by severity Fosphenytoin Injection 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 Fosphenytoin Together: Common Questions

Can you take Limonene with Fosphenytoin?
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 Fosphenytoin?
Fosphenytoin 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 Fosphenytoin 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 Fosphenytoin 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.