Drug & supplement interaction

Limonene + Phenobarbital, Sodium Nitrate

Phenobarbital, Sodium Nitrate brand name: Soniphen.

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

Phenobarbital, Sodium Nitrate 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 Phenobarbital, Sodium Nitrate

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. Phenobarbital, Sodium Nitrate 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) INDUCERS

1 of 2

Why this applies to Phenobarbital, Sodium Nitrate

Phenobarbital, Sodium Nitrate falls under CYTOCHROME P450 2C19 (CYP2C19) INDUCERS — the group Limonene interacts with.

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 understand: in this pairing, it's the limonene that may get affected, not your phenobarbital. Phenobarbital is a barbiturate that revs up certain liver enzymes, including CYP2C19. Since limonene appears to be broken down by that same enzyme, speeding it up could clear the limonene faster and weaken whatever benefit you were hoping to get from the supplement.

The good news is this is very gentle evidence, only seen in lab and animal studies, never reported in real people. Food amounts of citrus are not a concern. Your phenobarbital dose and its effects (drowsiness, calming, seizure control) shouldn't change because of limonene. Still, if you're taking concentrated limonene supplements, mention it to your pharmacist or doctor so they can keep an eye on things.

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

2 of 2

Phenobarbital, Sodium Nitrate 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 about this pairing: the interaction runs in the direction of the supplement, not your medicine. Phenobarbital is a known liver enzyme booster, and it can rev up the same pathway (CYP2C9) that helps break down limonene. So if anything, your phenobarbital may lower limonene levels, meaning the supplement might do less for you. It does not work the other way around, so this shouldn't make your phenobarbital stronger or weaker.

I want to be honest that this is built on early lab and animal data only, so it's more of a theoretical note than a proven problem. Everyday citrus in food is no concern. Before adding concentrated limonene capsules, just check with your pharmacist or doctor, since phenobarbital is a medication we like to keep steady.

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, Sodium Nitrate 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, Sodium Nitrate)
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, Sodium Nitrate

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital, Sodium Nitrate page lists 141 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: 8 major · 115 moderate · 18 minor.

From our pharmacist’s overview on the Phenobarbital, Sodium Nitrate page

“Phenobarbital with sodium nitrate (Soniphen) is a barbiturate, a heavy sedative used mainly for seizures, and its supplement list calls for real care before you add anything to it. Of the 141 ingredients on file, 78 pile extra sedation onto a drug that already slows breathing and reflexes, and six of the eight major-rated entries sit i…”

Reviewed by 2 · Jul 18, 2026

Open the Phenobarbital, Sodium Nitrate 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, Sodium Nitrate 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, Sodium Nitrate 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

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

29 days ago today
Medication Phenobarbital, Sodium Nitrate
Steady interest

#1,581 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, Sodium Nitrate, 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, Sodium Nitrate supplement interactions › Every supplement checked against Phenobarbital, Sodium Nitrate, 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, Sodium Nitrate Together: Common Questions

Can you take Limonene with Phenobarbital, Sodium Nitrate?
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 Phenobarbital, Sodium Nitrate?
Phenobarbital, Sodium Nitrate 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, Sodium Nitrate 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, Sodium Nitrate 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.