Drug & supplement interaction

Limonene + Isoniazid, Rifampin

Isoniazid, Rifampin brand name: Rifamate.

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

Isoniazid, Rifampin falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Isoniazid, Rifampin

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Limonene interacts with whole categories of medication. Isoniazid, Rifampin falls into 4 of those categories, so it can interact with Limonene in 4 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 4

Why this applies to Isoniazid, Rifampin

Isoniazid, Rifampin 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 thing to keep in mind with this pairing. Isoniazid is known to slow down the CYP2C19 enzyme, and early lab work hints that limonene may be processed by that same enzyme. So in theory, taking concentrated limonene alongside isoniazid could let limonene build up a bit higher in your system. Notice the direction here: it's the supplement that may rise, not your TB medicine. Your isoniazid and rifampin should keep working as expected.

Honestly, this is only seen in test tube and animal studies, and it has never been reported in real people, so I wouldn't lose sleep over it. The small amount of limonene in citrus or food flavoring is very unlikely to matter. Before starting a strong limonene supplement, just run it past 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) INHIBITORS

2 of 4

Isoniazid, Rifampin 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 understand: in this interaction, limonene is the one being affected, not your medicine. Limonene appears to be broken down by an enzyme called CYP2C9, and isoniazid (one of the drugs in Rifamate) can slow that enzyme down. If limonene is cleared more slowly, more of it can build up in your body. That mostly means a higher chance of limonene-related effects, not changes to how well your TB medication works.

The honest bottom line: this is only based on lab data and has never actually been seen in people, so I wouldn't lose sleep over it. Food amounts of citrus are not a concern. Still, before adding a concentrated limonene supplement to a regimen like Rifamate, 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
Moderate

CYTOCHROME P450 2C19 (CYP2C19) INDUCERS

3 of 4

Isoniazid, Rifampin 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 the direction is actually the reverse of what people usually worry about. The combination pill Rifamate (isoniazid plus rifampin) isn't the drug being affected here. Instead, rifampin is a strong enzyme booster that revs up CYP2C19, one of the liver pathways that breaks down limonene. So if you take a limonene supplement alongside Rifamate, your body may clear the limonene faster, leaving less of it around to do whatever you were hoping it would do.

This is very early lab and animal data, not something seen in real patients, so I wouldn't lose sleep over it. The bigger point: your isoniazid and rifampin keep working as usual, but the limonene may simply be weaker. Run any new supplement past your pharmacist while you're on this medication.

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

4 of 4

Isoniazid, Rifampin 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 to keep in mind: this interaction runs in one direction, and it's the limonene that gets affected, not your medication. Rifampin (part of Rifamate, along with isoniazid) is a strong booster of a liver enzyme called CYP2C9. Since limonene appears to be broken down by that same enzyme, taking rifampin may speed up how fast your body clears the limonene, leaving less of it around. In short, your supplement may simply not do much for you.

The good news is your tuberculosis treatment shouldn't be weakened by limonene, and there's no expected boost in side effects like nausea or liver irritation from this combo. This is based only on lab data, so it's far from certain. Still, mention any supplements to your pharmacist or doctor, since TB therapy is important to get right.

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 Isoniazid, Rifampin 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. Isoniazid, Rifampin)
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 Isoniazid, Rifampin

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Isoniazid, Rifampin page lists 145 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Asarabacca (major), Beer (major) and Grapefruit (major).

By severity: 8 major · 117 moderate · 20 minor.

From our pharmacist’s overview on the Isoniazid, Rifampin page

“Rifamate combines isoniazid and rifampin, the backbone of tuberculosis treatment, and both drugs are hard on the liver, which is why this list of 145 supplement and herbal interactions deserves genuine respect. Eight entries rate major, and the largest cluster, 38 ingredients, adds to that same liver strain, with alcohol in beer or win…”

Reviewed by 2 · Jul 18, 2026

Open the Isoniazid, Rifampin 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 Isoniazid, Rifampin 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 Isoniazid, Rifampin 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

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

29 days ago today
Medication Isoniazid, Rifampin
Top 25%

#665 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 Isoniazid, Rifampin, 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 Isoniazid, Rifampin supplement interactions › Every supplement checked against Isoniazid, Rifampin, 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 Isoniazid, Rifampin Together: Common Questions

Can you take Limonene with Isoniazid, Rifampin?
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 4 interactions listed for Limonene and Isoniazid, Rifampin?
Isoniazid, Rifampin 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 Isoniazid, Rifampin 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 Isoniazid, Rifampin 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.