Drug & supplement interaction

Limonene + Efavirenz

Efavirenz brand name: Sustiva.

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

Efavirenz 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 Efavirenz

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. Efavirenz 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) INHIBITORS

1 of 2

Why this applies to Efavirenz

Efavirenz 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 know: in this interaction, it's the limonene that gets affected, not your efavirenz. Efavirenz can block the liver enzyme CYP2C19, and early lab work hints that limonene may be broken down by that same enzyme. So if you slow that enzyme down with efavirenz, limonene could build up a bit more than usual.

The honest part: this is based only on test-tube and animal data, and it has never actually been reported in people. Food amounts of citrus are not a concern. Efavirenz itself isn't a prodrug, so its HIV-fighting power and its usual side effects (like dizziness, vivid dreams, or trouble sleeping) shouldn't change here. Still, before starting a concentrated limonene supplement, run it by your pharmacist or HIV provider.

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 2

Efavirenz 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 thing to keep in mind: in this case it's the limonene that gets cleared by the CYP2C9 enzyme, not your efavirenz. Efavirenz can mildly block (inhibit) CYP2C9, so in theory it could slow down how fast your body breaks limonene down, letting a bit more of it linger. That might mean slightly stronger limonene effects, like mild stomach upset, but this is not expected to change how well your efavirenz controls your HIV.

The reassuring part: this idea comes only from lab and test-tube work, not from real people, so it's very theoretical. Food amounts of citrus are not a worry. If you're thinking about concentrated limonene capsules, just run it by your pharmacist or doctor first so they can check your full HIV regimen.

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 Efavirenz 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. Efavirenz)
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 Efavirenz

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Efavirenz page lists 159 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 117 moderate · 39 minor.

From our pharmacist’s overview on the Efavirenz page

“Efavirenz (Sustiva) is an HIV medicine, so an interaction that weakens it can cost more than a bad day; it can invite viral resistance. That makes this a list to treat with genuine care.”

Reviewed by 2 · Jul 18, 2026

Open the Efavirenz 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 Efavirenz 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 Efavirenz 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

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

29 days ago today
Medication Efavirenz
Steady interest

#1,643 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 Efavirenz

What Is Efavirenz Used For?

Brand name: Sustiva

Efavirenz is used to treat HIV-1 (human immunodeficiency virus type 1) infection. It is always used together with other antiretroviral medicines — never on its own.

It is approved for adults and for children who are at least 3 months old and weigh at least 3.5 kg (about 7.7 lbs). Both the capsule and tablet forms are approved for this use.

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

Can you take Limonene with Efavirenz?
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 Efavirenz?
Efavirenz 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 Efavirenz 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 Efavirenz 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.