Drug & supplement interaction

Limonene + Enzalutamide

Enzalutamide brand name: Xtandi.

Moderate Interaction
The bottom line Moderate

Enzalutamide 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 Enzalutamide

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. Enzalutamide 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 Enzalutamide

Enzalutamide 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 about this pairing: the concern runs in one direction, and it's the limonene that may take the hit, not your Xtandi. Enzalutamide is a strong inducer of the CYP2C19 enzyme, meaning it speeds that pathway up. Since limonene appears to be broken down by CYP2C19, taking it alongside enzalutamide could clear the limonene out faster, leaving you with less of whatever benefit you were hoping to get from it.

The good news is your prostate cancer treatment shouldn't be weakened by limonene here, so this isn't a reason to worry about your therapy failing. This is also only lab-based evidence and has never been reported in real people. Casual citrus in food is a non-issue. Before adding a concentrated limonene supplement, just run it by your oncology pharmacist.

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

Enzalutamide 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 cancer medicine. Enzalutamide (Xtandi) actually speeds up a liver enzyme called CYP2C9, and early lab work suggests limonene may be broken down by that same enzyme. So in theory, taking enzalutamide could clear limonene out of your body faster, leaving less of the supplement around to do whatever you're hoping it does.

Importantly, this does not appear to make your enzalutamide stronger or weaker, and it shouldn't change how well it fights your prostate cancer. The evidence here is only from test-tube and animal studies, so it's pretty preliminary. Food amounts of citrus are unlikely to matter. Still, before starting a concentrated limonene supplement during cancer treatment, please run it by your oncology team or pharmacist first.

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 Enzalutamide one above is among them. If you take anything else, check it against the full list below.

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 Enzalutamide

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Enzalutamide page lists 49 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Alkanna (moderate), Alpine Ragwort (moderate), Black Tea (moderate) and Boneset (moderate).

By severity: 1 major · 36 moderate · 12 minor.

Open the Enzalutamide 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 Enzalutamide 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 Enzalutamide 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 Enzalutamide
Top 10%

#182 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 Enzalutamide

What Is Enzalutamide Used For?

Brand name: Xtandi

Xtandi (enzalutamide) is used to treat prostate cancer in three specific situations: castration-resistant prostate cancer (CRPC), metastatic castration-sensitive prostate cancer (mCSPC), and non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis (high-risk BCR).

Castration-resistant means the cancer has continued to grow despite low testosterone levels. Castration-sensitive means the cancer still responds to testosterone-lowering therapy. In most of these cases, Xtandi is used alongside a GnRH analog (a hormone-lowering injection) or after surgical removal of the testicles — except in the high-risk BCR setting, where it may be used with or without a GnRH analog.

See full Enzalutamide 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
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
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

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Pharmacist Counseling Corner

Taking Limonene and Enzalutamide Together: Common Questions

Can you take Limonene with Enzalutamide?
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 Enzalutamide?
Enzalutamide 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 Enzalutamide 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

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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.