Drug & supplement interaction

Limonene + Sacubitril, Valsartan

Sacubitril, Valsartan brand name: Entresto.

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

Limonene has a moderate interaction with Sacubitril, Valsartan. 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
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Sacubitril, Valsartan

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Why this applies to Sacubitril, Valsartan

Sacubitril, Valsartan 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 gist for Entresto (sacubitril/valsartan): the valsartan part is partly handled by a liver enzyme called CYP2C9. Lab and animal research hints that concentrated limonene supplements might speed that enzyme up. If that happened in people, your body could clear valsartan a little faster, which could make Entresto work slightly less well at managing your heart failure and blood pressure.

I want to be honest about how soft this is. This has never actually been reported in humans, and it comes only from test-tube and animal data. The orange or lemon you eat won't matter at all. If you're considering a concentrated limonene supplement, just run it by your pharmacist or doctor first so they can keep an eye on your blood pressure and symptoms.

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 Sacubitril, Valsartan one above is one of them. If you take anything else, check it against the full list below.

Moderate 228 No known interaction 2,602 (incl. Sacubitril, Valsartan)
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 Sacubitril, Valsartan

This page covers Limonene only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sacubitril, Valsartan page lists 249 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Lithium (major) and Oleander (major).

By severity: 7 major · 206 moderate · 36 minor.

From our pharmacist’s overview on the Sacubitril, Valsartan page

“Entresto (sacubitril and valsartan) is a heart failure medicine, and heart failure patients tend to be heavy supplement users, reaching for fish oil, potassium, and herbal blood-pressure remedies. That instinct carries real risk here.”

Reviewed by 2 · Jul 18, 2026

Open the Sacubitril, Valsartan 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 Sacubitril, Valsartan 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 Sacubitril, Valsartan 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

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

29 days ago today
Medication Sacubitril, Valsartan
Top 25%

#326 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 Valsartan and Sacubitril

What Is Valsartan and Sacubitril Used For?

Brand name: Entresto

Sacubitril and valsartan is used to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. The benefit is most clearly seen in patients whose heart pumps with a lower-than-normal ejection fraction (the percentage of blood the heart pushes out with each beat).

It is also approved to treat symptomatic heart failure with reduced left ventricular function in children aged 1 year and older. In pediatric patients, it lowers a blood marker of heart stress (NT-proBNP) and is expected to improve heart outcomes.

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

Can you take Limonene with Sacubitril, Valsartan?
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.
How serious is the Limonene and Sacubitril, Valsartan 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 Sacubitril, Valsartan 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.