Drug & supplement interaction

Grapefruit + Diclofenac

Diclofenac brand name: Zorvolex.

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

Grapefruit has a moderate interaction with Diclofenac. Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Diclofenac

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

Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Why this applies to Diclofenac

Diclofenac falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Grapefruit interacts with.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes. So far, this interaction has not been reported in humans.
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: your body clears diclofenac mainly through a liver enzyme called CYP2C9. Grapefruit may slow that enzyme down a little, and since diclofenac is active as-is (not a prodrug that needs switching on), slowing its breakdown could let a bit more of it linger in your system. In theory, that might nudge up the usual NSAID-type side effects, things like stomach upset, heartburn, fluid retention, or higher blood pressure.

The important part: this concern comes only from lab and test-tube studies, and it has never actually been reported in real patients. So I wouldn't lose sleep over an occasional grapefruit. Still, if you eat it regularly or use it as a supplement, 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. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 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

Grapefruit Also Interacts With Other Medications

Grapefruit has 776 major, 150 moderate, 63 minor known drug interactions in our database — the Diclofenac one above is one of them. If you take anything else, check it against the full list below.

Major 776 Moderate 150 Minor 63 No known interaction 1,841 (incl. Diclofenac)
Taking anything else?

Check Another of Your Medications Against Grapefruit

Covers the 2,830 medications we’ve checked against Grapefruit. Pick one to open its full report.

From our Q&A

Questions About Grapefruit or Diclofenac

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grapefruit or Diclofenac, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Diclofenac

This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diclofenac page lists 306 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 7 major · 265 moderate · 34 minor.

From our pharmacist’s overview on the Diclofenac page

“Diclofenac (Zorvolex) is an NSAID pain reliever that already stresses the stomach lining and kidneys on its own, so treat this list as a real safety issue, not fine print. Two thirds of the 306 supplements on file can thin the blood or slow clotting, and stacked on an NSAID that raises the odds of stomach bleeding.”

Reviewed by 2 · Jul 18, 2026

Open the Diclofenac interaction page

One more smart check

Taking Grapefruit as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Diclofenac too, on top of Grapefruit — 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 Grapefruit and Diclofenac 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 Grapefruit
Top 10%

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

29 days ago today
Medication Diclofenac
Top half

#850 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 Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Medication

About Diclofenac

What Is Diclofenac Used For?

Brand name: Zorvolex

Diclofenac sodium topical gel is used to treat actinic keratoses (AK) — rough, scaly skin patches that form after years of sun exposure. These patches are considered precancerous, meaning they can develop into skin cancer if left untreated.

This is a topical gel, meaning it is applied directly to the skin over the affected area rather than taken by mouth. It belongs to the NSAID (nonsteroidal anti-inflammatory drug) family.

See full Diclofenac drug information
Keep checking

Other Drugs & Grapefruit

Browse every other medication we’ve checked against Grapefruit — both the ones with a known interaction and the ones without. Select any drug for the full detail.

776Major
150Moderate
63Minor
1,840No known interaction
776 Major 150 Moderate 63 Minor 1,840 No interaction
Major

776 interactions

Showing 60 of 776 major interactions — see all 776 on the Grapefruit page.

Moderate

150 interactions

Showing 60 of 150 moderate interactions — see all 150 on the Grapefruit page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

We also checked Grapefruit against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

See the full Grapefruit interactions page
See every supplement checked against Diclofenac, 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
Grapefruit monograph › Uses, safety, and every drug interaction in one place Diclofenac supplement interactions › Every supplement checked against Diclofenac, ranked by severity Diclofenac 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 Grapefruit and Diclofenac Together: Common Questions

Can you take Grapefruit with Diclofenac?
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 Grapefruit and Diclofenac 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 Diclofenac and Grapefruit?

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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.