Drug & supplement interaction

Grapefruit + Agomelatine

Agomelatine brand name: Valdoxan.

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

Agomelatine falls into 3 drug categories that Grapefruit can interact with; the most serious is rated moderate. Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C19.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Agomelatine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Grapefruit interacts with whole categories of medication. Agomelatine falls into 3 of those categories, so it can interact with Grapefruit in 3 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) SUBSTRATES

1 of 3

Why this applies to Agomelatine

Agomelatine falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Grapefruit interacts with.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C19.
In vitro research suggests that grapefruit juice might inhibit CYP2C19 enzymes. Also, a small clinical study shows that taking grapefruit juice with clopidogrel, an antiplatelet prodrug that is metabolized primarily by CYP2C19, decreases plasma levels of the active metabolite and impairs the antiplatelet effect of clopidogrel. This effect is likely due to grapefruit-induced inhibition of CYP2C19.
Severity Moderate Likelihood Possible Evidence B

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

Let's talk about pairing grapefruit with agomelatine (Valdoxan), your antidepressant. Grapefruit can slow down certain liver enzymes that help break this medicine down. Agomelatine is mainly cleared by a different enzyme (CYP1A2), but our file flags it as a CYP2C19 substrate too, and grapefruit may block that pathway. Importantly, agomelatine is not a prodrug, so slowing its breakdown would tend to let more of it build up in your body.

In real terms, higher levels could mean more drowsiness, dizziness, headache, or nausea. This is mostly theoretical and based on lab work, so don't panic, but please check with your pharmacist or doctor before drinking grapefruit juice regularly. They can confirm what's safe for you.

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
  2. Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman JT, Niemi M. Grapefruit juice inhibits the metabolic activation of clopidogrel. Clin Pharmacol Ther. 2014 Mar;95(3):307-13. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Agomelatine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP1A2.
In vitro research suggests that grapefruit juice might inhibit CYP1A2 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 basic idea with agomelatine (Valdoxan): your body relies heavily on an enzyme called CYP1A2 to break this drug down. Grapefruit may slow that enzyme down a bit, and since agomelatine works as-is (it's not a prodrug that needs activating), slowing its breakdown could let more of it build up. In theory, that might mean stronger effects or more side effects like drowsiness, dizziness, headache, or nausea.

Now, the honest part: this concern comes only from lab (test-tube) studies, and it hasn't actually been seen in real people. So I wouldn't lose sleep over an occasional grapefruit. Still, agomelatine already needs liver monitoring, so if you enjoy grapefruit regularly, mention it to your pharmacist or doctor first.

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
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Agomelatine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

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 short version on grapefruit and agomelatine (Valdoxan). Grapefruit can mildly slow down certain liver enzymes that help your body process this medicine. In theory, that could let a bit more agomelatine build up than usual, which might nudge up side effects like daytime drowsiness, dizziness, headache, or stomach upset. Agomelatine is an active drug, not a prodrug, so more in your system means a stronger effect, not a weaker one.

The good news: this particular concern comes only from lab studies, not from real patients, so the actual risk looks low. Still, agomelatine already needs liver monitoring, so it's worth a quick chat with your pharmacist or doctor before making grapefruit a daily habit.

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 Agomelatine one above is among 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. Agomelatine)
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 Agomelatine

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 Agomelatine, 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 Agomelatine

This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Agomelatine page lists 135 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (moderate), African Wild Potato (moderate), Artichoke (moderate) and Ashitaba (moderate).

By severity: 1 major · 94 moderate · 40 minor.

Open the Agomelatine 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 Agomelatine 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 Agomelatine 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 Agomelatine
Top half

#751 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
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 Agomelatine, 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 Agomelatine supplement interactions › Every supplement checked against Agomelatine, 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 Grapefruit and Agomelatine Together: Common Questions

Can you take Grapefruit with Agomelatine?
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 3 interactions listed for Grapefruit and Agomelatine?
Agomelatine belongs to more than one drug category, and Grapefruit 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 Grapefruit and Agomelatine 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 Agomelatine 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.