Drug & supplement interaction

Methoxylated Flavones + Esomeprazole, Naproxen

Esomeprazole, Naproxen brand name: Vimovo.

Moderate Interaction
The bottom line Moderate

Esomeprazole, Naproxen falls into 3 drug categories that Methoxylated Flavones can interact with; the most serious is rated moderate. Some in vitro evidence suggests that methoxylated flavones might induce CYP1A2, possibly by increasing gene transcription.

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

Methoxylated Flavones and Esomeprazole, Naproxen

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

Why Are There 3 Interactions?

Methoxylated Flavones interacts with whole categories of medication. Esomeprazole, Naproxen falls into 3 of those categories, so it can interact with Methoxylated Flavones 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 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Esomeprazole, Naproxen

Esomeprazole, Naproxen falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Methoxylated Flavones interacts with.

Some in vitro evidence suggests that methoxylated flavones might induce CYP1A2, possibly by increasing gene transcription. However, other in vitro research has not shown this effect. So far this interaction has not been reported in humans. Theoretically, concurrent use of methoxylated flavones and drugs metabolized by CYP1A2 might increase drug metabolism, decrease serum levels, and reduce effectiveness.
Some drugs metabolized by CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), Pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline (Slo-bid, Theo-Dur, others), zileuton (Zyflo), Zolmitriptan (Zomig), 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

Vimovo is a combination of esomeprazole (a stomach acid reducer) and naproxen (an anti-inflammatory pain reliever). The concern here is that methoxylated flavones from citrus peel might speed up a liver enzyme called CYP1A2. If a drug is cleared faster, its blood levels could drop and it may not work as well. In theory, that could mean a bit less heartburn protection or less pain and inflammation relief.

Honestly, I wouldn't lose sleep over this one. The evidence is purely from lab dishes, lab results have even conflicted, and nothing like this has been seen in real people. Neither esomeprazole nor naproxen is a prodrug, and CYP1A2 isn't a major route for clearing them. Food amounts of citrus are a non-issue. If you take concentrated supplements regularly, just mention it to your pharmacist.

References
  1. Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000;52:673-751. DOI
  2. Li Y, Ning J, Wang Y, et al. Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Esomeprazole, Naproxen also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

In vitro evidence suggests that methoxylated flavones might inhibit cytochrome P450 3A4 (CYP3A4). This effect seems to be structure-dependent, and does not occur with all methoxylated flavones. So far this interaction has not been reported in humans. Theoretically, concurrent use of certain methoxylated flavones with drugs metabolized by CYP3A4 might result in increased drug levels and an increased risk for adverse effects.
Some drugs metabolized by CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), Pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline (Slo-bid, Theo-Dur, others), zileuton (Zyflo), Zolmitriptan (Zomig), 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

Vimovo combines two medicines: esomeprazole (an acid-reducer) and naproxen (an anti-inflammatory pain reliever). The concern here is that certain methoxylated flavones, like those found in citrus peel, may block the CYP3A4 enzyme in lab testing. Since esomeprazole is partly cleared by this enzyme, slowing it down could let levels build up slightly, possibly nudging up side effects like headache or stomach upset.

Here's the honest part: this is only seen in test-tube studies, and not all of these flavones cause it. It has never been reported in real people. Everyday citrus in your diet is very unlikely to matter. If you're considering a concentrated supplement, just run it by your pharmacist or doctor first to be safe.

References
  1. Li Y, Ning J, Wang Y, et al. Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 3

Esomeprazole, Naproxen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

In vitro evidence suggests that some methoxylated flavones have antiplatelet effects. Theoretically, methoxylated flavones might additive effects when used with anticoagulant or antiplatelet drugs.
Some anticoagulant or antiplatelet drugs include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), 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

Vimovo combines naproxen (an NSAID pain reliever) with esomeprazole (a stomach-acid blocker added to protect your gut). The naproxen part already nudges your platelets to clot a little less, which is why NSAIDs can sometimes increase bruising or bleeding. Methoxylated flavones from citrus peel have shown a mild platelet-slowing effect too, but only in lab dishes, not in real people.

So in theory, stacking them could add up and raise your chance of easy bruising, nosebleeds, or stomach irritation and bleeding. Honestly, this is a weak, theoretical concern, and everyday citrus in food won't be an issue. Concentrated supplement doses are the bigger question mark. If you're considering one, please run it past your pharmacist or doctor first.

References
  1. Robbins RC. Effect of methoxylated flavones on erythrocyte aggregation and sedimentation in blood of normal subjects: Evidence of a dietary role for flavonoids. Internat J Vit Nutr Res 1973;43:494-503.
  2. Robbins RC. In vitro effects of penta-, hexa-, and hepta-methoxylated flavones on aggregation of cells in blood from hospitalized patients. J Clin Pharmacol 1973;13:271-5. 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

Methoxylated Flavones Also Interacts With Other Medications

Methoxylated Flavones has 891 moderate known drug interactions in our database — the Esomeprazole, Naproxen 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 Methoxylated Flavones

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

Everything else you take

See Every Supplement That Interacts With Esomeprazole, Naproxen

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Esomeprazole, Naproxen page lists 348 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 Grapefruit (major).

By severity: 9 major · 283 moderate · 56 minor.

From our pharmacist’s overview on the Esomeprazole, Naproxen page

“Bleeding risk is the thread running through nearly this whole page. Vimovo pairs naproxen, an anti-inflammatory that already makes stomach bleeding more likely, with esomeprazole on board to shield the gut, and most of the supplements flagged here could push that bleeding risk higher still.”

Reviewed by 2 · Jul 18, 2026

Open the Esomeprazole, Naproxen interaction page

How much people look this up

Where Methoxylated Flavones and Esomeprazole, Naproxen 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 Methoxylated Flavones
Steady interest

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

29 days ago today
Medication Esomeprazole, Naproxen
Steady interest

#1,706 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 Methoxylated Flavones

What is Methoxylated Flavones?

  • Antioxidant support
  • Circulation and blood vessel health
  • Anti-inflammatory support
  • Skin and aging support
  • General 'metabolism' or wellness blends

Methoxylated flavones (often called polymethoxyflavones) are a group of plant compounds, found mainly in citrus peel, that include substances like nobiletin and tangeretin. Lab and animal studies suggest possible antioxidant and anti-inflammatory effects, but solid human research is very limited, so their real-world benefits are unproven. Talk with a pharmacist or doctor before using them, especially if you take medicines or are pregnant or breastfeeding.

Read the full Methoxylated Flavones monograph & all interactions
Keep checking

Other Drugs & Methoxylated Flavones

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

0Major
891Moderate
0Minor
1,938No known interaction
Moderate

891 interactions

Showing 60 of 891 moderate interactions — see all 891 on the Methoxylated Flavones page.

No interaction 1,938 drugs checked — show the list

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

Showing the 60 most looked-up of 1,938 medications checked with no known interaction — see the full Methoxylated Flavones 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 Methoxylated Flavones and Esomeprazole, Naproxen Together: Common Questions

Can you take Methoxylated Flavones with Esomeprazole, Naproxen?
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 Methoxylated Flavones and Esomeprazole, Naproxen?
Esomeprazole, Naproxen belongs to more than one drug category, and Methoxylated Flavones 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 Methoxylated Flavones and Esomeprazole, Naproxen 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.