Drug & supplement interaction

Methoxylated Flavones + Nintedanib Esylate

Nintedanib Esylate brand name: Ofev.

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

Nintedanib Esylate falls into 3 drug categories that Methoxylated Flavones can interact with; the most serious is rated moderate. In vitro evidence shows that some methoxylated flavones including tangeretin, nobiletin, and heptamethoxyflavone, inhibit P-glycoprotein.

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

Methoxylated Flavones and Nintedanib Esylate

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. Nintedanib Esylate 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

P-GLYCOPROTEIN SUBSTRATES

1 of 3

Why this applies to Nintedanib Esylate

Nintedanib Esylate falls under P-GLYCOPROTEIN SUBSTRATES — the group Methoxylated Flavones interacts with.

In vitro evidence shows that some methoxylated flavones including tangeretin, nobiletin, and heptamethoxyflavone, inhibit P-glycoprotein. Theoretically, these methoxylated flavones might increase absorption and blood levels of drugs that are transported by P-glycoprotein.
Some of these drugs include some chemotherapeutic agents (daunorubicin, docetaxel, etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), protease inhibitors (amprenavir, indinavir, nelfinavir, saquinavir), H2 antagonists (cimetidine, ranitidine), some calcium channel blockers (diltiazem, verapamil), corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, 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 connection worth knowing about. Your nintedanib (Ofev) relies on a tiny cellular pump called P-glycoprotein to help move it in and out of cells. Lab studies show certain citrus-peel compounds in methoxylated flavones, like nobiletin and tangeretin, can block that pump. In theory, slowing the pump down could let more nintedanib get absorbed, nudging your blood levels higher.

If that happened, the side effects nintedanib is already known for could become more noticeable, things like diarrhea, nausea, stomach upset, poor appetite, and liver enzyme changes. I'll be honest though: this is based only on test-tube data, not real people, so it's more of a theoretical caution than a proven problem. Still, please check with your pharmacist or doctor before adding a concentrated flavone supplement. Eating normal amounts of citrus is unlikely to be an issue.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Takanaga H, Ohnishi A, Yamada S, et al. Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4. J Pharmacol Exp Ther 2000;293:230-6. DOI
  2. Feng SL, Yuan ZW, Yao XJ, et al. Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport function. Pharmacol Res 2016;110:193-204. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Nintedanib Esylate 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

Here's the gist for Ofev (nintedanib). Your body uses an enzyme called CYP3A4 as one way to clear this medicine. Certain methoxylated flavones from citrus peel may slow that enzyme down in lab tests. In theory, a slower enzyme means a bit more nintedanib hanging around, which could nudge up its usual side effects like diarrhea, nausea, stomach pain, poor appetite, or changes in your liver tests.

I want to keep this in perspective, though. This is based only on test-tube research, it doesn't happen with every flavone, and it has not been seen in real people. Everyday citrus in your diet is unlikely to be a problem. Before adding a concentrated supplement, just run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Nintedanib Esylate 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

Here's the connection worth knowing. Methoxylated flavones from citrus peel have shown a mild blood-thinning (antiplatelet) effect in lab dishes. Nintedanib itself can already nudge up your bleeding risk, since it slows the growth of new blood vessels as part of how it fights lung scarring. So the worry is that the two together might add up and make bleeding a little more likely.

In real life this could look like easier bruising, nosebleeds, bleeding gums, or, less often, more serious bleeding. I'll be straight with you though: this interaction is theoretical, based only on lab data, not on people taking both. Concentrated supplement doses are the concern, not a bit of citrus zest in your cooking. Before adding these supplements, please run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
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 892 moderate known drug interactions in our database — the Nintedanib Esylate one above is among them. If you take anything else, check it against the full list below.

Moderate 892 No known interaction 1,938 (incl. Nintedanib Esylate)
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 Nintedanib Esylate

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nintedanib Esylate page lists 285 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Danshen (major), Grapefruit (major), Piracetam (major) and St. John's Wort (major).

By severity: 5 major · 240 moderate · 40 minor.

From our pharmacist’s overview on the Nintedanib Esylate page

“You take Ofev (nintedanib) to slow lung scarring, and this page deserves a careful read before any supplement joins it. Of the 285 ingredients here, the biggest cluster, over 200, can add to bleeding risk, a real concern since nintedanib itself can make you bleed more easily.”

Reviewed by 2 · Jul 18, 2026

Open the Nintedanib Esylate interaction page

How much people look this up

Where Methoxylated Flavones and Nintedanib Esylate 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
Top half

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

29 days ago today
Medication Nintedanib Esylate
Top half

#1,127 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
Medication

About Nintedanib

What Is Nintedanib Used For?

Brand name: Ofev

Nintedanib treats certain scarring lung diseases in adults. All the supported products are indicated for idiopathic pulmonary fibrosis (IPF) and for chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype (scarring lung disease that keeps getting worse).

Ofev, nintedanib capsules (100 mg and 150 mg) and one other nintedanib capsule product are also indicated to slow the decline in lung function in systemic sclerosis-associated interstitial lung disease (SSc-ILD). The nintedanib esylate capsule label lists only IPF and progressive chronic fibrosing ILDs.

See full Nintedanib drug information
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
892Moderate
0Minor
1,937No known interaction
892 Moderate 1,937 No interaction
Moderate

892 interactions

Showing 60 of 892 moderate interactions — see all 892 on the Methoxylated Flavones page.

No interaction 1,937 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 1,937 medications checked with no known interaction — see the full Methoxylated Flavones list.

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

Can you take Methoxylated Flavones with Nintedanib Esylate?
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 Nintedanib Esylate?
Nintedanib Esylate 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 Nintedanib Esylate 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.