Drug & supplement interaction

Methoxylated Flavones + simvastatin/ezetimibe

simvastatin/ezetimibe brand name: Vytorin.

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

simvastatin/ezetimibe falls into 2 drug categories that Methoxylated Flavones can interact with; the most serious is rated moderate. In vitro evidence suggests that methoxylated flavones might inhibit cytochrome P450 3A4 (CYP3A4).

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Methoxylated Flavones and simvastatin/ezetimibe

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Methoxylated Flavones interacts with whole categories of medication. simvastatin/ezetimibe falls into 2 of those categories, so it can interact with Methoxylated Flavones in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

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Why this applies to simvastatin/ezetimibe

simvastatin/ezetimibe falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Methoxylated Flavones interacts with.

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 with Vytorin: the simvastatin part is cleared by a liver enzyme called CYP3A4. Some methoxylated flavones from citrus peel can slow that enzyme down in the test tube. If that happened in your body, simvastatin could build up a bit, which raises the chance of statin side effects like muscle aches, weakness, or, rarely, more serious muscle breakdown. The ezetimibe piece isn't really affected this way.

The important thing is that this is theoretical. It comes from lab studies only and hasn't been seen in real people, and not every flavone does it. A bit of citrus in your diet is very unlikely to matter. Concentrated supplements are the bigger question mark, so check with your pharmacist before adding one.

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

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

2 of 2

simvastatin/ezetimibe also falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP).

In vitro, methoxylated flavones inhibit organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. This may reduce the bioavailability of oral drugs that are substrates of OATP. However, 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 simple version. Vytorin combines simvastatin and ezetimibe to lower your cholesterol. Both of these rely on certain transporter proteins (called OATP) to get into your liver, which is exactly where they need to work. In test-tube studies, these citrus peel flavones blocked those transporters. If that happened in the body, less of your medicine might reach the liver, so it could become less effective at lowering your LDL.

I want to be straight with you, though: this is only lab data, and it has never actually been seen in people taking these drugs. Everyday citrus or a glass of juice isn't the concern, concentrated supplement capsules are the bigger question mark. Before adding a flavone supplement, just run it by your pharmacist or doctor so they can keep an eye on your cholesterol numbers.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bajraktari-Sylejmani G, Weiss J. Potential risk of food-drug interactions: Citrus polymethoxyflavones and flavanones as inhibitors of the organic anion transporting polypeptides (OATP) 1B1, 1B3, and 2B1. Eur J Drug Metab Pharmacokinet. 2020;45(6):809-815. 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 simvastatin/ezetimibe one above is among them. If you take anything else, check it against the full list below.

Moderate 891 No known interaction 1,939 (incl. simvastatin/ezetimibe)
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 simvastatin/ezetimibe

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the simvastatin/ezetimibe page lists 184 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 8 major · 140 moderate · 36 minor.

From our pharmacist’s overview on the simvastatin/ezetimibe page

“Anyone taking simvastatin with ezetimibe (Vytorin) should treat this list with real care, since eight of its 184 entries are rated major and some involve everyday foods. Most of the list, 121 ingredients, runs through the CYP3A4 enzyme that clears simvastatin, and the traffic goes both ways.”

Reviewed by 2 · Jul 18, 2026

Open the simvastatin/ezetimibe interaction page

How much people look this up

Where Methoxylated Flavones and simvastatin/ezetimibe 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

#1,064 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication simvastatin/ezetimibe
Top 10%

#212 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
891 Moderate 1,938 No 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.

See the full Methoxylated Flavones interactions page
See every supplement checked against simvastatin/ezetimibe, 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 simvastatin/ezetimibe supplement interactions › Every supplement checked against simvastatin/ezetimibe, 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 Methoxylated Flavones and simvastatin/ezetimibe Together: Common Questions

Can you take Methoxylated Flavones with simvastatin/ezetimibe?
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 2 interactions listed for Methoxylated Flavones and simvastatin/ezetimibe?
simvastatin/ezetimibe 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 simvastatin/ezetimibe 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.