Drug & supplement interaction

Methoxylated Flavones + Simvastatin

Simvastatin brand name: Zocor.

Moderate Interaction
The bottom line Moderate

Simvastatin 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

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 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

Simvastatin 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 short version: your body relies on an enzyme called CYP3A4 to break down simvastatin and keep its levels in check. In test-tube studies, certain methoxylated flavones from citrus peel appear to slow that enzyme down. If that happened in people, simvastatin could build up higher than expected, and that nudges up the risk of its known side effects, mainly muscle aches, weakness, and (rarely) more serious muscle breakdown that can stress the kidneys.

The honest part: this is only lab and animal data, and it hasn't actually been seen in humans, so it's theoretical right now. Not every methoxylated flavone does this either. Still, since simvastatin is sensitive to grapefruit-type interactions, I'd run any concentrated citrus-peel supplement past your pharmacist or doctor first.

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)

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Simvastatin 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 gist for simvastatin (Zocor). Your gut uses transporters called OATPs to help shuttle some drugs into the bloodstream, and to move statins into the liver where they do their cholesterol-lowering work. In lab dish studies, methoxylated flavones from citrus peel can block these OATP transporters. In theory, that could lower how much simvastatin gets absorbed and into the liver, which might mean a bit less cholesterol-lowering benefit.

I want to be honest, though: this is based only on test-tube data and has never actually been shown to happen in people. The flavones in a normal citrus peel garnish are very unlikely to matter. A concentrated supplement is more of a question mark. Before adding one, just run it past your pharmacist or doctor so they can keep an eye on your cholesterol numbers.

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 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.

From our Q&A

Questions About Methoxylated Flavones or Simvastatin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Methoxylated Flavones or Simvastatin, 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 Simvastatin

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Simvastatin page lists 183 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 · 139 moderate · 36 minor.

Open the Simvastatin interaction page

How much people look this up

Where Methoxylated Flavones and Simvastatin 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

#1,124 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Simvastatin
Top 25%

#573 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 Simvastatin

What Is Simvastatin Used For?

Brand name: Zocor

Simvastatin tablets are used alongside a cholesterol-lowering diet to treat high LDL cholesterol (bad cholesterol), high triglycerides, and certain inherited cholesterol disorders, including heterozygous familial hypercholesterolemia (HeFH) in adults and children aged 10 and older, and homozygous familial hypercholesterolemia (HoFH) in adults.

In adults who already have coronary heart disease, cerebrovascular disease, peripheral vascular disease, or diabetes and are at high risk for heart events, simvastatin is also used to reduce the risk of death from heart disease, non-fatal heart attack, stroke, and the need for procedures to open blocked arteries. Zocor is one brand-name product containing simvastatin and carries these same indications.

See full Simvastatin 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
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
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 Simvastatin Together: Common Questions

Can you take Methoxylated Flavones with Simvastatin?
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?
Simvastatin 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 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.