Drug & supplement interaction

Methoxylated Flavones + Simvastatin, Sitagliptin

Simvastatin, Sitagliptin brand name: Juvisync.

Moderate Interaction
The bottom line Moderate

Simvastatin, Sitagliptin 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, Sitagliptin

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, Sitagliptin 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, Sitagliptin

Simvastatin, Sitagliptin 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

Juvisync is a combo pill, and the part that matters here is the simvastatin. Your liver uses an enzyme called CYP3A4 to clear simvastatin out of your body. Some methoxylated flavones (citrus peel compounds like nobiletin) can slow that enzyme down in the test tube. If that happened in your body, simvastatin could build up higher than expected, which raises the odds of muscle aches, weakness, or in rare cases more serious muscle breakdown. The sitagliptin part is mostly cleared by the kidneys, so it is not really involved.

Here is the reassuring part: this is only lab-dish evidence and has never actually been reported in people, and not every flavone does it. A little citrus in your diet is unlikely to be a problem. If you want to take a concentrated supplement, just run it by 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, Sitagliptin 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

Juvisync combines two medicines: simvastatin (a cholesterol-lowering statin) and sitagliptin (a diabetes pill). The simvastatin part is the piece that relies on a liver uptake transporter called OATP1B1 to get into the liver where it does its job. In test-tube studies, methoxylated flavones from citrus peel can block these OATP transporters. In theory, that could let less simvastatin reach the liver, which might make it work a little less well at lowering your LDL.

Here's the honest part: this is lab-only evidence and has never actually been seen in people, so I wouldn't lose sleep over it. A little citrus in your diet is no concern. Concentrated supplement doses are more of an unknown. Before adding a flavone supplement, just run it by your pharmacist or doctor.

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, Sitagliptin 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 Simvastatin, Sitagliptin

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Simvastatin, Sitagliptin page lists 362 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 · 304 moderate · 50 minor.

From our pharmacist’s overview on the Simvastatin, Sitagliptin page

“Juvisync pairs simvastatin for cholesterol with sitagliptin for type 2 diabetes, and that combination carries 362 supplement interactions on file, eight rated major, so read this page with real care rather than a quick skim. Grapefruit stands out as the everyday hazard; it blocks the enzyme that clears simvastatin, raising statin level…”

Reviewed by 2 · Jul 18, 2026

Open the Simvastatin, Sitagliptin interaction page

How much people look this up

Where Methoxylated Flavones and Simvastatin, Sitagliptin 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

#1,099 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Simvastatin, Sitagliptin
Top half

#1,324 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
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, Sitagliptin Together: Common Questions

Can you take Methoxylated Flavones with Simvastatin, Sitagliptin?
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, Sitagliptin?
Simvastatin, Sitagliptin 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, Sitagliptin 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.