Drug & supplement interaction

Methoxylated Flavones + Itraconazole

Itraconazole brand names: Sporanox, Sporanox Injection, Tolsura.

Moderate Interaction
The bottom line Moderate

Itraconazole falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Methoxylated Flavones and Itraconazole

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. Itraconazole 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

P-GLYCOPROTEIN SUBSTRATES

1 of 2

Why this applies to Itraconazole

Itraconazole 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 gist for itraconazole (Sporanox, Tolsura): your body uses a kind of cellular pump called P-glycoprotein to move this antifungal around and limit how much gets absorbed. In test-tube studies, certain methoxylated flavones from citrus peel (like nobiletin and tangeretin) can block that pump. The theory is that with the pump slowed down, a bit more itraconazole could get absorbed and your blood levels could creep up.

If that happened, you might notice more of itraconazole's usual side effects, such as nausea, stomach upset, headache, or swelling. I want to be honest though: this is theoretical, based only on lab work, and a small amount of citrus in food is very unlikely to matter. Concentrated supplements are the real question. Before adding one, check with your pharmacist or doctor.

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 2

Itraconazole 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 with itraconazole (Sporanox, Tolsura). Your body relies on a liver enzyme called CYP3A4 to help break this antifungal down. Certain methoxylated flavones from citrus peel may block that enzyme in lab tests, which could let itraconazole build up a bit higher than normal. That can mean a greater chance of side effects like nausea, stomach upset, headache, or, less commonly, liver irritation or changes in heart rhythm.

I want to keep this in perspective, though. So far this is only based on test-tube data, and it hasn't actually been seen in people. Not every methoxylated flavone behaves this way either. A little citrus peel in your food is very unlikely to matter, but concentrated supplements are a bigger unknown. Run it by your pharmacist or doctor before combining them.

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

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 Itraconazole 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 Itraconazole

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 Itraconazole, 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 Itraconazole

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Itraconazole page lists 182 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 6 major · 136 moderate · 40 minor.

From our pharmacist’s overview on the Itraconazole page

“Serious fungal infections are what itraconazole (Sporanox, Tolsura) is for, and the drug travels through CYP3A4, the liver enzyme that also handles a large share of supplements. That overlap is why this list reaches 182 ingredients, and it earns genuine care; start with the six rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Itraconazole interaction page

How much people look this up

Where Methoxylated Flavones and Itraconazole 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

#1,154 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Itraconazole
Top half

#1,086 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 Itraconazole

What Is Itraconazole Used For?

Brand names: Sporanox, Sporanox Injection, Tolsura

Itraconazole capsules (including Sporanox capsules and generic itraconazole capsules) treat serious fungal infections — blastomycosis, histoplasmosis, and aspergillosis — in both people with normal immune systems and those who are immunocompromised. Capsule forms are also approved for nail fungus (onychomycosis) caused by dermatophytes in non-immunocompromised patients. Tolsura (a gelatin-coated capsule formulation) treats blastomycosis, histoplasmosis, and aspergillosis in adults, but is not approved for nail fungus and is not interchangeable with other itraconazole products.

Itraconazole oral solution is specifically approved for oropharyngeal candidiasis (thrush — a fungal infection of the mouth) and esophageal candidiasis (a fungal infection of the food pipe). Only the oral solution has been shown to work for these mouth and throat infections; capsules cannot be substituted for this use.

See full Itraconazole 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

Keep exploring
Pharmacist Counseling Corner

Taking Methoxylated Flavones and Itraconazole Together: Common Questions

Can you take Methoxylated Flavones with Itraconazole?
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 Itraconazole?
Itraconazole 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 Itraconazole 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

Still Have a Question About Itraconazole and Methoxylated Flavones?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.