Drug & supplement interaction

Methoxylated Flavones + Darolutamide

Darolutamide brand name: Nubeqa.

Moderate Interaction
The bottom line Moderate

Darolutamide 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?
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Interaction report

Methoxylated Flavones and Darolutamide

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. Darolutamide 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 Darolutamide

Darolutamide 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 Nubeqa (darolutamide): your body uses a kind of cellular bouncer called P-glycoprotein to pump some of this drug back out of your gut, which limits how much gets absorbed. Lab studies suggest the methoxylated flavones in citrus peel (like nobiletin and tangeretin) can slow that pump down. In theory, that could let a bit more darolutamide into your bloodstream, nudging up its levels.

If that happened, you might notice more of the usual darolutamide effects, such as fatigue, aches, or rash. But honestly, this is theoretical, based only on test-tube work, and a slice of orange or a normal diet is very unlikely to matter. Concentrated supplements are the bigger question mark, so just run them past your pharmacist or oncologist before starting.

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

Darolutamide 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 Nubeqa (darolutamide): your liver uses an enzyme called CYP3A4 to help break it down and clear it. Some methoxylated flavones from citrus peel may slow that enzyme down in the test tube. If that happened in your body, darolutamide could build up a bit more than expected, which in theory could mean more of its usual side effects like fatigue, achy joints, rash, or higher blood pressure.

I want to keep this in perspective, though. This warning comes only from lab studies, not from real people, and it doesn't happen with every flavone in this family. Darolutamide is not a prodrug, so the concern is too much, not too little. Before adding a concentrated supplement, run it by your oncology team or pharmacist 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

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 Darolutamide 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 Darolutamide

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Darolutamide page lists 144 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 103 moderate · 38 minor.

From our pharmacist’s overview on the Darolutamide page

“Darolutamide (Nubeqa) treats prostate cancer, and supplements deserve real caution alongside it, because most of those listed here can change how much of the drug stays in your blood. Nearly all act on CYP3A4, the liver enzyme that breaks darolutamide down, or on the transport proteins that move it through cells.”

Reviewed by 2 · Jul 18, 2026

Open the Darolutamide interaction page

How much people look this up

Where Methoxylated Flavones and Darolutamide 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

#1,066 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Darolutamide
Top half

#853 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 Darolutamide

What Is Darolutamide Used For?

Brand name: Nubeqa

Nubeqa (darolutamide) tablets are approved for adult men with two forms of advanced prostate cancer. The first is non-metastatic castration-resistant prostate cancer (nmCRPC) — cancer that keeps growing despite hormone-lowering therapy and has not yet spread to other parts of the body. The second is metastatic castration-sensitive prostate cancer (mCSPC) — cancer that has spread but still responds to hormone-lowering treatment.

For mCSPC, Nubeqa can be used alone or in combination with docetaxel (a chemotherapy medicine). In all cases, patients also receive a gonadotropin-releasing hormone (GnRH) agonist or antagonist — a medicine that lowers testosterone — or have already had surgery to remove the testicles.

See full Darolutamide 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 Darolutamide Together: Common Questions

Can you take Methoxylated Flavones with Darolutamide?
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 Darolutamide?
Darolutamide 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 Darolutamide 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.