Drug & supplement interaction

Methoxylated Flavones + Ambrisentan

Ambrisentan brand names: Letairis, Volibris.

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

Ambrisentan 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 Ambrisentan

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. Ambrisentan 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 Ambrisentan

Ambrisentan 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 Letairis (ambrisentan). Your body uses a tiny pump called P-glycoprotein to move certain medicines around and limit how much gets absorbed. Methoxylated flavones from citrus peel (like nobiletin and tangeretin) may slow that pump down in lab tests. In theory, that could let a bit more ambrisentan into your bloodstream, which might nudge up its usual side effects, things like swelling in your legs or ankles, stuffy nose, flushing, or feeling lightheaded.

I want to be honest about the strength here: this is theoretical, based on cell studies, not real patients. Everyday citrus in food is very unlikely to matter. A concentrated supplement is the bigger question mark. Before adding one, run it past your pharmacist or doctor so they can keep an eye on you.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Ambrisentan 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

Your body clears ambrisentan partly through a liver enzyme called CYP3A4. Certain methoxylated flavones from citrus peel (like nobiletin) have, in test-tube studies, slowed this same enzyme down a bit. If that happened in real life, ambrisentan could clear a little more slowly and build up, which might mean more of its usual side effects, such as swelling in your legs or ankles, nasal congestion, flushing, headache, or a drop in red blood cells (anemia).

Here's the reassuring part: this is only lab-dish evidence, it doesn't happen with every flavone, and it has never actually been reported in people. Everyday citrus in food is very unlikely to matter. A concentrated supplement is a different story, so check with your pharmacist or doctor before adding one. Don't change your ambrisentan on your own.

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

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 Ambrisentan 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. Ambrisentan)
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 Ambrisentan

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ambrisentan page lists 256 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Beer (major) and Grapefruit (major).

By severity: 9 major · 210 moderate · 37 minor.

Open the Ambrisentan interaction page

How much people look this up

Where Methoxylated Flavones and Ambrisentan 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
Top half

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

29 days ago today
Medication Ambrisentan
Steady interest

#1,552 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 Ambrisentan

What Is Ambrisentan Used For?

Brand names: Letairis, Volibris

Ambrisentan tablets and Letairis tablets are both used to treat pulmonary arterial hypertension (PAH, WHO Group 1) — a condition where the blood pressure in the arteries leading to the lungs is dangerously high. Both are approved to help adults exercise better and slow the worsening of PAH.

Both ambrisentan tablets and Letairis are also approved to be used together with tadalafil (another PAH medicine) to further reduce the risk of disease progression, lower the chance of hospitalization for worsening PAH, and improve exercise ability. Most of the clinical evidence was in patients with mild-to-moderate symptoms and PAH caused by unknown or inherited causes, or PAH linked to connective tissue diseases.

See full Ambrisentan 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
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 Ambrisentan, 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 Ambrisentan supplement interactions › Every supplement checked against Ambrisentan, ranked by severity Ambrisentan drug information › The full plain-English guide to this medication 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 Ambrisentan Together: Common Questions

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