Drug & supplement interaction

Methoxylated Flavones + Bosentan

Bosentan brand name: Tracleer.

Moderate Interaction
The bottom line Moderate

Bosentan 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 Bosentan

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. Bosentan 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 Bosentan

Bosentan 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 gist with bosentan (Tracleer): your liver uses an enzyme called CYP3A4 to help clear it out of your body. In lab (test tube) studies, certain methoxylated flavones from citrus peel appear to slow that enzyme down. If that happened in real life, bosentan could build up a bit higher than expected, which might mean more of its usual side effects like headache, flushing, swelling in the legs or feet, low blood pressure, or strain on the liver.

I want to be straight with you, though: this is only seen in lab studies, not in actual people, and it doesn't happen with every flavone. So it's more of a theoretical caution than a proven problem. Still, since bosentan needs regular liver monitoring, it's worth running any concentrated citrus-peel supplement past your pharmacist or doctor first. Normal amounts of citrus in food aren't a concern.

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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Bosentan 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 is the gist for bosentan (Tracleer). Your body relies on transporter proteins called OATP to help move bosentan from your gut into your bloodstream. In test-tube studies, methoxylated flavones from citrus peel can block those same OATP transporters. In theory, that could mean less bosentan actually gets absorbed, which might make it work less well for keeping your lung blood pressure under control.

I want to be honest about how soft this evidence is. It comes only from lab dishes, not from real people, so we truly don't know if it matters in everyday life. A bit of citrus in your food is very unlikely to be an issue. Concentrated flavone supplements are the bigger question mark. Since bosentan is an important medicine, just run any supplement past your pharmacist or doctor first.

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 Bosentan 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 Bosentan

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Bosentan page lists 266 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), Apple (major) and Beer (major).

By severity: 11 major · 216 moderate · 39 minor.

Open the Bosentan interaction page

How much people look this up

Where Methoxylated Flavones and Bosentan 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

#1,148 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Bosentan
Top half

#1,100 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 Bosentan

What Is Bosentan Used For?

Brand name: Tracleer

Bosentan is used to treat pulmonary arterial hypertension (PAH) — high blood pressure in the arteries of the lungs. In adults, it helps improve the ability to exercise and slows how quickly the disease gets worse.

In children aged 3 years and older with idiopathic (no known cause) or congenital (present from birth) PAH, bosentan is used to lower resistance in the lung blood vessels, which is expected to improve exercise ability. Tracleer is one brand approved for both adults and pediatric patients with PAH.

See full Bosentan 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 Bosentan Together: Common Questions

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