Drug & supplement interaction

Methoxylated Flavones + Macitentan

Macitentan brand name: Opsumit.

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

Methoxylated Flavones has a moderate interaction with Macitentan. In vitro evidence suggests that methoxylated flavones might inhibit cytochrome P450 3A4 (CYP3A4).

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Methoxylated Flavones and Macitentan

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Macitentan

Macitentan 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

Your body relies on a liver enzyme called CYP3A4 to break down and clear macitentan (Opsumit). Certain methoxylated flavones from citrus peel may slow that enzyme down, at least in test-tube studies. If they did the same thing in people, macitentan could clear more slowly and build up a bit, which might mean more of its usual side effects, like a stuffy or runny nose, headache, low blood pressure, fluid retention with swelling, or a drop in red blood cells.

Here's the reassuring part: this is only seen in lab work so far, not in real patients, and it does not happen with every flavone. So I wouldn't lose sleep over it, but since macitentan is a serious medication, it's worth a quick chat with your pharmacist or doctor before adding a concentrated supplement.

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 892 moderate known drug interactions in our database — the Macitentan one above is one of them. If you take anything else, check it against the full list below.

Moderate 892 No known interaction 1,938 (incl. Macitentan)
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 Macitentan

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Macitentan page lists 253 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 · 205 moderate · 39 minor.

From our pharmacist’s overview on the Macitentan page

“If you take macitentan (Opsumit) for pulmonary arterial hypertension, study this page rather than skim it. It lists 253 supplement and herbal ingredients, nine rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Macitentan interaction page

How much people look this up

Where Methoxylated Flavones and Macitentan 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

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

29 days ago today
Medication Macitentan
Top 25%

#507 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 Macitentan

What Is Macitentan Used For?

Brand name: Opsumit

Macitentan tablets — sold under the brand name Opsumit — are used to treat pulmonary arterial hypertension (PAH, WHO Group I), a type of high blood pressure in the arteries of the lungs. The goal is to slow the disease from getting worse and to lower the chance of being hospitalized because of PAH.

In the key clinical study, macitentan was used in adults with mainly moderate-to-severe PAH symptoms. Patients had PAH caused by unknown or inherited causes, connective tissue disorders, or congenital heart disease with repaired shunts.

See full Macitentan 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
892Moderate
0Minor
1,937No known interaction
892 Moderate 1,937 No interaction
Moderate

892 interactions

Showing 60 of 892 moderate interactions — see all 892 on the Methoxylated Flavones page.

No interaction 1,937 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 1,937 medications checked with no known interaction — see the full Methoxylated Flavones list.

See the full Methoxylated Flavones interactions page
See every supplement checked against Macitentan, 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 Macitentan supplement interactions › Every supplement checked against Macitentan, ranked by severity Macitentan 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 Macitentan Together: Common Questions

Can you take Methoxylated Flavones with Macitentan?
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.
How serious is the Methoxylated Flavones and Macitentan 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 Macitentan and Methoxylated Flavones?

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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.