Drug & supplement interaction

Methoxylated Flavones + Sirolimus

Sirolimus brand name: Rapamune.

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

Sirolimus 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 Sirolimus

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. Sirolimus 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 Sirolimus

Sirolimus 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 sirolimus (Rapamune). Your body uses a transporter pump called P-glycoprotein to push some of this drug back out of your gut, which keeps levels in check. In lab studies, certain methoxylated flavones from citrus peel (like nobiletin and tangeretin) can slow that pump down. The theory is that with the pump working less, more sirolimus could get absorbed and your blood levels could creep up.

That matters because sirolimus is a narrow-therapeutic-index drug, so even small shifts can tip you toward side effects like mouth sores, swelling, high cholesterol, low blood counts, or kidney strain. Keep in mind this is theoretical, based only on lab data, and an orange isn't the same as a concentrated supplement. Please check with your transplant team before adding these.

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

Sirolimus 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 sirolimus (Rapamune). Your body relies on a liver enzyme called CYP3A4 to clear this medicine out. Certain methoxylated flavones from citrus peel may, at least in lab dishes, slow that enzyme down. If that were to happen in real life, sirolimus could build up to higher levels than your transplant team intended.

Why this matters: sirolimus is a narrow-therapeutic-index drug, so even modest level changes can tip you toward side effects like mouth sores, swelling, high cholesterol, low blood counts, or kidney issues. The good news is this is only theoretical so far, seen in test tubes and not reported in people, and a little citrus seasoning is different from a concentrated supplement. Still, because your levels are watched closely, please check with your transplant pharmacist or doctor before adding these.

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 Sirolimus 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. Sirolimus)
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 Sirolimus

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 Sirolimus, 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 Sirolimus

This page covers Methoxylated Flavones only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sirolimus page lists 188 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 Active Hexose Correlated Compound (ahcc) (moderate).

By severity: 3 major · 149 moderate · 36 minor.

From our pharmacist’s overview on the Sirolimus page

“Sirolimus (Rapamune) is the anti-rejection medicine transplant patients depend on, and it is a narrow-therapeutic-index drug, meaning small shifts in its blood level can invite rejection on one side or toxicity on the other. That is why the 188 supplements on this page deserve genuine wariness, starting with the three rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Sirolimus interaction page

How much people look this up

Where Methoxylated Flavones and Sirolimus 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 Sirolimus
Steady interest

#1,451 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 Sirolimus

What Is Sirolimus Used For?

Brand name: Rapamune

Sirolimus oral solution and tablets are used to help prevent organ rejection in kidney (renal) transplant patients aged 13 and older. They are also used to treat lymphangioleiomyomatosis (LAM) — a rare lung disease in which abnormal muscle-like cells invade lung tissue.

Fyarro (sirolimus, intravenous injection) is used to treat adults with locally advanced, unresectable, or metastatic malignant PEComa — a rare tumor that grows in soft tissue or organs. Hyftor (sirolimus topical gel) is used to treat facial angiofibroma (small benign skin growths on the face) associated with tuberous sclerosis in adults and children aged 6 and older.

See full Sirolimus 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 Sirolimus, 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 Sirolimus supplement interactions › Every supplement checked against Sirolimus, ranked by severity Sirolimus 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 Sirolimus Together: Common Questions

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