Drug & supplement interaction

Diosmin + Nintedanib Esylate

Nintedanib Esylate brand name: Ofev.

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

Nintedanib Esylate falls into 3 drug categories that Diosmin can interact with; the most serious is rated moderate. Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Diosmin and Nintedanib Esylate

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Diosmin interacts with whole categories of medication. Nintedanib Esylate falls into 3 of those categories, so it can interact with Diosmin in 3 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

1 of 3

Why this applies to Nintedanib Esylate

Nintedanib Esylate falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Diosmin interacts with.

Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.
Laboratory research is conflicting with respect to the effects of diosmin on CYP3A4. Some research suggests that diosmin does not affect CYP3A4 activity. However, other research suggests that diosmin alters the metabolism of carbamazepine, a CYP3A4 substrate. Laboratory and animal research show that oral administration of diosmin for 7 days prior to oral administration of carbamazepine increases plasma concentrations of carbamazepine, decreases the clearance of carbamazepine, and decreases the formation of carbamazepine's active metabolite. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42%. It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting CYP3A4. Diosmetin, a metabolite of diosmin, may also inhibit CYP3A4.
Severity Moderate Likelihood Possible Evidence B

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 Ofev (nintedanib) and diosmin. Nintedanib is partly handled by an enzyme called CYP3A4. Diosmin may slow that enzyme down, and if it does, your body could clear nintedanib a little less efficiently, letting levels creep up. Nintedanib isn't a prodrug, so more drug in your system means a bigger chance of its usual side effects, things like diarrhea, nausea, belly pain, poor appetite, and liver enzyme changes your doctor watches on bloodwork.

That said, the evidence here is shaky and mostly theoretical, and some lab studies show no real effect on CYP3A4. So I wouldn't panic. Just loop in your pharmacist or doctor before adding diosmin, since they may want to keep an eye on how you're tolerating Ofev.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bedada SK, Neerati P. Modulation of CYP3A enzyme activity by diosmin and its consequence on carbamazepine pharmacokinetics in rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(2):115-21. PubMed
  2. Burkina V, Zlabek V, Halsne R, Ropstad E, Zamaratskaia G. In vitro effects of the citrus flavonoids diosmin, naringenin and naringin on the hepatic drug-metabolizing CYP3A enzyme in human, pig, mouse and fish. Biochem Pharmacol. 2016;110-111:109-16 PubMed
  3. Bedada SK, Boga PK. Influence of diosmin on the metabolism and disposition of carbamazepine in healthy subjects. Xenobiotica. 2017;47(10):879-84. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 3

Nintedanib Esylate also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, diosmin might increase levels of drugs that are substrates of P-glycoprotein (P-gp).
Preliminary laboratory research suggests that diosmin inhibits P-gp. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of fexofenadine 120 mg increases blood levels of fexofenadine, a P-gp substrate, by approximately 49% and decreases the apparent oral clearance of fexofenadine by 41%. The time taken to reach maximum plasma concentration, the half-life, and the apparent renal clearance of fexofenadine are not affected. For this reason, it is speculated that diosmin inhibits P-gp in the intestine, but not in the kidney or liver.
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 Ofev (nintedanib). Your body partly limits how much of this drug gets absorbed using a kind of cellular gatekeeper called P-glycoprotein, or P-gp. Diosmin appears to slow that gatekeeper down in the gut, at least in early lab and small human studies. If the gate is held open, a bit more nintedanib could slip into your bloodstream.

For you, that could mean more of nintedanib's usual side effects, mainly diarrhea, nausea, stomach upset, loss of appetite, and possibly liver enzyme changes. To be clear, this is theoretical and based on weak evidence, so it isn't a sure thing. Still, since nintedanib can already be hard on the gut, it's worth a quick chat with your pharmacist or doctor before adding diosmin.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yoo HH, Lee M, Chung HJ, Lee SK, Kim DH. Effects of diosmin, a flavonoid glycoside in citrus fruits, on P-glycoprotein-mediated drug efflux in human intestinal Caco-2 cells. J Agric Food Chem. 2007 Sep 5;55(18):7620-5. PubMed
  2. Bedada SK, Boga PK, Kotakonda HK. The effect of diosmin on the pharmacokinetics of fexofenadine in healthy human volunteers. Xenobiotica. 2017;47(3):230-35. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 3

Nintedanib Esylate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, diosmin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
A case of spontaneous intraventricular hemorrhage has been reported for a 77-year-old female after 6 weeks of warfarin therapy, despite an international normalized ratio (INR) of only 1.8. The patient had also been taking aspirin and diosmin for several years. Experts speculate that chronic intake of diosmin predisposed the patient to spontaneous intraventricular hemorrhage by inducing chronic microcirculatory hypertension and inhibiting platelet aggregation. The presence of aspirin was also thought to play a role in this event.
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: nintedanib (Ofev) can raise your bleeding risk on its own, and diosmin may have a mild blood-thinning effect of its own too. Put them together and, in theory, those small effects could add up. With Ofev specifically, people sometimes notice things like easy bruising, nosebleeds, bleeding gums, or stomach upset that can include bleeding. So this is mostly about not stacking bleeding risks.

I want to be honest about the strength of this concern. It's largely theoretical and comes from a single case report involving warfarin and aspirin, not Ofev. That said, I'd still mention it to your pharmacist or doctor before adding diosmin, and let them know right away if you see unusual bleeding or bruising. Please don't stop or change your Ofev on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kumar RM, Van Gompel JJ, Bower R, Rabinstein AA. Spontaneous intraventricular hemorrhage associated with prolonged diosmin therapy. Neurocrit Care. 2011 Jun;14(3):438-40. 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

Diosmin Also Interacts With Other Medications

Diosmin has 883 moderate known drug interactions in our database — the Nintedanib Esylate one above is among them. If you take anything else, check it against the full list below.

Moderate 883 No known interaction 1,947 (incl. Nintedanib Esylate)
Taking anything else?

Check Another of Your Medications Against Diosmin

Covers the 2,830 medications we’ve checked against Diosmin. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Nintedanib Esylate

This page covers Diosmin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nintedanib Esylate page lists 285 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Danshen (major), Grapefruit (major), Piracetam (major) and St. John's Wort (major).

By severity: 5 major · 240 moderate · 40 minor.

From our pharmacist’s overview on the Nintedanib Esylate page

“You take Ofev (nintedanib) to slow lung scarring, and this page deserves a careful read before any supplement joins it. Of the 285 ingredients here, the biggest cluster, over 200, can add to bleeding risk, a real concern since nintedanib itself can make you bleed more easily.”

Reviewed by 2 · Jul 18, 2026

Open the Nintedanib Esylate interaction page

One more smart check

Taking Diosmin as Part of a Dietary Supplement Product? Check It for Interactions

We hold 121 real supplement products containing Diosmin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Diosmin. Your product may carry other ingredients that interact with Nintedanib Esylate too, on top of Diosmin — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Diosmin and Nintedanib Esylate 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 Diosmin
Top half

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

29 days ago today
Medication Nintedanib Esylate
Steady interest

#1,603 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 Diosmin

What is Diosmin?

  • Chronic venous insufficiency
  • Hemorrhoids
  • Leg swelling and heaviness
  • Varicose veins
  • Spider veins

Diosmin is a citrus-derived flavonoid most often used for vein-related problems such as chronic venous insufficiency and hemorrhoids, and it is usually combined with a related flavonoid called hesperidin. Some studies suggest it may help relieve leg swelling and hemorrhoid symptoms, but quality varies. Talk to your pharmacist or doctor before starting it, especially if you are pregnant or breastfeeding.

Read the full Diosmin monograph & all interactions
Medication

About Nintedanib

What Is Nintedanib Used For?

Brand name: Ofev

Nintedanib capsules are approved for adults with idiopathic pulmonary fibrosis (IPF) — a chronic, progressive scarring of the lungs — and for adults with chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype, meaning fibrosing lung diseases that continue to worsen over time despite treatment.

Nintedanib capsules (including Ofev) are also indicated to slow the rate of decline in lung function in adults with systemic sclerosis-associated interstitial lung disease (SSc-ILD), a lung complication of the autoimmune condition systemic sclerosis (scleroderma). Note that the Nintedanib esylate capsule product is approved for IPF and chronic fibrosing ILDs with a progressive phenotype, but SSc-ILD approval is carried by Ofev and other nintedanib capsule products — always confirm with your prescriber which product you have been prescribed.

See full Nintedanib drug information
Keep checking

Other Drugs & Diosmin

Browse every other medication we’ve checked against Diosmin — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
883Moderate
0Minor
1,946No known interaction
883 Moderate 1,946 No interaction
Moderate

883 interactions

Showing 60 of 883 moderate interactions — see all 883 on the Diosmin page.

No interaction 1,946 drugs checked — show the list

We also checked Diosmin against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,946 medications checked with no known interaction — see the full Diosmin list.

See the full Diosmin interactions page
See every supplement checked against Nintedanib Esylate, 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
Diosmin monograph › Uses, safety, and every drug interaction in one place Nintedanib Esylate supplement interactions › Every supplement checked against Nintedanib Esylate, ranked by severity Nintedanib 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 Diosmin and Nintedanib Esylate Together: Common Questions

Can you take Diosmin with Nintedanib Esylate?
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 3 interactions listed for Diosmin and Nintedanib Esylate?
Nintedanib Esylate belongs to more than one drug category, and Diosmin 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 Diosmin and Nintedanib Esylate 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 Nintedanib Esylate and Diosmin?

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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.