Drug & supplement interaction

Diosmin + Diclofenac Sodium, Misoprostol

Diclofenac Sodium, Misoprostol brand names: Arthrotec 50, Arthrotec 75.

Moderate Interaction
The bottom line Moderate

Diclofenac Sodium, Misoprostol falls into 3 drug categories that Diosmin can interact with; the most serious is rated moderate. Theoretically, diosmin might inhibit the metabolism of CYP2C9 substrates.

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

Diosmin and Diclofenac Sodium, Misoprostol

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. Diclofenac Sodium, Misoprostol 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 2C9 (CYP2C9) SUBSTRATES

1 of 3

Why this applies to Diclofenac Sodium, Misoprostol

Diclofenac Sodium, Misoprostol falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Diosmin interacts with.

Theoretically, diosmin might inhibit the metabolism of CYP2C9 substrates.
Diclofenac is metabolized by CYP2C9 enzymes. Clinical and laboratory research shows that diosmin inhibits the metabolism of diclofenac. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of diclofenac 100 mg increases blood levels of diclofenac and decreases diclofenac clearance.
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: the diclofenac part of Arthrotec is cleared from your body mainly by a liver enzyme called CYP2C9. Diosmin appears to slow that enzyme down a bit, so the diclofenac can hang around longer and rise to higher levels than usual. In plain terms, you could feel more of the drug's effects, including the typical NSAID side effects like stomach upset, heartburn, fluid retention, raised blood pressure, or a higher risk of stomach irritation and bleeding.

The good news is this is mostly a theoretical concern, though one small human study did see diclofenac levels go up. The misoprostol piece isn't really involved here. I wouldn't panic, but it's worth a quick chat with your pharmacist or doctor before combining them, especially if you have stomach, kidney, or blood pressure issues.

References
  1. Rajnarayana K, Venkatesham A, Krishna DR. Bioavailability of diclofenac sodium after pretreatment with diosmin in healthy volunteers. Drug Metabol Drug Interact. 2007;22(2-3):165-74. PubMed
  2. Poór M, Boda G, Mohos V, et al. Pharmacokinetic interaction of diosmetin and silibinin with other drugs: Inhibition of CYP2C9-mediated biotransformation and displacement from serum albumin. Biomed Pharmacother. 2018;102:912-921. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 3

Diclofenac Sodium, Misoprostol 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

Arthrotec combines diclofenac, an anti-inflammatory pain reliever, with misoprostol to protect the stomach. The diclofenac part already nudges your bleeding risk up a bit, because NSAIDs irritate the stomach lining and make platelets (the cells that help your blood clot) a little less sticky. Diosmin may add to that effect, since it's thought to mildly affect platelets too.

Honestly, this concern rests on very thin evidence, mostly a single case report in someone who was also on warfarin and aspirin. So it's more of a theoretical caution than a proven problem. Still, watch for signs like easy bruising, dark or bloody stools, stomach pain, or any unusual bleeding. Before adding diosmin, it's worth a quick chat with your pharmacist or doctor.

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
Moderate

DICLOFENAC (Voltaren, others)

3 of 3
Theoretically, diosmin might increase the levels and clinical effects of diclofenac.
Clinical and laboratory research shows that diosmin inhibits the metabolism of diclofenac. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of diclofenac 100 mg increases blood levels of diclofenac and decreases diclofenac clearance. It is speculated that diosmin reduces the metabolism of diclofenac by inhibiting cytochrome P450 2C9 (CYP2C9).
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Arthrotec is a combo pill: diclofenac (an anti-inflammatory) plus misoprostol (added to protect your stomach). The interaction here is really about the diclofenac part. Your body clears diclofenac using a liver enzyme called CYP2C9, and diosmin appears to slow that enzyme down. In a human study, people who took diosmin for several days had higher diclofenac levels and cleared it more slowly. So this is an active drug being blocked from breakdown, not a prodrug, which means diclofenac can build up.

Practically, more diclofenac in your system can mean a higher chance of typical NSAID side effects like stomach upset, heartburn, ulcers or bleeding, fluid retention, or kidney strain. The evidence is decent but not huge, so don't panic. Just check with your pharmacist or doctor before pairing them, and watch for stomach pain or dark stools.

References
  1. Rajnarayana K, Venkatesham A, Krishna DR. Bioavailability of diclofenac sodium after pretreatment with diosmin in healthy volunteers. Drug Metabol Drug Interact. 2007;22(2-3):165-74. PubMed
  2. Poór M, Boda G, Mohos V, et al. Pharmacokinetic interaction of diosmetin and silibinin with other drugs: Inhibition of CYP2C9-mediated biotransformation and displacement from serum albumin. Biomed Pharmacother. 2018;102:912-921. 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 Diclofenac Sodium, Misoprostol 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 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 Diclofenac Sodium, Misoprostol

This page covers Diosmin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diclofenac Sodium, Misoprostol page lists 306 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Piracetam (major).

By severity: 7 major · 265 moderate · 34 minor.

From our pharmacist’s overview on the Diclofenac Sodium, Misoprostol page

“Alcohol is the plainest hazard on this list. Beer and wine both carry major ratings with Arthrotec (diclofenac sodium and misoprostol) because mixing an NSAID with alcohol raises the risk of stomach bleeding, and bleeding is the thread running through most of these 306 entries.”

Reviewed by 2 · Jul 18, 2026

Open the Diclofenac Sodium, Misoprostol 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 Diclofenac Sodium, Misoprostol 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 Diclofenac Sodium, Misoprostol 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

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

29 days ago today
Medication Diclofenac Sodium, Misoprostol
Steady interest

#2,400 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
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
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
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 Diosmin and Diclofenac Sodium, Misoprostol Together: Common Questions

Can you take Diosmin with Diclofenac Sodium, Misoprostol?
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 Diclofenac Sodium, Misoprostol?
Diclofenac Sodium, Misoprostol 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 Diclofenac Sodium, Misoprostol 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.