Drug & supplement interaction

Hesperidin + Ibuprofen, Oxycodone

Ibuprofen, Oxycodone brand name: Combunox.

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

Ibuprofen, Oxycodone falls into 2 drug categories that Hesperidin can interact with; the most serious is rated moderate. Theoretically, concomitant use with CNS depressants may cause additive sedative effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Hesperidin and Ibuprofen, Oxycodone

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Hesperidin interacts with whole categories of medication. Ibuprofen, Oxycodone falls into 2 of those categories, so it can interact with Hesperidin in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Ibuprofen, Oxycodone

Ibuprofen, Oxycodone falls under CNS DEPRESSANTS — the group Hesperidin interacts with.

Theoretically, concomitant use with CNS depressants may cause additive sedative effects.
Animal studies show that hesperidin has sedative effects, due to opioid receptor activity and can increase sedation when used with diazepam. This effect 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

Combunox pairs ibuprofen with oxycodone, and it's the oxycodone half that matters here. Oxycodone is an opioid that can make you drowsy and slow your breathing. In animal studies, hesperidin seemed to have its own mild sedative effect by acting on opioid receptors. The thinking is that stacking it on top of an opioid could add to that sleepy, foggy feeling.

I'll be honest with you: this is only a theoretical concern based on lab and animal data, and it hasn't been seen in people. So I wouldn't lose sleep over it. Still, if you notice extra grogginess, dizziness, or feel unusually out of it, mention it to your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Fernandez, S. P., Wasowski, C., Paladini, A. C., and Marder, M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur.J.Pharmacol. 4-11-2005;512(2-3):189-198. PubMed
  2. Loscalzo, L. M., Wasowski, C., Paladini, A. C., and Marder, M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur.J.Pharmacol. 2-12-2008;580(3):306-313. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

Ibuprofen, Oxycodone also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity.
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

The product you're asking about (Combunox) pairs ibuprofen with oxycodone. The piece that matters here is the ibuprofen. As an anti-inflammatory (NSAID), ibuprofen already makes platelets a little less sticky and can irritate the stomach lining, so it carries a built-in bleeding and stomach-bleed risk on its own.

Hesperidin, a citrus flavonoid, has shown mild antiplatelet activity, but only in lab and animal studies, so this is a theoretical concern rather than something well documented in people. Stacked together, they could in theory nudge your bleeding risk up a bit. Watch for easy bruising, nosebleeds, dark or bloody stools, or stomach pain. Normal citrus in your diet is unlikely to matter; concentrated supplements are the question. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Jin, Y. R., Han, X. H., Zhang, Y. H., Lee, J. J., Lim, Y., Chung, J. H., and Yun, Y. P. Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity. Atherosclerosis 200

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

Hesperidin Also Interacts With Other Medications

Hesperidin has 701 moderate known drug interactions in our database — the Ibuprofen, Oxycodone one above is among them. If you take anything else, check it against the full list below.

Moderate 701 No known interaction 2,129 (incl. Ibuprofen, Oxycodone)
Taking anything else?

Check Another of Your Medications Against Hesperidin

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

Everything else you take

See Every Supplement That Interacts With Ibuprofen, Oxycodone

This page covers Hesperidin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ibuprofen, Oxycodone page lists 356 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 13 major · 303 moderate · 40 minor.

From our pharmacist’s overview on the Ibuprofen, Oxycodone page

“Combunox puts oxycodone, an opioid, together with the NSAID ibuprofen, and I want you to read this page carefully rather than skim it. Of the 356 supplements and herbs on file, 202 can raise your bleeding risk on top of what ibuprofen already does, and 78 can deepen the drowsiness and slowed breathing that come with oxycodone.”

Reviewed by 2 · Jul 18, 2026

Open the Ibuprofen, Oxycodone interaction page

One more smart check

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

We hold 1,895 real supplement products containing Hesperidin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Hesperidin. Your product may carry other ingredients that interact with Ibuprofen, Oxycodone too, on top of Hesperidin — 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 Hesperidin and Ibuprofen, Oxycodone 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 Hesperidin
Top 25%

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

29 days ago today
Medication Ibuprofen, Oxycodone
Steady interest

#1,741 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 Hesperidin

What is Hesperidin?

Hesperidin
  • Hemorrhoids
  • Varicose veins and poor circulation
  • Leg swelling (venous insufficiency)
  • High blood pressure
  • Antioxidant support

Hesperidin is a flavonoid found in citrus fruits that is often combined with diosmin and used for vein and circulation problems like hemorrhoids and varicose veins. Some evidence supports these uses, but data for many other claims is limited. It is generally well tolerated, but pregnant and breastfeeding people should avoid it because safety has not been established.

Read the full Hesperidin monograph & all interactions
Keep checking

Other Drugs & Hesperidin

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

0Major
701Moderate
0Minor
2,128No known interaction
701 Moderate 2,128 No interaction
Moderate

701 interactions

Showing 60 of 701 moderate interactions — see all 701 on the Hesperidin page.

No interaction 2,128 drugs checked — show the list

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

Showing the 60 most looked-up of 2,128 medications checked with no known interaction — see the full Hesperidin list.

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

Can you take Hesperidin with Ibuprofen, Oxycodone?
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 Hesperidin and Ibuprofen, Oxycodone?
Ibuprofen, Oxycodone belongs to more than one drug category, and Hesperidin 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 Hesperidin and Ibuprofen, Oxycodone 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.