Drug & supplement interaction

Hesperidin + Aspirin, Codeine Phosphate

Aspirin, Codeine Phosphate brand name: Aspirin w/ Codeine.

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

Aspirin, Codeine Phosphate 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 Aspirin, Codeine Phosphate

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. Aspirin, Codeine Phosphate 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 Aspirin, Codeine Phosphate

Aspirin, Codeine Phosphate 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

Here's the short version: the codeine part of your aspirin-codeine combo is an opioid that already causes drowsiness, and hesperidin may add a little extra sedation. In animal studies, hesperidin showed mild calming effects by tickling the same opioid receptors codeine works on. So in theory, taking them together could leave you a bit sleepier, foggier, or more lightheaded than usual.

The honest truth is this is very weak evidence. It comes from lab and animal work, not from people, so I wouldn't lose sleep over it. Still, if you notice unusual drowsiness or feel unsteady, take it easy and check in with your pharmacist or doctor before combining them regularly.

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

Aspirin, Codeine Phosphate 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

Here's the situation with your aspirin and codeine combo. The aspirin part already thins your blood a bit by making platelets less sticky, which is how it helps your heart but also why it can cause bruising or bleeding. Hesperidin, the citrus flavonoid in your supplement, may have a mild blood-thinning action of its own. So in theory, taking them together could add up and slightly raise your risk of bleeding, like nosebleeds, easy bruising, or stomach upset.

That said, this concern comes only from lab and animal studies, not real human reports, so it's quite theoretical. The codeine side isn't involved here. Eating citrus fruit won't be an issue, but concentrated supplement doses are worth mentioning to your pharmacist or doctor, especially before any surgery.

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 Aspirin, Codeine Phosphate 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. Aspirin, Codeine Phosphate)
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 Aspirin, Codeine Phosphate

This page covers Hesperidin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Codeine Phosphate page lists 327 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: 11 major · 281 moderate · 35 minor.

From our pharmacist’s overview on the Aspirin, Codeine Phosphate page

“Aspirin with codeine pairs a blood-thinning pain reliever with an opioid, and the 327 ingredients on this page reflect both halves, so this combination deserves genuine care before any supplement joins it. Most of the list, over 200 ingredients, can add to aspirin's effect on platelets and raise bleeding risk.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Codeine Phosphate 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 Aspirin, Codeine Phosphate 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 Aspirin, Codeine Phosphate 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%

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

29 days ago today
Medication Aspirin, Codeine Phosphate
Top half

#900 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 Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate supplement interactions › Every supplement checked against Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate Together: Common Questions

Can you take Hesperidin with Aspirin, Codeine Phosphate?
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 Aspirin, Codeine Phosphate?
Aspirin, Codeine Phosphate 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 Aspirin, Codeine Phosphate 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.