Drug & supplement interaction

Hesperidin + Codeine Phosphate

Codeine Phosphate brand name: Codeine.

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

Hesperidin has a moderate interaction with Codeine Phosphate. Theoretically, concomitant use with CNS depressants may cause additive sedative effects.

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

Hesperidin and Codeine Phosphate

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CNS DEPRESSANTS

Why this applies to Codeine Phosphate

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 simple version: codeine is already a sedating medicine. It can make you drowsy, slow your breathing a bit, and leave you feeling foggy or tired. Hesperidin, the citrus flavonoid, has shown mild sedative-type activity in animal studies, partly by acting on opioid receptors. The concern is that stacking the two could add up and make you sleepier than you'd expect.

But keep this in perspective. This interaction is theoretical and comes only from animal research, not from people. It has not been reported in humans, so I wouldn't lose sleep over it. The amount of hesperidin you'd get from eating an orange is unlikely to matter. If you take a concentrated hesperidin supplement alongside codeine, just mention it to your pharmacist or doctor and watch for extra drowsiness.

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

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 Codeine Phosphate one above is one of them. If you take anything else, check it against the full list below.

Moderate 701 No known interaction 2,129 (incl. 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.

From our Q&A

Questions About Hesperidin or Codeine Phosphate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Hesperidin or Codeine Phosphate, 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 Codeine Phosphate

This page covers Hesperidin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Codeine Phosphate page lists 144 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 114 moderate · 23 minor.

From our pharmacist’s overview on the Codeine Phosphate page

“Codeine phosphate is an opioid painkiller and cough suppressant that slows breathing along with brain activity, and the wrong supplement can push that effect into dangerous territory. Seven of the 144 documented ingredients rate major, and nearly all of that serious risk comes from things that deepen sedation.”

Reviewed by 2 · Jul 18, 2026

Open the 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 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 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%

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

29 days ago today
Medication Codeine Phosphate
Top 25%

#460 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
Medication

About Codeine

What Is Codeine Used For?

Brand name: Codeine

Codeine Sulfate tablets are used for the management of mild to moderate pain in adults and adolescents when other treatments have not worked well enough or are not tolerated. It is an opioid medication, so it is only appropriate when non-opioid options are inadequate.

Because of its serious risks — including addiction, misuse, and overdose — codeine is reserved for patients who truly need an opioid. Prescribers are expected to use the lowest effective dose for the shortest time possible.

See full Codeine drug information
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 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 Codeine Phosphate supplement interactions › Every supplement checked against Codeine Phosphate, ranked by severity Codeine 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 Hesperidin and Codeine Phosphate Together: Common Questions

Can you take Hesperidin with 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.
How serious is the Hesperidin and 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

Still Have a Question About Codeine Phosphate and Hesperidin?

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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.