Drug & supplement interaction

Hesperidin + acetaminophen, dextromethorphan, doxylamine

acetaminophen, dextromethorphan, doxylamine brand name: NyQuil.

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

Hesperidin has a moderate interaction with acetaminophen, dextromethorphan, doxylamine. 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 acetaminophen, dextromethorphan, doxylamine

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

Moderate

CNS DEPRESSANTS

Why this applies to acetaminophen, dextromethorphan, doxylamine

acetaminophen, dextromethorphan, doxylamine 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 gist with NyQuil and hesperidin. NyQuil already has built-in sleepiness from the doxylamine (an antihistamine) and to some degree the dextromethorphan. In animal studies, hesperidin showed mild sedative effects through opioid receptor activity, so the theory is that stacking it with a sedating product like NyQuil could add up to a bit more drowsiness, grogginess, or that heavy-headed feeling the next morning.

I want to be honest about the evidence here. This has only been seen in lab and animal research, never reported in people, so it's more of a caution than a real-world warning. Still, if you notice extra drowsiness, take it easy and skip driving. Just give your pharmacist a quick heads-up if you take hesperidin 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

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 acetaminophen, dextromethorphan, doxylamine 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. acetaminophen, dextromethorphan, doxylamine)
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 acetaminophen, dextromethorphan, doxylamine

This page covers Hesperidin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the acetaminophen, dextromethorphan, doxylamine page lists 106 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 Grapefruit (major).

By severity: 8 major · 78 moderate · 20 minor.

From our pharmacist’s overview on the acetaminophen, dextromethorphan, doxylamine page

“NyQuil (acetaminophen, dextromethorphan, doxylamine) is designed to make you drowsy, and that is exactly where most of its supplement interactions live. Seventy-eight of the 106 ingredients on this list add to its sedation, and the eight rated major, alcohol and kava among them, can push a nighttime cold remedy toward serious depressio…”

Reviewed by 2 · Jul 18, 2026

Open the acetaminophen, dextromethorphan, doxylamine 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 acetaminophen, dextromethorphan, doxylamine 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 acetaminophen, dextromethorphan, doxylamine 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%

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

29 days ago today
Medication acetaminophen, dextromethorphan, doxylamine
Top 5%

#65 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 acetaminophen, dextromethorphan, doxylamine, 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 acetaminophen, dextromethorphan, doxylamine supplement interactions › Every supplement checked against acetaminophen, dextromethorphan, doxylamine, 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 acetaminophen, dextromethorphan, doxylamine Together: Common Questions

Can you take Hesperidin with acetaminophen, dextromethorphan, doxylamine?
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 acetaminophen, dextromethorphan, doxylamine 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 acetaminophen, dextromethorphan, doxylamine 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.