Drug & supplement interaction

Hesperidin + Zolpidem

Zolpidem brand names: Ambien CR, Intermezzo, Sublinox.

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

Hesperidin has a moderate interaction with Zolpidem. 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 Zolpidem

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

Moderate

CNS DEPRESSANTS

Why this applies to Zolpidem

Zolpidem 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 these two together. Zolpidem already works by calming activity in your brain to help you drift off. Hesperidin, in animal studies, showed mild sedative effects of its own and seemed to deepen sleepiness when paired with a calming medication. The worry is simply that the two could add up, leaving you groggier than expected, more dizzy, or unsteady on your feet, especially if you get up during the night.

I want to be honest about the strength of this: it's theoretical and comes from lab and animal work, not real human reports. So it's not a reason to panic. Still, since zolpidem can cause next-morning drowsiness on its own, it's worth a quick word with your pharmacist or doctor before combining them.

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 Zolpidem 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. Zolpidem)
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 Zolpidem

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 Zolpidem, 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 Zolpidem

This page covers Hesperidin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Zolpidem page lists 195 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: 9 major · 147 moderate · 39 minor.

From our pharmacist’s overview on the Zolpidem page

“Zolpidem (Ambien, Intermezzo) is a sleep medicine that works by slowing the brain, and the 195 supplements and herbal ingredients on this page deserve genuine care, starting with the nine rated major. Most of the list pulls in one of two directions.”

Reviewed by 2 · Jul 18, 2026

Open the Zolpidem 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 Zolpidem 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 Zolpidem 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%

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

29 days ago today
Medication Zolpidem
Top 25%

#380 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 Zolpidem

What Is Zolpidem Used For?

Brand names: Ambien CR, Intermezzo, Sublinox

Zolpidem is used short-term for insomnia. Most formulations — including Ambien, oral tablets, and Zolpidem Tartrate Capsules — are approved to help people who have trouble falling asleep at bedtime. Zolpidem Tartrate Capsules are specifically indicated for adults under 65.

The extended-release formulations (including Zolpidem Tartrate Extended-Release Tablets) help with both falling asleep and staying asleep through the night. Sublingual tablets (Edluar, Zolpidem Tartrate Sublingual Tablet, and Zolpidem tartrate sublingual) are taken as needed when you wake up in the middle of the night and cannot get back to sleep — but only if at least 4 hours of sleep time remain before you need to be up.

See full Zolpidem 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 Zolpidem, 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 Zolpidem supplement interactions › Every supplement checked against Zolpidem, ranked by severity Zolpidem 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 Zolpidem Together: Common Questions

Can you take Hesperidin with Zolpidem?
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 Zolpidem 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 Zolpidem 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.