Drug & supplement interaction

Adrue + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

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

Adrue has a moderate interaction with Diphenhydramine, Pseudoephedrine. Animal research suggests that taking adrue in combination with sodium thiopental or diazepam increases total sleep time up to four-fold compared to the effects of the drugs alone.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Adrue and Diphenhydramine, Pseudoephedrine

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

Moderate

CNS DEPRESSANTS

Why this applies to Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine falls under CNS DEPRESSANTS — the group Adrue interacts with.

Animal research suggests that taking adrue in combination with sodium thiopental or diazepam increases total sleep time up to four-fold compared to the effects of the drugs alone. Theoretically, concomitant use of adrue with CNS depressants might cause additive sedation. Some CNS depressants include benzodiazepines, such as diazepam (Valium), alprazolam (Xanax), triazolam (Halcion), and estazolam (ProSom); barbiturates, such as mephobarbital (Mebaral), phenobarbital (Luminal Sodium), and pentobarbital sodium (Nembutal); zolpidem (Ambien); and others.
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 thing to keep an eye on with Actifed Allergy: the diphenhydramine half is an antihistamine that already makes a lot of people drowsy and foggy. Adrue has a traditional reputation as a mild calming agent, and in animal studies it seemed to lengthen sleep time when paired with sedative drugs. Putting the two together could, in theory, stack that sedation, so you might feel sleepier, slower, or more dizzy than usual.

Now, be fair to the evidence here. This is based only on lab and animal work, not human trials, so it's more of a caution than a proven problem. The pseudoephedrine part is actually a stimulant and may offset some drowsiness. Still, if you plan to drive or have a few alcoholic drinks, run it by your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rakotonirina, V. S., Bum, E. N., Rakotonirina, A., and Bopelet, M. Sedative properties of the decoction of the rhizome of Cyperus articulatus. Fitoterapia 2001;72(1):22-29. 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

Adrue Also Interacts With Other Medications

Adrue has 255 moderate known drug interactions in our database — the Diphenhydramine, Pseudoephedrine one above is one of them. If you take anything else, check it against the full list below.

Moderate 255 No known interaction 2,575 (incl. Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Adrue

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine, Pseudoephedrine

This page covers Adrue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine, Pseudoephedrine page lists 185 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), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 150 moderate · 22 minor.

From our pharmacist’s overview on the Diphenhydramine, Pseudoephedrine page

“This medicine pulls in two directions at once, which is exactly why the supplement list for diphenhydramine and pseudoephedrine (Actifed Allergy) is not one to skim. The antihistamine half is sedating, so anything else that slows the brain deepens drowsiness; beer, wine, and kava all carry major ratings, with alcohol the best documented.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine, Pseudoephedrine interaction page

One more smart check

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

We hold 6 real supplement products containing Adrue, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Adrue. Your product may carry other ingredients that interact with Diphenhydramine, Pseudoephedrine too, on top of Adrue — 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 Adrue and Diphenhydramine, Pseudoephedrine 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 Adrue
Top half

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

29 days ago today
Medication Diphenhydramine, Pseudoephedrine
Steady interest

#1,484 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 Adrue

What is Adrue?

Adrue
  • Nausea and vomiting
  • Digestive upset, gas, and diarrhea
  • Calming or sedative effect
  • Traditional use for fevers and infections

Adrue (Cyperus articulatus) is a sedge whose rhizome has long been used in traditional medicine for nausea and other stomach complaints, and as a mild calming agent. Solid human studies are lacking, so its real benefits and safe doses are not well established. Talk to a pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Adrue monograph & all interactions
Keep checking

Other Drugs & Adrue

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

0Major
255Moderate
0Minor
2,574No known interaction
255 Moderate 2,574 No interaction
Moderate

255 interactions

Showing 60 of 255 moderate interactions — see all 255 on the Adrue page.

No interaction 2,574 drugs checked — show the list

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

Showing the 60 most looked-up of 2,574 medications checked with no known interaction — see the full Adrue list.

See the full Adrue interactions page
See every supplement checked against Diphenhydramine, Pseudoephedrine, 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
Adrue monograph › Uses, safety, and every drug interaction in one place Diphenhydramine, Pseudoephedrine supplement interactions › Every supplement checked against Diphenhydramine, Pseudoephedrine, 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 Adrue and Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take Adrue with Diphenhydramine, Pseudoephedrine?
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 Adrue and Diphenhydramine, Pseudoephedrine 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 Diphenhydramine, Pseudoephedrine and Adrue?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.