Drug & supplement interaction

Belladonna + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

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

Belladonna has a moderate interaction with Diphenhydramine, Pseudoephedrine. Belladonna may increase the risk of adverse effects when used concomitantly with anticholinergic drugs.

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

Belladonna and Diphenhydramine, Pseudoephedrine

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

Moderate

ANTICHOLINERGIC DRUGS

Why this applies to Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine falls under ANTICHOLINERGIC DRUGS — the group Belladonna interacts with.

Belladonna may increase the risk of adverse effects when used concomitantly with anticholinergic drugs.
Belladonna has anticholinergic activity and increases the activity of anticholinergic drugs.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know with Actifed Allergy: the diphenhydramine part is already a strong anticholinergic, meaning it blocks that same acetylcholine messenger that belladonna's alkaloids block. Stack them together and you're essentially doubling down on the same effect. You'd be more likely to run into dry mouth, blurry vision, constipation, trouble urinating, a racing heartbeat, confusion, and feeling overheated since you sweat less. In older adults especially, that combo can tip into real confusion or dizziness.

This warning is based on how these drugs work rather than hard study data, so think of it as a sensible caution, not a proven disaster. Still, I wouldn't pair concentrated belladonna with this medicine without checking with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.

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

Belladonna Also Interacts With Other Medications

Belladonna has 195 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 195 No known interaction 2,635 (incl. Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Belladonna

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine, Pseudoephedrine

This page covers Belladonna 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 Belladonna as Part of a Dietary Supplement Product? Check It for Interactions

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

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

29 days ago today
Medication Diphenhydramine, Pseudoephedrine
Steady interest

#1,798 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 Belladonna

What is Belladonna?

  • Digestive cramps and spasms
  • Cold and flu symptoms (homeopathic)
  • Teething pain (homeopathic)
  • Motion sickness and nausea
  • Excess sweating or secretions
  • Pain and muscle spasm (topical plasters)

Belladonna is a highly toxic plant whose alkaloids (like atropine and scopolamine) are powerful medicines used only in carefully controlled, regulated forms. The raw plant and unregulated products can cause serious poisoning, and homeopathic versions have little proof of benefit. Never self-treat with belladonna without guidance from a doctor or pharmacist.

Read the full Belladonna monograph & all interactions
Keep checking

Other Drugs & Belladonna

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

0Major
195Moderate
0Minor
2,634No known interaction
195 Moderate 2,634 No interaction
Moderate

195 interactions

Showing 60 of 195 moderate interactions — see all 195 on the Belladonna page.

No interaction 2,634 drugs checked — show the list

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

Showing the 60 most looked-up of 2,634 medications checked with no known interaction — see the full Belladonna list.

See the full Belladonna 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
Belladonna 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 Belladonna and Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take Belladonna 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 Belladonna 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 Belladonna?

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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.