Drug & supplement interaction

Wine + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

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

Wine has a major interaction with Diphenhydramine, Pseudoephedrine. Concomitant use may increase sedative and other adverse effects.

Read the full interaction report
SeverityMajor
LikelihoodLikely
EvidenceC
What do Severity, Likelihood & Evidence mean?
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Interaction report

Wine and Diphenhydramine, Pseudoephedrine

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

Major

CNS DEPRESSANTS

Why this applies to Diphenhydramine, Pseudoephedrine

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

Concomitant use may increase sedative and other adverse effects.
Concomitant use of alcohol with CNS depressants can increase sedative and other adverse effects, potentially through inhibition of the metabolism of certain CNS depressants.
Severity Major Likelihood Likely Evidence C

Well-controlled human studies have demonstrated the likely existence of this interaction.

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

Here's the thing to watch with Actifed Allergy: it contains diphenhydramine, the same sedating antihistamine found in Benadryl. On its own, it already makes a lot of people drowsy, foggy, and slow to react. When you add wine, the alcohol piles on top of that. Both calm down the brain, so together they can leave you much sleepier, dizzier, and more impaired than you'd expect, sometimes dangerously so behind the wheel.

The pseudoephedrine part is a stimulant, but it doesn't cancel out the drowsiness, and mixing it with alcohol can also bother some people's stomach or heart. This is a well-recognized combination to avoid. If you want a glass of wine, talk with your pharmacist about timing or a non-sedating option.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Fraser AG. Pharmacokinetic interactions between alcohol and other drugs. Clin Pharmacokinet 1997;33:79-90. 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

Wine Also Interacts With Other Medications

Wine has 655 major, 270 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.

Major 655 Moderate 270 No known interaction 1,905 (incl. Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Wine

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine, Pseudoephedrine

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

We hold 8 real supplement products containing Wine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Wine. Your product may carry other ingredients that interact with Diphenhydramine, Pseudoephedrine too, on top of Wine — 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 Wine 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 Wine
Top half

#553 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 Wine

What is Wine?

  • Social and relaxation use
  • Heart health (popular belief)
  • Antioxidant intake
  • Aiding digestion (traditional use)
  • Culinary flavoring

Wine is an alcoholic beverage made from fermented grapes and is not a true dietary supplement or medicine. Despite popular claims about heart benefits, the alcohol it contains carries real health risks, and no amount of drinking can be recommended to improve health. If you drink, do so in moderation, and avoid alcohol entirely during pregnancy or if you have certain medical conditions.

Read the full Wine monograph & all interactions
Keep checking

Other Drugs & Wine

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

655Major
270Moderate
0Minor
1,904No known interaction
655 Major 270 Moderate 1,904 No interaction
Major

655 interactions

Showing 60 of 655 major interactions — see all 655 on the Wine page.

Moderate

270 interactions

Showing 60 of 270 moderate interactions — see all 270 on the Wine page.

No interaction 1,904 drugs checked — show the list

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

Showing the 60 most looked-up of 1,904 medications checked with no known interaction — see the full Wine list.

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

Can you take Wine with Diphenhydramine, Pseudoephedrine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Wine and Diphenhydramine, Pseudoephedrine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Diphenhydramine, Pseudoephedrine and Wine?

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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.