Drug & supplement interaction

Wine + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

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

Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 drug categories that Wine can interact with; the most serious is rated major. Concomitant use may increase sedative and other adverse effects.

Read the full interaction report
SeverityMajor
LikelihoodLikely
Interactions2
EvidenceC
What do Severity, Likelihood & Evidence mean?
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Interaction report

Wine and Diphenhydramine Hydrochloride, Naproxen Sodium

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Wine interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 of those categories, so it can interact with Wine in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 2

Why this applies to Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium 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

Aleve PM pairs naproxen (a pain reliever) with diphenhydramine, the same drowsy antihistamine found in Benadryl. That sleep-inducing ingredient is the issue here. Adding wine on top of it stacks two things that slow down your brain, so the sedation can hit harder than you'd expect. Think heavier drowsiness, dizziness, foggy thinking, poor coordination, and a real risk of being more impaired than you realize behind the wheel or on the stairs.

There's a second concern that's easy to miss: naproxen is an NSAID, and alcohol can irritate the stomach lining and raise the chance of stomach upset or bleeding. The safest move is to skip the wine on nights you take Aleve PM. If you have questions about your own situation, your pharmacist or doctor can help.

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
Major

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

2 of 2

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs).

Concomitant use may increase the risk of gastrointestinal (GI) bleeding.
Concomitant use of NSAIDs with alcohol may increase the risk of GI bleeding.
Severity Major Likelihood Probable Evidence C

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

Aleve PM combines naproxen, an anti-inflammatory pain reliever, with diphenhydramine, a sedating antihistamine. The part that matters most when alcohol is in the picture is the naproxen. NSAIDs like naproxen can irritate the stomach lining, and wine adds to that irritation, raising the odds of stomach bleeding. Warning signs include stomach pain, black or tarry stools, or vomit that looks like coffee grounds.

On top of that, the diphenhydramine in Aleve PM makes you drowsy, and wine deepens that effect, so you may feel extra sleepy, dizzy, or unsteady. This is a well-recognized concern, not just a theory. Please check with your pharmacist or doctor before mixing the two.

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 Hydrochloride, Naproxen Sodium one above is among them. If you take anything else, check it against the full list below.

Major 655 Moderate 270 No known interaction 1,905 (incl. Diphenhydramine Hydrochloride, Naproxen Sodium)
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 Hydrochloride, Naproxen Sodium

This page covers Wine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine Hydrochloride, Naproxen Sodium page lists 378 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), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 13 major · 320 moderate · 45 minor.

From our pharmacist’s overview on the Diphenhydramine Hydrochloride, Naproxen Sodium page

“Aleve PM combines naproxen, an NSAID, with the sedating antihistamine diphenhydramine, and its supplement list earns genuine care rather than a quick skim. Thirteen of the 378 ingredients on file rate major, and the two largest themes track the pill's two halves.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine Hydrochloride, Naproxen Sodium 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 Hydrochloride, Naproxen Sodium 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 Hydrochloride, Naproxen Sodium 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

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

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Top 10%

#189 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 Hydrochloride, Naproxen Sodium, 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 Hydrochloride, Naproxen Sodium supplement interactions › Every supplement checked against Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Hydrochloride, Naproxen Sodium Together: Common Questions

Can you take Wine with Diphenhydramine Hydrochloride, Naproxen Sodium?
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.
Why are there 2 interactions listed for Wine and Diphenhydramine Hydrochloride, Naproxen Sodium?
Diphenhydramine Hydrochloride, Naproxen Sodium belongs to more than one drug category, and Wine interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Wine and Diphenhydramine Hydrochloride, Naproxen Sodium 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 Hydrochloride, Naproxen Sodium 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.