Drug & supplement interaction

Peony + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

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

Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 drug categories that Peony can interact with; the most serious is rated moderate. Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peony and Diphenhydramine Hydrochloride, Naproxen Sodium

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Peony interacts with.

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. 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

Aleve PM combines naproxen (a pain reliever) with diphenhydramine, the same sleep aid found in Benadryl. The concern here is mostly with the diphenhydramine side. Peony has been shown, in test tube studies only, to mildly slow down the CYP1A2 enzyme, one of the pathways your body uses to clear certain drugs. If that slowdown happened in real life, this medicine could linger a bit longer and feel stronger, meaning more next-day grogginess, dry mouth, dizziness, or constipation.

Honestly, this is theoretical and has never been confirmed in people, so I wouldn't lose sleep over it. Still, since both ingredients already cause drowsiness, it's worth a quick chat with your pharmacist before pairing them, especially if you feel unusually foggy.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects.
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 connection with Aleve PM: the naproxen part is an NSAID, and on its own NSAIDs can thin the blood a little and irritate the stomach lining. Peony root has shown some blood-thinning and anti-clotting activity, but that's only in lab and test-tube studies, not in people. So this is a theoretical concern rather than something we've clearly seen happen.

The worry, if it adds up, would be a slightly higher chance of bruising, nosebleeds, or stomach upset and bleeding (dark stools, stomach pain). The diphenhydramine (the PM part) mainly makes you drowsy and isn't really part of this. To stay safe, just check with your pharmacist or doctor before pairing them, especially if you bruise easily or have stomach issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Koo YK, Kim JM, Koo JY, et al. Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa. Pharmazie 2010;65(8):624-8.

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

Peony Also Interacts With Other Medications

Peony has 812 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.

Moderate 812 No known interaction 2,018 (incl. Diphenhydramine Hydrochloride, Naproxen Sodium)
Taking anything else?

Check Another of Your Medications Against Peony

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium

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

We hold 71 real supplement products containing Peony, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Peony. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Peony — 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 Peony 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 Peony
Top 25%

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

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Top 5%

#79 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 Peony

What is Peony?

Peony
  • Menstrual cramps and irregular periods
  • Muscle cramps and spasms
  • Anxiety and stress
  • Inflammation and pain
  • Polycystic ovary syndrome (PCOS)

Peony root is a traditional Chinese medicine herb often used for menstrual problems, cramps, and inflammation, frequently as part of combination formulas. Human evidence for most uses is limited or preliminary, so it should not replace proven treatments. Talk to your pharmacist or doctor before using it, especially if you are pregnant, breastfeeding, or taking other medicines.

Read the full Peony monograph & all interactions
Keep checking

Other Drugs & Peony

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

0Major
812Moderate
0Minor
2,017No known interaction
812 Moderate 2,017 No interaction
Moderate

812 interactions

Showing 60 of 812 moderate interactions — see all 812 on the Peony page.

No interaction 2,017 drugs checked — show the list

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

Showing the 60 most looked-up of 2,017 medications checked with no known interaction — see the full Peony list.

See the full Peony 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
Peony 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 Peony and Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions

Can you take Peony with Diphenhydramine Hydrochloride, Naproxen Sodium?
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.
Why are there 2 interactions listed for Peony and Diphenhydramine Hydrochloride, Naproxen Sodium?
Diphenhydramine Hydrochloride, Naproxen Sodium belongs to more than one drug category, and Peony 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 Peony and Diphenhydramine Hydrochloride, Naproxen Sodium 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 Hydrochloride, Naproxen Sodium and Peony?

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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.