Drug & supplement interaction

Peppermint + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

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

Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 drug categories that Peppermint can interact with; the most serious is rated moderate. Theoretically, peppermint might increase the levels of CYP2C9 substrates.

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

Peppermint and Diphenhydramine Hydrochloride, Naproxen Sodium

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

Why Are There 2 Interactions?

Peppermint interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 of those categories, so it can interact with Peppermint 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 2C9 (CYP2C9) SUBSTRATES

1 of 2

Why this applies to Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Peppermint interacts with.

Theoretically, peppermint might increase the levels of CYP2C9 substrates.
In vitro research shows that peppermint oil inhibits CYP2C9. So far, this interaction 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 (an anti-inflammatory pain reliever) with diphenhydramine (a sedating antihistamine for sleep). The naproxen part is partly cleared by a liver enzyme called CYP2C9. In a test tube, peppermint oil slowed that enzyme down, which in theory could let naproxen build up a bit higher than usual.

Here's the honest part: this has only been seen in lab studies, never in real people, so I wouldn't lose sleep over it. If anything, watch for the usual naproxen complaints like stomach upset, heartburn, or irritation, which is worth noting since peppermint can also cause heartburn. Occasional use is unlikely to be a problem, but if you take Aleve PM regularly, run it by your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, peppermint might increase the levels of CYP1A2 substrates.
In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2. However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference.
Severity Minor Likelihood Possible Evidence B

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 and inflammation reliever) with diphenhydramine (the same sleepy antihistamine found in Benadryl). The concern here is mostly theoretical. In lab and animal studies, peppermint oil seems to slow down a liver enzyme called CYP1A2. If that happened in your body, these medicines could clear a little slower and build up slightly, which in plain terms might mean more next-day grogginess, dry mouth, or stomach upset.

The good news: in actual human research, peppermint tea did not meaningfully change how a CYP1A2 drug was handled. So for most people, an occasional cup of peppermint tea or normal food amounts are unlikely to cause trouble. Concentrated peppermint oil capsules are more of a question mark. If you take Aleve PM often, just check with your pharmacist or doctor to be safe.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  3. Begas E, Tsioutsiouliti A, Kouvaras E, et al. Effects of peppermint tea consumption on the activities of CYP1A2, CYP2A6, Xanthine Oxidase, N-acetyltranferase-2 and UDP-glucuronosyltransferases-1A1/1A6 in healthy volunteers. Food Chem Toxicol 2017;100:80-9 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

Peppermint Also Interacts With Other Medications

Peppermint has 730 moderate, 65 minor 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 730 Minor 65 No known interaction 2,035 (incl. Diphenhydramine Hydrochloride, Naproxen Sodium)
Taking anything else?

Check Another of Your Medications Against Peppermint

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium

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

We hold 1,980 real supplement products containing Peppermint, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Peppermint. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Peppermint — 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 Peppermint 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 Peppermint
Top 10%

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

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Steady interest

#1,902 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 Peppermint

What is Peppermint?

Peppermint
  • Irritable bowel syndrome (IBS)
  • Indigestion and gas
  • Nausea
  • Tension headache (topical oil)
  • Colds and congestion
  • Freshening breath

Peppermint is a popular herb with the best evidence supporting enteric-coated peppermint oil for easing IBS symptoms. It is generally well tolerated for most adults, but it can cause heartburn and is not recommended in concentrated oil form for infants and young children. Check with your pharmacist or doctor before using it regularly, especially during pregnancy or breastfeeding.

Read the full Peppermint monograph & all interactions
Keep checking

Other Drugs & Peppermint

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

0Major
730Moderate
65Minor
2,034No known interaction
730 Moderate 65 Minor 2,034 No interaction
Moderate

730 interactions

Showing 60 of 730 moderate interactions — see all 730 on the Peppermint page.

Minor

65 interactions

Showing 60 of 65 minor interactions — see all 65 on the Peppermint page.

No interaction 2,034 drugs checked — show the list

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

Showing the 60 most looked-up of 2,034 medications checked with no known interaction — see the full Peppermint list.

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

Can you take Peppermint 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 Peppermint and Diphenhydramine Hydrochloride, Naproxen Sodium?
Diphenhydramine Hydrochloride, Naproxen Sodium belongs to more than one drug category, and Peppermint 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 Peppermint 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 Peppermint?

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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.