Drug & supplement interaction

Evening Primrose + 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 Evening Primrose can interact with; the most serious is rated moderate. Theoretically, evening primrose oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

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

Evening Primrose and Diphenhydramine Hydrochloride, Naproxen Sodium

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

Why Are There 2 Interactions?

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

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 2

Why this applies to Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Evening Primrose interacts with.

Theoretically, evening primrose oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Evening primrose oil contains gamma linolenic acid (GLA). There is preliminary clinical evidence that GLA can reduce platelet aggregation and prolong bleeding time.
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 something worth knowing about Aleve PM. The pain reliever part, naproxen, is an NSAID, and like other NSAIDs it can make your blood a little slower to clot and can be hard on your stomach lining. Evening primrose oil contains GLA, which (at least in early studies) may also make platelets a bit less sticky and lengthen bleeding time. Put the two together and you could, in theory, nudge up your bleeding risk a little more.

To be honest, this is a theoretical concern based mostly on how things work, not strong proof. Still, watch for easy bruising, nosebleeds, dark stools, or stomach upset. If you take this combo often, or use other blood thinners, check in with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Guivernau M, Meza N, Barja P, Roman O. Clinical and experimental study on the long-term effect of dietary gamma-linolenic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production. Prostaglandins Leukot Essent Fatty A PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, evening primrose may increase the levels and clinical effects of CYP2C9 substrates.
In vitro research shows that linoleic acid, a constituent of evening primrose oil, inhibits CYP2C9.
Severity Minor 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 situation with Aleve PM, which combines naproxen (a pain and inflammation reliever) and diphenhydramine (a sedating antihistamine that helps you sleep). The naproxen part is cleared by a liver enzyme called CYP2C9. Lab studies suggest a fatty acid in evening primrose oil might gently slow that enzyme down. In theory, that could let naproxen build up a little more than usual.

What that might look like: slightly stronger naproxen effects, like stomach upset, heartburn, or a bit more bleeding risk. Honestly, this is only a theoretical concern from test-tube data, and it's rated minor, so most people won't notice anything. Still, if you take evening primrose regularly or have a bleeding problem, run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zou L, Harkey MR, and Henderson GL. Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 8-16-2002;71(13):1579-1589. 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

Evening Primrose Also Interacts With Other Medications

Evening Primrose has 147 moderate, 86 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 147 Minor 86 No known interaction 2,597 (incl. Diphenhydramine Hydrochloride, Naproxen Sodium)
Taking anything else?

Check Another of Your Medications Against Evening Primrose

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium

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

We hold 98 real supplement products containing Evening Primrose, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Evening Primrose. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Evening Primrose — 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 Evening Primrose 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 Evening Primrose
Top half

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

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

#72 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 Evening Primrose

What is Evening Primrose?

Evening Primrose
  • Eczema and skin health
  • PMS symptoms
  • Breast pain (mastalgia)
  • Menopause symptoms
  • Inflammation
  • Diabetic nerve pain

Evening primrose oil is a seed oil rich in gamma-linolenic acid (GLA), an omega-6 fatty acid, that is popularly used for skin conditions, PMS, and breast pain. The evidence behind most of these uses is mixed or weak, and it is not proven to be a reliable treatment for any condition. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before starting it, especially if you are pregnant or have a bleeding disorder.

Read the full Evening Primrose monograph & all interactions
Keep checking

Other Drugs & Evening Primrose

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

0Major
147Moderate
86Minor
2,596No known interaction
147 Moderate 86 Minor 2,596 No interaction
Moderate

147 interactions

Showing 60 of 147 moderate interactions — see all 147 on the Evening Primrose page.

Minor

86 interactions

Showing 60 of 86 minor interactions — see all 86 on the Evening Primrose page.

No interaction 2,596 drugs checked — show the list

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

Showing the 60 most looked-up of 2,596 medications checked with no known interaction — see the full Evening Primrose list.

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

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

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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.