Oregon Grape + Diphenhydramine Hydrochloride, Naproxen Sodium
Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.
Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 drug categories that Oregon Grape can interact with; the most serious is rated moderate. Theoretically, Oregon grape might increase the sedative effects of CNS depressants.
Read the full interaction reportOregon Grape and Diphenhydramine Hydrochloride, Naproxen Sodium
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Oregon Grape interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 of those categories, so it can interact with Oregon Grape in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 3Why this applies to Diphenhydramine Hydrochloride, Naproxen Sodium
Diphenhydramine Hydrochloride, Naproxen Sodium falls under CNS DEPRESSANTS — the group Oregon Grape interacts with.
Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects.
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.
Here's the thing to keep in mind with Aleve PM: the diphenhydramine half is already a sedating antihistamine (that's the "PM" part, meant to help you sleep). Oregon grape contains berberine, and in animal studies only, berberine showed some calming, sedative-like effects. So the worry is that stacking it on top of diphenhydramine could add to that drowsiness.
If that played out, you might feel extra groggy, foggy, dizzy, or have a harder time waking up. I'll be honest though, this is a theoretical concern based on lab and animal data, not strong human studies, so it may be very mild or not noticeable at all. Still, please don't drive or mix it with alcohol, and check with your pharmacist or doctor before combining them.
- Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
- Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
- Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
- Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES
2 of 3Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.
Preliminary clinical evidence suggests that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2C9 (CYP2C9).
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.
Aleve PM is a combo of naproxen (a pain and inflammation reliever) and diphenhydramine (a sedating antihistamine to help you sleep). The naproxen half is partly broken down by a liver enzyme called CYP2C9. Berberine, the active compound in Oregon grape, may slow that enzyme down a bit. In theory, that could let naproxen build up a little higher than usual.
If that happens, you might notice more of naproxen's typical effects: stomach upset, heartburn, a higher risk of stomach irritation or bleeding, or fluid retention. Keep in mind this is based on limited, preliminary evidence, so it may not amount to much for most people. Still, since this is an over-the-counter product, it's worth a quick chat with your pharmacist before pairing them, especially if you take it often.
- Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
ANTICOAGULANT/ANTIPLATELET DRUGS
3 of 3Diphenhydramine Hydrochloride, Naproxen Sodium also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.
In vitro and in vivo research suggests that berberine, a constituent of Oregon grape, can inhibit platelet aggregation.
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.
Here's the practical picture with Aleve PM (which combines naproxen, an NSAID pain reliever, with diphenhydramine, an antihistamine that makes you sleepy). The naproxen half already nudges your blood toward bleeding a little by affecting how platelets stick together. Oregon grape contains berberine, and in lab and animal studies berberine also seems to slow platelet clumping. Stack those two together and, in theory, you could bruise more easily or have a touch more bleeding, such as from the stomach.
I want to be honest: this is a theoretical concern based only on test-tube and animal work, not strong human data, so don't panic. Still, if you take Aleve PM often or notice unusual bruising, dark stools, or stomach upset, check in with your pharmacist or doctor first.
- Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
- Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Oregon Grape Also Interacts With Other Medications
Oregon Grape has 1,217 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.
Check Another of Your Medications Against Oregon Grape
We haven’t checked that one against Oregon Grape yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Oregon Grape. Pick one to open its full report.
See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium
This page covers Oregon Grape 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
Taking Oregon Grape as Part of a Dietary Supplement Product? Check It for Interactions
We hold 740 real supplement products containing Oregon Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Oregon Grape. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Oregon Grape — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Oregon Grape 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.
#245 of 1,452 supplements looked up here in the last 7 days
#192 of 2,830 medications looked up here in the last 7 days
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.
About Oregon Grape
What is Oregon Grape?
- Psoriasis (topical)
- Eczema and other skin conditions
- Digestive upset
- Mild skin infections
- General 'detox' or tonic use
Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that may slightly ease psoriasis; evidence for other uses is limited. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.
Other Drugs & Oregon Grape
Browse every other medication we’ve checked against Oregon Grape — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,217 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Diphenhydramine ›
- Aspirin ›
- Hydrocortisone ›
- Insulin (rdna) ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Insulin (pork) ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Insulin (human) ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Amphetamine ›
- Buprenorphine ›
Showing 60 of 1,217 moderate interactions — see all 1,217 on the Oregon Grape page.
No interaction 1,612 drugs checked — show the list
We also checked Oregon Grape against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Acetaminophen ›
- Rosuvastatin ›
- Escitalopram ›
- Isotretinoin ›
- Docusate ›
- Valacyclovir ›
- Sumatriptan ›
- Hydroxyurea ›
- Levothyroxine, Liothyronine ›
- Methotrexate ›
- Amoxicillin ›
- Bupropion ›
- Azithromycin ›
- Bendamustine ›
- Acyclovir ›
- Methylene Blue ›
- Ciprofloxacin ›
- Amoxicillin, Clavulanate Potassium ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Ezetimibe ›
- Acetaminophen, Brompheniramine, Phenylpropanolamine ›
- Cephalexin ›
- Cyclopentolate ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Levodopa ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Alginic Acid, Aluminum Hydroxide ›
- Mitomycin ›
- Roxithromycin ›
- Daunorubicin, Cytarabine ›
- Efgartigimod Alfa-fcab ›
- Charcoal (otc Drug) ›
- Levothyroxine Sodium ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Magnesium Hydroxide (otc Drug) ›
- Atropine Methyl Nitrate, Digestive Enzymes ›
- Aminolevulinic Acid Hydrochloride ›
- Peginterferon Alfa-2a, Ribavirin ›
- Articaine, Epinephrine ›
- Alpha-1 Proteinase Inhibitor ›
- Acetaminophen, Butalbital ›
- Cytomegalovirus Immune Globulin ›
- Sodium Bicarbonate (otc Drug) ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Tubocurarine ›
- Flutemetamol F-18 ›
- Dexmethylphenidate ›
- Imipenem, Cilastatin, Relebactam ›
- Cefaclor ›
- Pyrilamine Maleate ›
- Hydroxychloroquine ›
- Ephedrine, Hydroxyzine, Theophylline ›
- Bleomycin ›
- Dihydroxyaluminum Sodium Carbonate ›
- Carbinoxamine Maleate ›
- Acetaminophen, Phenylpropanolamine, Phenyltoloxamine ›
Showing the 60 most looked-up of 1,612 medications checked with no known interaction — see the full Oregon Grape list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Diphenhydramine Hydrochloride, Naproxen Sodium Is Linked to Lower Levels of One Nutrient
Natural Medicines records Diphenhydramine Hydrochloride, Naproxen Sodium as a medicine that can lower these. This is not an interaction with Oregon Grape — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Diphenhydramine Hydrochloride, Naproxen Sodium nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Oregon Grape and Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions
Can you take Oregon Grape with Diphenhydramine Hydrochloride, Naproxen Sodium?
Why are there 3 interactions listed for Oregon Grape and Diphenhydramine Hydrochloride, Naproxen Sodium?
How serious is the Oregon Grape and Diphenhydramine Hydrochloride, Naproxen Sodium interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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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.