Sage + Diphenhydramine Hydrochloride, Naproxen Sodium
Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.
Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 drug categories that Sage can interact with; the most serious is rated moderate. Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.
Read the full interaction reportSage and Diphenhydramine Hydrochloride, Naproxen Sodium
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Sage interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 of those categories, so it can interact with Sage 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 Sage interacts with.
Some constituents of sage have CNS depressant activity.
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 pairs naproxen (a pain reliever) with diphenhydramine, a sedating antihistamine that's meant to help you sleep. The concern here is all about the diphenhydramine side. Some compounds in sage have shown mild calming, CNS-depressant activity in lab studies, so in theory, adding sage on top could deepen the drowsiness this product already causes. That might mean feeling extra groggy, foggy, dizzy, or having a harder time waking up.
I'll be honest: this is theoretical, based only on test-tube and animal data, so I wouldn't lose sleep over a sprinkle of sage in your cooking. Concentrated sage extracts or the essential oil are a bigger question. If you take those regularly, mention it to your pharmacist or doctor first.
- Perry NS, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 2003;75:651-9.. PubMed
CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES
2 of 3Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9. So far, this interaction has not been reported in humans.
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 combines naproxen (an anti-inflammatory pain reliever) with diphenhydramine (a sedating antihistamine). Here the part that matters is the naproxen, which your body partly clears using a liver enzyme called CYP2C9. In lab dish studies, sage has slowed that enzyme down. In theory, that could let naproxen build up a bit and nudge up its usual side effects, things like stomach upset, heartburn, or a higher risk of stomach irritation or bleeding.
I want to be honest about the strength of this: it has only been seen in test tube studies, never reported in real people, so it is more of a caution than a proven problem. A little sage in cooking is very unlikely to matter. Concentrated sage extracts or oil are where I would be more careful. If you use either regularly, just check with your pharmacist or doctor.
- Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
ANTICHOLINERGIC DRUGS
3 of 3Diphenhydramine Hydrochloride, Naproxen Sodium also falls under ANTICHOLINERGIC DRUGS.
In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels.
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 combines naproxen (a pain reliever) with diphenhydramine, the same sleep-aid antihistamine found in Benadryl. Diphenhydramine works partly by blocking a brain chemical called acetylcholine, which is what makes you drowsy. Here's the wrinkle: lab studies suggest sage may do the opposite and nudge acetylcholine levels up. In theory, that could slightly push back against the diphenhydramine and make it a little less effective at helping you fall asleep.
The honest truth is this is only seen in test-tube research, not in real people, so it may not amount to much. Food amounts of sage in cooking are very unlikely to matter. If you're using concentrated sage extracts or essential oil, just mention it to your pharmacist or doctor first.
- Orhan, I., Kartal, M., Kan, Y., and Sener, B. Activity of essential oils and individual components against acetyl- and butyrylcholinesterase. Z.Naturforsch.C. 2008;63(7-8):547-553.
- Perry, N. S., Houghton, P. J., Theobald, A., Jenner, P., and Perry, E. K. In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 2000;52(7):895-902.
- Savelev, S. U., Okello, E. J., and Perry, E. K. Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res 2004;18(4):315-324.
- Kennedy, D. O., Pace, S., Haskell, C., Okello, E. J., Milne, A., and Scholey, A. B. Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology 2006;31(4):84 PubMed
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.
Sage Also Interacts With Other Medications
Sage has 1,295 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 Sage
We haven’t checked that one against Sage yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Sage. Pick one to open its full report.
See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium
This page covers Sage 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 Sage as Part of a Dietary Supplement Product? Check It for Interactions
We hold 718 real supplement products containing Sage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sage. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Sage — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Sage 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.
#229 of 1,452 supplements looked up here in the last 7 days
#189 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 Sage
What is Sage?
- Sore throat and mouth irritation
- Digestive upset
- Excessive sweating
- Memory and thinking
- Menopause symptoms (hot flashes)
- General antioxidant support
Sage is a common kitchen herb that is generally safe in food amounts and is traditionally used for sore throats, digestion, sweating, and memory. Some early research is encouraging for sore throat and menopausal hot flashes, but most uses are not well proven. Concentrated extracts and the essential oil should be used carefully because high doses contain a compound called thujone, which can be harmful.
Other Drugs & Sage
Browse every other medication we’ve checked against Sage — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,295 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Diphenhydramine ›
- Hydrocortisone ›
- Insulin (rdna) ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Glycopyrrolate ›
- Insulin (pork) ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Insulin (human) ›
- Ipratropium ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Procainamide ›
- Trimipramine ›
- Acetaminophen ›
Showing 60 of 1,295 moderate interactions — see all 1,295 on the Sage page.
No interaction 1,534 drugs checked — show the list
We also checked Sage against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Rosuvastatin ›
- Aspirin ›
- Escitalopram ›
- Isotretinoin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Levothyroxine, Liothyronine ›
- Methotrexate ›
- Amoxicillin ›
- Bupropion ›
- Azithromycin ›
- Bendamustine ›
- Acyclovir ›
- Methylene Blue ›
- Ciprofloxacin ›
- Amoxicillin, Clavulanate Potassium ›
- Acetylsalicylic Acid ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Cephalexin ›
- Ezetimibe ›
- Cyclopentolate ›
- Levodopa ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Aspirin, Butalbital ›
- 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) ›
- Aminolevulinic Acid Hydrochloride ›
- Peginterferon Alfa-2a, Ribavirin ›
- Articaine, Epinephrine ›
- Alpha-1 Proteinase Inhibitor ›
- Sodium Bicarbonate (otc Drug) ›
- Cytomegalovirus Immune Globulin ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Tubocurarine ›
- Acenocoumarol ›
- Flutemetamol F-18 ›
- Dexmethylphenidate ›
- Imipenem, Cilastatin, Relebactam ›
- Hydroxychloroquine ›
- Cefaclor ›
- Dihydroxyaluminum Sodium Carbonate ›
- Bleomycin ›
- Lonapegsomatropin-tcgd ›
- Measles, Mumps, Rubella Virus Live ›
- Rosuvastatin Calcium, Ezetimibe ›
Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage 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 Sage — 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 Sage and Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions
Can you take Sage with Diphenhydramine Hydrochloride, Naproxen Sodium?
Why are there 3 interactions listed for Sage and Diphenhydramine Hydrochloride, Naproxen Sodium?
How serious is the Sage 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.