Drug & supplement interaction

Sage + Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine brand names: Tylenol PM, Tylenol PM Ex Strength.

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

Acetaminophen, Diphenhydramine 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 report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sage and Acetaminophen, Diphenhydramine

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. Acetaminophen, Diphenhydramine 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).

Moderate

CNS DEPRESSANTS

1 of 3

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under CNS DEPRESSANTS — the group Sage interacts with.

Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.
Some constituents of sage have CNS depressant activity.
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

Tylenol PM pairs acetaminophen with diphenhydramine, an antihistamine that already makes most people drowsy. The thinking here is that certain compounds in sage may have a mild calming, sedative-like effect of their own. So in theory, layering concentrated sage on top of this product could add to the sleepiness, leaving you groggy, dizzy, foggy-headed, or extra unsteady on your feet the next morning.

I want to be honest about the evidence, though: this is based only on lab and animal studies, not real cases in people. A little sage in your cooking almost certainly won't matter. Strong sage extracts or the essential oil are where I'd be more cautious. If you take a concentrated sage supplement regularly, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
Moderate

ANTICHOLINERGIC DRUGS

2 of 3

Acetaminophen, Diphenhydramine also falls under ANTICHOLINERGIC DRUGS.

Theoretically, sage might decrease the clinical effects of anticholinergic drugs.
In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels.
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 gist with Tylenol PM. The part that matters for this interaction is the diphenhydramine (the same ingredient as Benadryl), which works by blocking a brain chemical called acetylcholine. That blocking action is what makes you drowsy and helps you sleep. In lab studies (not in people), sage appears to do the opposite by raising acetylcholine levels. So in theory, sage could slightly push back against the diphenhydramine and make it a touch less effective.

Honestly, this is very weak, test-tube evidence, so I wouldn't lose sleep over it. A little sage in your cooking won't matter at all. Concentrated sage extracts or essential oil are a different story and aren't worth gambling with. If you take this combo regularly and have questions, just run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.
  2. 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.
  3. 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.
  4. 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
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Diphenhydramine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.
Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1. 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

Here's the gist with Tylenol PM, which combines acetaminophen (the pain and fever reliever) and diphenhydramine (the sleepy antihistamine). The acetaminophen part is partly handled by a liver enzyme called CYP2E1. Animal studies hint that sage tea may speed that enzyme up. In theory, a faster enzyme could shift more acetaminophen down a pathway that creates a liver-stressing byproduct, especially at higher acetaminophen doses or with alcohol.

I want to be honest though: this is theoretical and comes only from animal research, never reported in people. Sage as a kitchen herb is very unlikely to matter. Concentrated sage extracts taken regularly are the bigger question mark. If you use either one often, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lima, C. F., Fernandes-Ferreira, M., and Pereira-Wilson, C. Drinking of Salvia officinalis tea increases CCl(4)-induced hepatotoxicity in mice. Food Chem.Toxicol. 2007;45(3):456-464.

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

Sage Also Interacts With Other Medications

Sage has 1,295 moderate known drug interactions in our database — the Acetaminophen, Diphenhydramine one above is among them. If you take anything else, check it against the full list below.

Moderate 1,295 No known interaction 1,535 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Sage

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Diphenhydramine

This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine page lists 254 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 Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 204 moderate · 39 minor.

Open the Acetaminophen, Diphenhydramine interaction page

One more smart check

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 Acetaminophen, Diphenhydramine 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:

How much people look this up

Where Sage and Acetaminophen, Diphenhydramine 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 Sage
Top 25%

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

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 10%

#222 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 Sage

What is Sage?

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.

Read the full Sage monograph & all interactions
Keep checking

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.

0Major
1,295Moderate
0Minor
1,534No known interaction
1,295 Moderate 1,534 No interaction
Moderate

1,295 interactions

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.

Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage list.

See the full Sage interactions page
See every supplement checked against Acetaminophen, Diphenhydramine, 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
Sage monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Diphenhydramine supplement interactions › Every supplement checked against Acetaminophen, Diphenhydramine, 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 Sage and Acetaminophen, Diphenhydramine Together: Common Questions

Can you take Sage with Acetaminophen, Diphenhydramine?
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 3 interactions listed for Sage and Acetaminophen, Diphenhydramine?
Acetaminophen, Diphenhydramine belongs to more than one drug category, and Sage 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 Sage and Acetaminophen, Diphenhydramine 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

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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.