Drug & supplement interaction

Sage + Acetaminophen, Codeine

Acetaminophen, Codeine brand names: Tylenol w/ Codeine, Tylenol No.3.

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

Acetaminophen, Codeine 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, Codeine

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, Codeine 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, Codeine

Acetaminophen, Codeine 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

Here's the simple version. The codeine in your Tylenol with Codeine is a calming, drowsy-type medicine, and some lab studies suggest a few of sage's natural compounds may also have a mild sedative effect. So in theory, pairing them could pile on extra sleepiness, dizziness, slowed breathing, or feeling foggy, especially when you first start the combo.

I want to be honest about the strength of this, though. It's based on lab and animal work, not real patient cases, and a little sage on your dinner is very unlikely to matter. The bigger question is concentrated sage extracts or sage essential oil taken in supplement form. If you're using those, run it by your pharmacist or doctor before mixing, and never adjust your pain medicine on your own.

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

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

Acetaminophen, Codeine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6. 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 wrinkle with this combo: the codeine in your Tylenol with Codeine is a prodrug. Your body has to convert it into morphine using a liver enzyme called CYP2D6 before you get any real pain relief. Lab studies hint that sage might slow that enzyme down. If that happened, less codeine would turn into morphine, so you could actually get weaker pain control, not stronger.

The good news is this is only test-tube evidence, and it has never been reported in real people. Normal cooking amounts of sage are very unlikely to matter. Concentrated sage extracts or the essential oil are a bigger question mark. If you use those regularly and feel your pain relief isn't working as well, check in with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Codeine 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 honest picture for your Tylenol with Codeine. The interaction on file deals with an enzyme called CYP2E1, and animal studies hint that sage tea might speed it up a little. The acetaminophen (Tylenol) part is the piece that connects here. When CYP2E1 runs faster, it can push more acetaminophen down a pathway that produces a liver-stressing byproduct, so in theory the concern is more about the liver than about pain relief.

I want to stress this is theoretical, seen only in lab and animal work, and not reported in people. Food amounts of sage in cooking are very unlikely to matter. Heavy use of concentrated sage extracts or essential oil is a different story. If you use sage supplements regularly, just mention it to your pharmacist or doctor.

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, Codeine 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, Codeine)
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, Codeine

This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Codeine page lists 240 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: 9 major · 191 moderate · 40 minor.

From our pharmacist’s overview on the Acetaminophen, Codeine page

“People usually take Tylenol No. 3 (acetaminophen with codeine) for short-term pain, often while still drinking wine with dinner or reaching for an herbal sleep aid.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Codeine 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, Codeine 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, Codeine 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%

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

29 days ago today
Medication Acetaminophen, Codeine
Top 5%

#59 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, Codeine, 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, Codeine supplement interactions › Every supplement checked against Acetaminophen, Codeine, 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, Codeine Together: Common Questions

Can you take Sage with Acetaminophen, Codeine?
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, Codeine?
Acetaminophen, Codeine 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, Codeine 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.