Drug & supplement interaction

Sage + Acetaminophen, Codeine, Doxylamine

Acetaminophen, Codeine, Doxylamine brand name: Mersyndol.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Codeine, Doxylamine falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sage and Acetaminophen, Codeine, Doxylamine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Sage interacts with whole categories of medication. Acetaminophen, Codeine, Doxylamine falls into 4 of those categories, so it can interact with Sage in 4 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 4

Why this applies to Acetaminophen, Codeine, Doxylamine

Acetaminophen, Codeine, Doxylamine 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

Mersyndol already has two ingredients that make you drowsy: the codeine and the doxylamine (an antihistamine). The concern here is simple. Some compounds in sage may have their own mild calming, sedative-type activity, so stacking concentrated sage on top of this medicine could, in theory, leave you extra sleepy, foggy, dizzy, or slow to react.

I want to be honest about the strength of this: it comes from lab and animal studies, not from people, so it's more theoretical than proven. A little sage in your cooking is very unlikely to matter. Concentrated sage extracts or the essential oil are where I'd be more cautious. If you take Mersyndol regularly and want to add a sage supplement, run it by your pharmacist or doctor first, and don't drive until you know how the combo affects you.

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 4

Acetaminophen, Codeine, Doxylamine 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 Mersyndol: the codeine part is a prodrug. Your body has to convert it into morphine using an enzyme called CYP2D6 before it does much for pain. Lab studies (not real people yet) hint that sage may slow that same enzyme down. If it did, less codeine would turn into morphine, so you might actually get weaker pain relief rather than more.

The good news is this is only theoretical, based on test-tube work, and food amounts of sage in cooking are very unlikely to matter. Concentrated sage extracts or the essential oil are where I'd be more cautious. If you take Mersyndol regularly and want to use sage supplements, just run it by your pharmacist or doctor first.

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

ANTICHOLINERGIC DRUGS

3 of 4

Acetaminophen, Codeine, Doxylamine 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

The piece of Mersyndol we're focused on here is the doxylamine, which is an antihistamine that works partly by blocking acetylcholine, a messenger chemical in your body. That's what gives doxylamine its drowsy, drying effects (sleepiness, dry mouth, a bit of constipation). In lab tests, sage seems to do the opposite, nudging acetylcholine levels up a little. So in theory, concentrated sage could slightly blunt the effects of the doxylamine portion.

I want to be honest, though: this is only test-tube evidence, and it's considered a possible, mild concern. Everyday cooking amounts of sage almost certainly won't matter. The codeine and acetaminophen parts aren't really involved here. If you're using strong sage extracts or the essential oil regularly, just mention it to your pharmacist or doctor first.

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

4 of 4

Acetaminophen, Codeine, Doxylamine 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 for Mersyndol (which combines acetaminophen, codeine, and the antihistamine doxylamine) alongside sage. The concern on file is theoretical and comes only from animal studies. In those studies, drinking sage tea seemed to rev up a liver enzyme called CYP2E1. That same enzyme is one of the routes your body uses to break down acetaminophen.

Why does that matter? When acetaminophen goes through CYP2E1, a small amount turns into a toxic byproduct that's normally cleared safely. In theory, speeding up that pathway could nudge more toward that harmful byproduct, which is a liver concern, especially with regular or higher acetaminophen doses. This has never actually been reported in people, and a little sage in cooking is very unlikely to matter. Concentrated sage extracts or strong sage tea taken often are the bigger question mark. If you use those regularly, check in with your pharmacist or doctor.

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, Doxylamine one above is among them. If you take anything else, check it against the full list below.

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, Doxylamine

This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Codeine, Doxylamine page lists 261 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 · 208 moderate · 42 minor.

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

“Mersyndol pairs acetaminophen with codeine and doxylamine, two sedating drugs in one tablet, so I read its interaction list with genuine vigilance. Of the 261 supplements and herbs on file, the biggest hazard is anything else that slows the brain: 78 ingredients add sedation, and that group holds several of the 11 major-rated entries,…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Codeine, Doxylamine 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, Doxylamine 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, Doxylamine 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, Doxylamine
Steady interest

#1,582 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
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
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

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Pharmacist Counseling Corner

Taking Sage and Acetaminophen, Codeine, Doxylamine Together: Common Questions

Can you take Sage with Acetaminophen, Codeine, Doxylamine?
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 4 interactions listed for Sage and Acetaminophen, Codeine, Doxylamine?
Acetaminophen, Codeine, Doxylamine 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, Doxylamine 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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