Sage + Tramadol, Acetaminophen
Tramadol, Acetaminophen brand name: Tramacet.
Tramadol, Acetaminophen 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 reportSage and Tramadol, Acetaminophen
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. Tramadol, Acetaminophen 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).
CNS DEPRESSANTS
1 of 4Why this applies to Tramadol, Acetaminophen
Tramadol, Acetaminophen 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.
Here's the gist with Tramacet (which combines tramadol and acetaminophen). The tramadol part already works on your brain and can make you feel drowsy, dizzy, or foggy. Some natural compounds in sage may have a mild calming, sedative-type effect of their own, so in theory pairing the two could add up and leave you more sleepy, lightheaded, or slow to react than usual.
I'll be honest though: this concern comes only from lab and animal studies, not from real patients, so it's a theoretical worry, not a proven one. Sprinkling sage on dinner is very unlikely to matter. Concentrated sage extracts or the essential oil are where I'd be more cautious. If you use those regularly, just give your pharmacist or doctor a quick heads-up.
- 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 2D6 (CYP2D6) SUBSTRATES
2 of 4Tramadol, Acetaminophen also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6. 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.
Here's the wrinkle with this combo. Tramadol is partly a prodrug, meaning your liver uses an enzyme called CYP2D6 to turn it into its stronger pain-relieving form. Lab studies suggest sage may block that same enzyme. If that happens, you could actually get less pain relief from the tramadol part, because your body can't convert as much of it. The acetaminophen side isn't really affected here.
Now, the good news: this is only a test-tube finding, and it has never been reported in real people. Normal cooking amounts of sage almost certainly won't matter. Concentrated sage extracts or sage oil are where I'd be more cautious. If you take those regularly, just run it by your pharmacist or doctor first.
- 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
- 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.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 4Tramadol, Acetaminophen also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. 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.
Here's the gist with Tramacet (tramadol plus acetaminophen) and sage. Lab studies hint that sage may slow down a liver enzyme called CYP3A4, which is one of the pathways your body uses to clear tramadol. If that enzyme is blocked, a bit more tramadol could linger in your system. In theory that might mean stronger opioid effects like drowsiness, dizziness, nausea, constipation, or slowed breathing.
That said, this is purely a test-tube finding and has never actually been seen in people, so I wouldn't lose sleep over it. Sage in normal cooking amounts is very unlikely to matter; concentrated extracts or the essential oil are where I'd be more cautious. If you take sage supplements regularly, just mention it to 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
- Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
4 of 4Tramadol, Acetaminophen also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
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.
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 gist with Tramacet (tramadol plus acetaminophen) and sage. This is a theoretical interaction based only on animal research, where sage tea seemed to ramp up an enzyme called CYP2E1. Nothing like this has actually been reported in people, so I don't want you to lose sleep over it.
The piece worth knowing involves acetaminophen (Tylenol). CYP2E1 is the pathway that turns a small portion of acetaminophen into a byproduct that can stress the liver. If sage truly sped up that enzyme, it could theoretically nudge a bit more of acetaminophen down that route. In practice, normal cooking amounts of sage are no concern. If you're using concentrated sage extracts or essential oil regularly, just give your pharmacist or doctor a heads-up.
- 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.
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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen
This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol, Acetaminophen page lists 280 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: 12 major · 224 moderate · 44 minor.
From our pharmacist’s overview on the Tramadol, Acetaminophen page
“The combinations I worry about most with tramadol and acetaminophen (Tramacet) involve anything that deepens drowsiness or strains the liver. Tramadol is an opioid, so sedating supplements like kava, along with alcohol in any form, can slow breathing on top of adding sleepiness, which is why this list deserves genuine care rather than…”
Reviewed by 2 · Jul 18, 2026
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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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.
#263 of 1,452 supplements looked up here in the last 7 days
#415 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 ›
- Aspirin ›
- Rosuvastatin ›
- Escitalopram ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Bupropion ›
- Amoxicillin ›
- Acyclovir ›
- Bendamustine ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Levothyroxine Sodium ›
- Dexmethylphenidate ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Lenvatinib ›
- Phenylephrine ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Bentoquatam ›
- Dirithromycin ›
- Tenecteplase ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Azelaic Acid ›
- Dextrothyroxine ›
- Triptorelin ›
- Lomustine ›
- Acetylsalicylic Acid ›
- Tocainide ›
- Pizotifen ›
- Rocuronium ›
- Succimer ›
- Mitomycin C ›
- Halothane ›
- Gestodene ›
- Chenodiol ›
- Desflurane ›
- Niacin (prescription Drug) ›
- Metronidazole ›
- Caspofungin ›
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
Tramadol, Acetaminophen Is Linked to Lower Levels of One Nutrient
Natural Medicines records Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen Together: Common Questions
Can you take Sage with Tramadol, Acetaminophen?
Why are there 4 interactions listed for Sage and Tramadol, Acetaminophen?
How serious is the Sage and Tramadol, Acetaminophen interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Tramadol, Acetaminophen and Sage?
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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.