Sage + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 5 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
These two interact in 5 distinct ways. Each one is explained separately below.
Why Are There 5 Interactions?
Sage interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 5 of those categories, so it can interact with Sage in 5 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 5Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
This combination product (Hycomine Compound) already has two ingredients that can make you drowsy: hydrocodone, an opioid pain reliever, and chlorpheniramine, a sedating antihistamine. The concern here is that some natural compounds in sage may have mild calming or sedative activity of their own. Stacked on top of these medicines, that could in theory deepen the drowsiness, leaving you more groggy, foggy, or unsteady than usual.
I want to be honest that this is a theoretical worry, based only on lab and animal studies, not real patient reports. Sprinkling sage on your dinner is very unlikely to matter. Concentrated sage extracts or the essential oil are where I'd be more cautious. If you take a sage supplement regularly, just run it by 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 2D6 (CYP2D6) SUBSTRATES
2 of 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
This combo product (Hycomine Compound) includes hydrocodone, an opioid that your body activates partly through an enzyme called CYP2D6. In lab studies only, sage extracts have shown they might slow this enzyme down. If that happened in people, it could change how hydrocodone is converted to its more active form. The direction is a bit unpredictable since hydrocodone is partly a prodrug, so you might notice slightly different pain relief, or more typical opioid effects like drowsiness, dizziness, constipation, or nausea.
Here is the reassuring part: this has only been seen in a test tube, never reported in real patients, and everyday cooking amounts of sage are very unlikely to matter. Concentrated sage extracts or essential oil are the bigger question. If you use 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 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
This combination product (sold as Hycomine Compound) contains several ingredients, and the one most worth thinking about here is hydrocodone, the opioid. Hydrocodone is partly handled by a liver enzyme called CYP3A4. In lab studies, water-based sage extracts seem to slow that enzyme down a bit. In theory, that could let hydrocodone build up slightly, which might add to drowsiness, dizziness, slowed breathing, or constipation.
Here is the reassuring part: this is only test-tube evidence, and it has never actually been reported in people. Everyday cooking amounts of sage are very unlikely to matter. Concentrated sage extracts or sage essential oil are a different story. If you use those regularly, just mention it to your pharmacist or doctor before mixing them with this medicine.
- 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.
ANTICHOLINERGIC DRUGS
4 of 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
In this combo product, the piece that matters for sage is chlorpheniramine, an older antihistamine that works partly by blocking acetylcholine, a nerve-signaling chemical. That's what makes it dry up a runny nose, but also why it can cause dry mouth, drowsiness, blurred vision, and constipation.
The idea here is that sage may raise acetylcholine levels, which could slightly push back against chlorpheniramine's drying action. In plain terms, sage might make this part of the medicine work a little less. I want to be honest though: this comes only from lab studies, not from people, so it's theoretical and likely small, especially with sage used as a cooking herb. Concentrated sage extracts are more of an unknown. If you're using a strong sage supplement regularly, just run it by your pharmacist or doctor.
- 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
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
5 of 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
This combo product (Hycomine Compound) contains acetaminophen (Tylenol), and that's the piece that connects to sage here. Acetaminophen is partly handled by a liver enzyme called CYP2E1. In animal studies, drinking sage tea seemed to rev up this enzyme. The worry is that a faster enzyme could shift more acetaminophen down a pathway that produces a liver-stressing byproduct, especially with regular or high doses.
Here's the honest part: this is only theoretical and based on lab and animal work. It has never been reported in people, so a little sage in your cooking is very unlikely to cause trouble. Concentrated sage extracts or essential oil are a different story. If you take this medicine often or use strong sage supplements, just check with your pharmacist or doctor first.
- 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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 Ephedra (major).
By severity: 17 major · 276 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page
“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
#260 of 1,452 supplements looked up here in the last 7 days
#467 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 ›
- Valacyclovir ›
- Docusate ›
- Hydroxyurea ›
- Sumatriptan ›
- Acyclovir ›
- Bupropion ›
- Amoxicillin ›
- Bendamustine ›
- Methotrexate ›
- Isotretinoin ›
- Azithromycin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Mitomycin ›
- Cefaclor ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Ezetimibe ›
- Levodopa ›
- Vancomycin ›
- Phenylephrine ›
- Dirithromycin ›
- Lenvatinib ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Bentoquatam ›
- Tenecteplase ›
- Amoxicillin, Clavulanate Potassium ›
- Hydroxychloroquine ›
- Dextrothyroxine ›
- Triptorelin ›
- Lomustine ›
- Acetylsalicylic Acid ›
- Succimer ›
- Tocainide ›
- Rocuronium ›
- Halothane ›
- Mitomycin C ›
- Pizotifen ›
- Gestodene ›
- Chenodiol ›
- Niacin (prescription Drug) ›
- Desflurane ›
- Cabergoline ›
- Famotidine ›
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
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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:
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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Sage with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 5 interactions listed for Sage and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Sage and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Sage?
Our pharmacists answer your medication & supplement questions — free.
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.