Sage + Benzhydrocodone, Acetaminophen
Benzhydrocodone, Acetaminophen brand name: Apadaz.
Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen
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. Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen
Benzhydrocodone, 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 Apadaz (benzhydrocodone and acetaminophen): it's an opioid pain reliever, so it already slows down your brain and nervous system. That can mean drowsiness, slowed breathing, dizziness, or feeling foggy. Some natural compounds in sage may have a mild calming, sedative-type effect of their own. The worry is that stacking the two could add up and leave you more sleepy or slowed down than expected.
I want to be honest about the strength here: this is a theoretical concern based on lab and animal data, not real patient cases. Cooking with sage almost certainly won't matter. Concentrated sage extracts or essential oil are where I'd be more cautious. Since this is an opioid, please run any sage supplement 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 5Benzhydrocodone, 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 something worth knowing about Apadaz (benzhydrocodone with acetaminophen). The benzhydrocodone part is a prodrug, meaning your body has to convert it into hydrocodone before it works. From there, the enzyme CYP2D6 turns some of that into an even stronger painkiller. Lab studies hint that sage might block CYP2D6.
If that blocking happened in real life, it could actually reduce the conversion to the strongest form, so you might get a bit less pain relief. The flip side is that more hydrocodone could linger, possibly adding to drowsiness or constipation. Honestly, this is only based on test-tube data and has never been seen in people, and cooking with sage is a non-issue. Concentrated sage extracts or oils are where I'd pause. Check with your pharmacist if you use those.
- 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 5Benzhydrocodone, 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 Apadaz (benzhydrocodone and acetaminophen): benzhydrocodone is a prodrug, meaning your body has to convert it into hydrocodone before it relieves pain. Lab studies hint that concentrated sage may block an enzyme called CYP3A4, which helps clear hydrocodone from your system. If that holds true in people, the opioid could linger a bit longer, possibly nudging up effects like drowsiness, dizziness, constipation, nausea, or slowed breathing.
I want to be honest: this is theoretical only, seen in test tubes, never confirmed in humans, and ordinary cooking amounts of sage almost certainly won't matter. Still, if you're using sage extracts, oils, or supplements, mention it to your pharmacist or doctor before mixing the two.
- 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 5Benzhydrocodone, Acetaminophen 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.
Here's the honest take: this particular interaction is mostly theoretical and comes from lab studies, not from people. The idea is that sage may raise levels of a brain chemical called acetylcholine by blocking the enzyme that breaks it down. That could, in theory, work against medicines that have anticholinergic (acetylcholine-blocking) effects. Apadaz (benzhydrocodone with acetaminophen) is really an opioid pain reliever, and its anticholinergic action is fairly minor, so any real-world effect from sage is likely small.
What matters more in practice is that this is a strong opioid, with risks like drowsiness, slowed breathing, and constipation. Seasoning your food with sage won't be a problem. If you're using concentrated sage extracts or sage oil, just mention it to your pharmacist or doctor first.
- 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 5Benzhydrocodone, 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 Apadaz (benzhydrocodone with acetaminophen) and sage. One enzyme in your liver, called CYP2E1, helps process the acetaminophen part. In animal studies, sage tea seemed to ramp up that enzyme. The worry is mostly theoretical, and it has never actually been seen in people, so I wouldn't lose sleep over it.
The real-world concern is the acetaminophen, not the opioid. A more active CYP2E1 can nudge acetaminophen down a pathway that produces a liver-stressing byproduct, which matters more if you take a lot or drink alcohol. The opioid side (drowsiness, constipation, slowed breathing) isn't really driven by this enzyme. Sprinkling sage on food is no issue. If you use strong sage extracts daily, just mention it to your pharmacist.
- 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 Benzhydrocodone, 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 Benzhydrocodone, Acetaminophen
This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Benzhydrocodone, Acetaminophen page lists 299 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: 14 major · 239 moderate · 46 minor.
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 Benzhydrocodone, 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 Benzhydrocodone, 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.
#265 of 1,452 supplements looked up here in the last 7 days
#2,169 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.
About Benzhydrocodone and Acetaminophen
What Is Benzhydrocodone and Acetaminophen Used For?
Brand name: Apadaz
Apadaz is indicated for the short-term management of acute pain — up to 14 days — that is severe enough to require an opioid and for which non-opioid treatments have not worked or are not expected to work. It combines benzhydrocodone (a prodrug that converts to the opioid hydrocodone) with acetaminophen.
Because of serious risks including addiction, abuse, and misuse, Apadaz is reserved for patients who have not tolerated or have not gotten adequate relief from alternative pain treatments. It should not be used for an extended period of time unless the pain remains severe enough to require an opioid and alternatives remain inadequate.
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 ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Phenylephrine ›
- Vancomycin ›
- Lenvatinib ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Tenecteplase ›
- Azelaic Acid ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Pizotifen ›
- Tocainide ›
- Acetylsalicylic Acid ›
- Rocuronium ›
- Succimer ›
- Mitomycin C ›
- Halothane ›
- Chenodiol ›
- Desflurane ›
- Gestodene ›
- Niacin (prescription Drug) ›
- Cabergoline ›
- Metronidazole ›
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
Benzhydrocodone, Acetaminophen Is Linked to Lower Levels of One Nutrient
Natural Medicines records Benzhydrocodone, 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 Benzhydrocodone, 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 Benzhydrocodone, Acetaminophen Together: Common Questions
Can you take Sage with Benzhydrocodone, Acetaminophen?
Why are there 5 interactions listed for Sage and Benzhydrocodone, Acetaminophen?
How serious is the Sage and Benzhydrocodone, Acetaminophen interaction?
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.