Drug & supplement interaction

Oregon Grape + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

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

Benzhydrocodone, Acetaminophen falls into 3 drug categories that Oregon Grape can interact with; the most serious is rated moderate. Theoretically, Oregon grape might increase the sedative 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

Oregon Grape and Benzhydrocodone, Acetaminophen

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Oregon Grape interacts with whole categories of medication. Benzhydrocodone, Acetaminophen falls into 3 of those categories, so it can interact with Oregon Grape 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 Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen falls under CNS DEPRESSANTS — the group Oregon Grape interacts with.

Theoretically, Oregon grape might increase the sedative effects of CNS depressants.
Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects.
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. Apadaz pairs an opioid (benzhydrocodone) with acetaminophen, and opioids already slow down your brain and body. Oregon grape contains berberine, and in animal studies berberine showed mild calming, sedative-type effects. Put the two together and the worry is that they could stack on top of each other, leaving you extra drowsy, foggy, dizzy, or making your breathing slower than it should be.

I want to be honest about how strong this evidence is: it's theoretical, based on lab and animal research, not real-world human reports. So this isn't a reason to panic. Still, since this is a narcotic, it's smart to play it safe. Talk with your pharmacist or doctor before combining them, and don't start or stop anything on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  2. Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
  3. Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
  4. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (CYP2D6).
Severity Moderate Likelihood Possible Evidence B

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 something worth knowing about Apadaz. The benzhydrocodone part is actually a prodrug, meaning your body has to convert it into hydrocodone before it can ease your pain. That conversion relies heavily on an enzyme called CYP2D6, the same enzyme that berberine in Oregon grape may slow down.

So in theory, if Oregon grape blocks that enzyme, your body might make less active hydrocodone, which could mean weaker pain relief than you expected. The honest truth is this is mostly theoretical, based on lab work and limited human data, so we can't be sure how much it matters in real life. Casual amounts likely matter less than concentrated supplements. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  2. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  3. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Benzhydrocodone, Acetaminophen also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (CYP3A4).
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 thing to know about Apadaz: the benzhydrocodone part is a prodrug. Your body has to convert it into hydrocodone before it actually relieves pain. Hydrocodone is then handled by liver enzymes, including CYP3A4. The berberine in Oregon grape may modestly slow down CYP3A4.

In practice, that could let active opioid levels run a little higher than expected, which means more chance of drowsiness, dizziness, constipation, nausea, or slowed breathing. I want to be honest, though: this concern is theoretical, based mostly on lab work, not strong human studies. Culinary brushes with the plant likely don't matter, but concentrated berberine supplements are a bigger question mark. Please check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  2. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  3. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  4. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed

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

Oregon Grape Also Interacts With Other Medications

Oregon Grape has 1,217 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.

Moderate 1,217 No known interaction 1,613 (incl. Benzhydrocodone, Acetaminophen)
Taking anything else?

Check Another of Your Medications Against Oregon Grape

Covers the 2,830 medications we’ve checked against Oregon Grape. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Benzhydrocodone, Acetaminophen

This page covers Oregon Grape 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.

Open the Benzhydrocodone, Acetaminophen interaction page

One more smart check

Taking Oregon Grape as Part of a Dietary Supplement Product? Check It for Interactions

We hold 740 real supplement products containing Oregon Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Oregon Grape. Your product may carry other ingredients that interact with Benzhydrocodone, Acetaminophen too, on top of Oregon Grape — 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 Oregon Grape 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.

Supplement Oregon Grape
Top 25%

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,159 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 Oregon Grape

What is Oregon Grape?

Oregon Grape
  • Psoriasis (topical)
  • Eczema and other skin conditions
  • Digestive upset
  • Mild skin infections
  • General 'detox' or tonic use

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that may slightly ease psoriasis; evidence for other uses is limited. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Oregon Grape monograph & all interactions
Medication

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.

See full Benzhydrocodone and Acetaminophen drug information
Keep checking

Other Drugs & Oregon Grape

Browse every other medication we’ve checked against Oregon Grape — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
1,217Moderate
0Minor
1,612No known interaction
1,217 Moderate 1,612 No interaction
Moderate

1,217 interactions

Showing 60 of 1,217 moderate interactions — see all 1,217 on the Oregon Grape page.

No interaction 1,612 drugs checked — show the list

We also checked Oregon Grape against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,612 medications checked with no known interaction — see the full Oregon Grape list.

See the full Oregon Grape interactions page
See every supplement checked against Benzhydrocodone, Acetaminophen, 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
Oregon Grape monograph › Uses, safety, and every drug interaction in one place Benzhydrocodone, Acetaminophen supplement interactions › Every supplement checked against Benzhydrocodone, Acetaminophen, ranked by severity Benzhydrocodone and Acetaminophen drug information › The full plain-English guide to this medication 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 Oregon Grape and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Oregon Grape with Benzhydrocodone, Acetaminophen?
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 Oregon Grape and Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen belongs to more than one drug category, and Oregon Grape 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 Oregon Grape and Benzhydrocodone, Acetaminophen 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

Still Have a Question About Benzhydrocodone, Acetaminophen and Oregon Grape?

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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.