Drug & supplement interaction

Oregon Grape + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Acetaminophen, Butalbital, Codeine Phosphate falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Oregon Grape and Acetaminophen, Butalbital, Codeine Phosphate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Oregon Grape interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine Phosphate falls into 2 of those categories, so it can interact with Oregon Grape in 2 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 2

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate 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

This combination medicine already has two ingredients that can make you drowsy: butalbital (a barbiturate) and codeine (an opioid). The concern here is that Oregon grape contains berberine, which in animal studies showed mild calming, sedative-type effects. Stacked on top of your medicine, the worry is that it could add to the sleepiness.

I want to be honest about how thin this evidence is. It comes from lab and animal research, not people, so this is a theoretical concern rather than something proven. Still, with codeine and butalbital on board, it's reasonable to be cautious. Watch for extra drowsiness, dizziness, or feeling foggy, and don't drive until you know how you feel. Please run it by your pharmacist or doctor before combining them.

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 2

Acetaminophen, Butalbital, Codeine Phosphate 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 this combination. The codeine in your Phrenilin #3 is actually a prodrug, meaning it doesn't do much on its own. Your body has to convert it into morphine using an enzyme called CYP2D6, and that's where the pain relief comes from.

Oregon grape contains berberine, which lab studies and a little early human research suggest can slow down that same CYP2D6 enzyme. If the enzyme is blocked, less codeine gets turned into morphine, so you might get weaker pain relief than expected. Keep in mind this is mostly theoretical and based on lower-quality evidence, so it may not be a big deal for everyone. Still, before pairing them, check with your pharmacist or doctor.

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

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 Acetaminophen, Butalbital, Codeine Phosphate 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. Acetaminophen, Butalbital, Codeine Phosphate)
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 Acetaminophen, Butalbital, Codeine Phosphate

This page covers Oregon Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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).

Open the Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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%

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,621 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
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 Acetaminophen, Butalbital, Codeine Phosphate, 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 Acetaminophen, Butalbital, Codeine Phosphate supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, ranked by severity 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 Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Oregon Grape with Acetaminophen, Butalbital, Codeine Phosphate?
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 2 interactions listed for Oregon Grape and Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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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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.