Drug & supplement interaction

Phellodendron + Aspirin, Caffeine, Phenacetin, Propoxyphene

Aspirin, Caffeine, Phenacetin, Propoxyphene brand name: Margesic Comp. 65.

Moderate Interaction
The bottom line Moderate

Aspirin, Caffeine, Phenacetin, Propoxyphene falls into 4 drug categories that Phellodendron can interact with; the most serious is rated moderate. Theoretically, phellodendron might increase the sedative effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Phellodendron and Aspirin, Caffeine, Phenacetin, Propoxyphene

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Phellodendron interacts with whole categories of medication. Aspirin, Caffeine, Phenacetin, Propoxyphene falls into 4 of those categories, so it can interact with Phellodendron in 4 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 4

Why this applies to Aspirin, Caffeine, Phenacetin, Propoxyphene

Aspirin, Caffeine, Phenacetin, Propoxyphene falls under CNS DEPRESSANTS — the group Phellodendron interacts with.

Theoretically, phellodendron might increase the sedative effects of CNS depressants.
Phellodendron contains berberine. Animal research suggests that berberine may have sedative effects. Theoretically, phellodendron might also have CNS depressants 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 product contains propoxyphene, an opioid pain reliever that can make you feel drowsy or relaxed, plus aspirin and caffeine. The concern here is fairly simple: phellodendron contains berberine, and in animal studies berberine has shown mild sedative effects. So in theory, pairing it with the propoxyphene part could add to that sleepy, slowed-down feeling, leading to more drowsiness, dizziness, or trouble concentrating.

I want to be honest about the strength of this: it is theoretical, based on lab and animal work, not solid human studies. For most people this won't be a big deal, but if you notice extra grogginess, take it easy with driving and check in with your pharmacist or doctor before combining them.

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 4

Aspirin, Caffeine, Phenacetin, Propoxyphene also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP2D6.
Phellodendron contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, phellodendron might also inhibit CYP2D6.
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

In this combination pill, the ingredient that matters most for this interaction is propoxyphene, an opioid pain reliever that the body partly handles through a liver enzyme called CYP2D6. Phellodendron contains berberine, which lab and early human studies suggest can slow that same enzyme down. In theory, that could let propoxyphene build up a bit, which might bump up its effects: more drowsiness, dizziness, nausea, constipation, or feeling foggy.

I want to be honest that this is a theoretical concern based on how these compounds behave, not something proven in real patients. The aspirin and caffeine pieces aren't the main players here. Still, because propoxyphene is a sedating opioid, I'd run this past your pharmacist or doctor before combining them rather than guessing.

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 4

Aspirin, Caffeine, Phenacetin, Propoxyphene also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP3A4.
Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, phellodendron might also inhibit 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

This combination pill packs several ingredients, but the one that matters most here is propoxyphene, an opioid pain reliever that your liver processes using an enzyme called CYP3A4. Phellodendron contains berberine, which lab and early human studies suggest can mildly slow that same enzyme down. In theory, that could let propoxyphene linger a bit longer in your body, nudging up its effects, things like extra drowsiness, dizziness, nausea, or constipation.

I want to be honest with you though: this is a theoretical concern based on how the chemistry works, not on real cases. Concentrated supplement doses are more likely to matter than a sip of herbal tea. Since this product is fairly potent, please check with your pharmacist or doctor before pairing it with phellodendron.

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
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

4 of 4

Aspirin, Caffeine, Phenacetin, Propoxyphene also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, phellodendron might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Phellodendron contains berberine. In vitro and in vivo research suggest that berberine can inhibit platelet aggregation. Theoretically, phellodendron might also inhibit platelet aggregation.
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 product includes aspirin, which is the part that matters here. Aspirin already thins the blood by blocking platelets from clumping together. Phellodendron contains berberine, and early lab and animal research hints that it may also slow platelet activity. Put the two together and, in theory, you could be a little more prone to bruising, nosebleeds, bleeding gums, or stomach upset from the aspirin.

I want to be honest with you: this is a theoretical concern based only on test-tube and animal studies, not real-world human cases, so the actual risk is likely small. Still, since both nudge in the same direction, it is worth a quick chat with your pharmacist or doctor before pairing them, especially if you already bruise easily or take other blood thinners.

References
  1. Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
  2. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.

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

Phellodendron Also Interacts With Other Medications

Phellodendron has 1,159 moderate known drug interactions in our database — the Aspirin, Caffeine, Phenacetin, Propoxyphene one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Phellodendron

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Phenacetin, Propoxyphene

This page covers Phellodendron only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Phenacetin, Propoxyphene page lists 414 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 Danshen (major).

By severity: 17 major · 350 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Phenacetin, Propoxyphene page

“Margesic Comp. 65 packs four drugs into one tablet, aspirin, caffeine, phenacetin, and the sedating opioid propoxyphene, which is why 414 supplement ingredients appear on this page and why I would slow down before adding any of them.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Phenacetin, Propoxyphene interaction page

One more smart check

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

We hold 393 real supplement products containing Phellodendron, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phellodendron. Your product may carry other ingredients that interact with Aspirin, Caffeine, Phenacetin, Propoxyphene too, on top of Phellodendron — 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 Phellodendron and Aspirin, Caffeine, Phenacetin, Propoxyphene 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 Phellodendron
Top 25%

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

29 days ago today
Medication Aspirin, Caffeine, Phenacetin, Propoxyphene
Steady interest

#2,649 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 Phellodendron

What is Phellodendron?

Phellodendron
  • Digestive complaints and diarrhea
  • Inflammation and joint discomfort
  • Stress and weight management (in combination products)
  • Skin conditions (topical, traditional)
  • Antimicrobial support

Phellodendron is a traditional Chinese medicine bark (Huang Bai) that contains berberine and other plant compounds with antimicrobial and anti-inflammatory activity in lab studies. Human evidence for most uses is limited, and it is often sold in combination with other herbs, making its individual effects hard to judge. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Phellodendron monograph & all interactions
Keep checking

Other Drugs & Phellodendron

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

0Major
1,159Moderate
0Minor
1,670No known interaction
Moderate

1,159 interactions

Showing 60 of 1,159 moderate interactions — see all 1,159 on the Phellodendron page.

No interaction 1,670 drugs checked — show the list
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
Pharmacist Counseling Corner

Taking Phellodendron and Aspirin, Caffeine, Phenacetin, Propoxyphene Together: Common Questions

Can you take Phellodendron with Aspirin, Caffeine, Phenacetin, Propoxyphene?
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 4 interactions listed for Phellodendron and Aspirin, Caffeine, Phenacetin, Propoxyphene?
Aspirin, Caffeine, Phenacetin, Propoxyphene belongs to more than one drug category, and Phellodendron 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 Phellodendron and Aspirin, Caffeine, Phenacetin, Propoxyphene 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.