Drug & supplement interaction

Phellodendron + Hydrocodone/Chlorpheniramine

Hydrocodone/Chlorpheniramine brand name: Tussionex.

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

Hydrocodone/Chlorpheniramine falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Phellodendron and Hydrocodone/Chlorpheniramine

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

Why Are There 3 Interactions?

Phellodendron interacts with whole categories of medication. Hydrocodone/Chlorpheniramine falls into 3 of those categories, so it can interact with Phellodendron 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 Hydrocodone/Chlorpheniramine

Hydrocodone/Chlorpheniramine 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

Here's the simple version. Tussionex already has two ingredients that make you sleepy: hydrocodone, an opioid, and chlorpheniramine, a sedating antihistamine. Phellodendron contains berberine, and in animal studies berberine seemed to have its own calming, sedative effect. So the worry is that stacking them could add up and leave you more drowsy than expected.

In real life that might look like extra grogginess, dizziness, trouble concentrating, or slowed, shallow breathing, which matters most with an opioid. To be fair, this is a theoretical concern based on lab and animal data, not strong human studies, so I don't want to scare you. Still, please check with your pharmacist or doctor before combining them, and don't drive until you know how you feel.

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

Hydrocodone/Chlorpheniramine 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

Here's the wrinkle with Tussionex (hydrocodone with chlorpheniramine): hydrocodone is partly a prodrug. Your body uses an enzyme called CYP2D6 to turn it into hydromorphone, which adds to its pain-relieving and cough-calming punch. Phellodendron contains berberine, which lab studies suggest can slow down that same enzyme. In theory, that could mean a little less of that active form, so the cough syrup might feel slightly weaker for some people.

I'll be honest, this is theoretical and based mostly on test-tube work, so it may not amount to much in real life. Hydrocodone still works without full CYP2D6 activity. The bigger thing I'd watch is that both this syrup and many herbal blends can cause drowsiness. Please check with your pharmacist or doctor before pairing 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

Hydrocodone/Chlorpheniramine 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

Here's the gist with Tussionex (hydrocodone and chlorpheniramine). The hydrocodone part is handled in part by a liver enzyme called CYP3A4. Phellodendron contains berberine, which lab and early human studies suggest can mildly slow that same enzyme. So in theory, this cough medicine could clear a bit more slowly and hang around longer.

If that happens, you might notice stronger opioid-type effects: extra drowsiness, dizziness, constipation, or slowed breathing, plus more of the antihistamine sleepiness and dry mouth. That said, this is theoretical, based mostly on pharmacology and lab work, not strong patient data. Still, since Tussionex already makes people sleepy, I'd run this combo by 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

Phellodendron Also Interacts With Other Medications

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

Moderate 1,159 No known interaction 1,671 (incl. Hydrocodone/Chlorpheniramine)
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 Hydrocodone/Chlorpheniramine

This page covers Phellodendron only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrocodone/Chlorpheniramine page lists 258 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 12 major · 204 moderate · 42 minor.

From our pharmacist’s overview on the Hydrocodone/Chlorpheniramine page

“Tussionex (hydrocodone with chlorpheniramine) pairs an opioid with a sedating antihistamine, so anything that deepens drowsiness or slows breathing is a genuine hazard, and 78 of the 258 supplements on file do exactly that. Alcohol in any form tops that group, and kava carries a major rating for the same reason.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine 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%

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

29 days ago today
Medication Hydrocodone/Chlorpheniramine
Steady interest

#1,737 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
1,159 Moderate 1,670 No 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

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

Showing the 60 most looked-up of 1,670 medications checked with no known interaction — see the full Phellodendron list.

See the full Phellodendron interactions page
See every supplement checked against Hydrocodone/Chlorpheniramine, 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
Phellodendron monograph › Uses, safety, and every drug interaction in one place Hydrocodone/Chlorpheniramine supplement interactions › Every supplement checked against Hydrocodone/Chlorpheniramine, 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 Phellodendron and Hydrocodone/Chlorpheniramine Together: Common Questions

Can you take Phellodendron with Hydrocodone/Chlorpheniramine?
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 Phellodendron and Hydrocodone/Chlorpheniramine?
Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine and Phellodendron?

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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.