Phellodendron + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 reportPhellodendron and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
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. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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).
CNS DEPRESSANTS
1 of 3Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CNS DEPRESSANTS — the group Phellodendron interacts with.
Phellodendron contains berberine. Animal research suggests that berberine may have sedative effects. Theoretically, phellodendron might also have CNS depressants effects.
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.
This combination product (Hycomine Compound) already carries two ingredients that can make you drowsy: hydrocodone, an opioid pain reliever, and chlorpheniramine, a sedating antihistamine. The concern here is simple stacking. In animal studies, the berberine in phellodendron showed mild sedative effects, so on paper it could add to that sleepiness.
If they pile up, you might feel more groggy, dizzy, or slowed down than usual, and breathing can be more depressed with opioids. I'll be honest though: this is a theoretical interaction based on lab and animal data, not strong human evidence, so I wouldn't panic. Just don't start phellodendron on your own. Run it by your pharmacist or doctor first, and avoid driving until you know how you feel.
- Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
- 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
- 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
- Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 3Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
Phellodendron contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, phellodendron might also inhibit CYP2D6.
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 wrinkle with this combination product: the hydrocodone piece is a prodrug. Your body uses an enzyme called CYP2D6 to convert it into a stronger painkiller. Berberine in phellodendron may gently block that same enzyme. So in theory, less hydrocodone could get switched into its active form, which might mean weaker pain relief than you'd expect.
On the flip side, the chlorpheniramine (an antihistamine) is also handled partly by CYP2D6, so it could build up a little and add to drowsiness or dry mouth. Keep in mind this is theoretical, based on lab work, not strong human studies, so the real-world effect may be small. Before combining them, just run it by your pharmacist or doctor.
- 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
- 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
- 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
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 3Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, phellodendron might also inhibit CYP3A4.
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.
This combination cold and pain product, sold as Hycomine Compound, includes hydrocodone, which your body partly processes through a liver enzyme called CYP3A4. The thinking here is that the berberine in Phellodendron may gently slow that enzyme down. If hydrocodone is cleared a bit slower, it could linger longer and feel a little stronger, meaning more drowsiness, dizziness, constipation, or slowed breathing in heavy doses.
Honestly, this is a theoretical concern based on lab and early research, not real-world reports, so I don't want to alarm you. Still, since hydrocodone is an opioid and any added sedation matters, it's worth running this combo past your pharmacist or doctor before mixing them.
- 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
- 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
- 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
- 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.
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.
Phellodendron Also Interacts With Other Medications
Phellodendron has 1,159 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Phellodendron
We haven’t checked that one against Phellodendron yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Phellodendron. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Phellodendron only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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 Ephedra (major).
By severity: 17 major · 276 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page
“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page
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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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:
Where Phellodendron and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
#307 of 1,452 supplements looked up here in the last 7 days
#450 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 Phellodendron
What is 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.
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.
No drugs match “”.
1,159 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Diphenhydramine ›
- Aspirin ›
- Hydrocortisone ›
- Insulin (rdna) ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Lidocaine ›
- Guaifenesin ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Insulin (pork) ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Insulin (human) ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
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.
- Levothyroxine ›
- Methylphenidate ›
- Ivermectin ›
- Rosuvastatin ›
- Escitalopram ›
- Acetaminophen ›
- Valacyclovir ›
- Docusate ›
- Hydroxyurea ›
- Sumatriptan ›
- Bupropion ›
- Acyclovir ›
- Amoxicillin ›
- Bendamustine ›
- Doxycycline ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Mitomycin ›
- Factor 7a ›
- Thyroid Hormone ›
- Cefaclor ›
- Carbidopa, Levodopa ›
- Ezetimibe ›
- Levodopa ›
- Vancomycin ›
- Phenylephrine ›
- Dirithromycin ›
- Lenvatinib ›
- Procainamide ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Bentoquatam ›
- Digoxin ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Succimer ›
- Tocainide ›
- Rocuronium ›
- Halothane ›
- Paracetamol ›
- Pizotifen ›
- Mitomycin C ›
- Gestodene ›
- Chenodiol ›
- Desflurane ›
Showing the 60 most looked-up of 1,670 medications checked with no known interaction — see the full Phellodendron 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
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine as a medicine that can lower these. This is not an interaction with Phellodendron — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
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 Phellodendron and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Phellodendron with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 3 interactions listed for Phellodendron and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Phellodendron and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.