Oregon Grape + 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 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 reportOregon Grape and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
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. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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).
CNS DEPRESSANTS
1 of 3Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CNS DEPRESSANTS — the group Oregon Grape interacts with.
Animal research suggests that berberine, a constituent of Oregon grape, can have sedative 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, sold as Hycomine Compound, already has two ingredients that can make you drowsy: hydrocodone (an opioid pain reliever and cough suppressant) and chlorpheniramine (a sedating antihistamine). The concern here is simple. Berberine, a compound in Oregon grape, showed sedative effects in animal studies, so in theory it could add to that sleepiness.
If they stacked up, you might feel extra drowsy, foggy, dizzy, or slow to react, which matters before driving or operating machinery. I'll be honest though, this is only a theoretical worry based on animal data, not human cases, so it's not something to panic over. Still, if you plan to use both, run it by your pharmacist or doctor first.
- 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.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (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.
This combination product (Hycomine Compound) contains hydrocodone, which is the piece that matters here. Hydrocodone is a prodrug that your liver partly converts through the CYP2D6 enzyme into hydromorphone, a stronger painkiller. The berberine in Oregon grape can gently slow down that same CYP2D6 enzyme.
Because of that, in theory you might convert a little less hydrocodone into its more potent form, which could mean slightly less pain relief for some people. The evidence is mostly lab-based and fairly limited, so this is more of a theoretical concern than a sure thing. Still, if your pain control changes after starting Oregon grape, or you notice extra grogginess, dizziness, or constipation, please check in with your pharmacist or doctor before changing anything.
- 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.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (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 product (Hycomine Compound) contains several ingredients, and the one that matters most here is hydrocodone, the opioid pain reliever. Hydrocodone is partly broken down by a liver enzyme called CYP3A4. The berberine in Oregon grape can mildly slow that same enzyme down. In theory, that could let a bit more hydrocodone build up in your system, which may mean stronger effects like extra drowsiness, dizziness, constipation, or slowed breathing.
Honestly though, this concern is theoretical, based mostly on lab work rather than real patients, so I wouldn't lose sleep over it. Still, since this medicine already makes you sleepy, it's worth a quick chat with your pharmacist or doctor before adding an Oregon grape supplement, especially concentrated capsules.
- 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.
Oregon Grape Also Interacts With Other Medications
Oregon Grape has 1,217 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 Oregon Grape
We haven’t checked that one against Oregon Grape yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Oregon Grape. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Oregon Grape 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 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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:
Where Oregon Grape 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.
#271 of 1,452 supplements looked up here in the last 7 days
#443 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 Oregon Grape
What is 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.
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.
No drugs match “”.
1,217 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Diphenhydramine ›
- Aspirin ›
- Hydrocortisone ›
- Insulin (rdna) ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Insulin (pork) ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Insulin (human) ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Amphetamine ›
- Buprenorphine ›
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.
- Levothyroxine ›
- Methylphenidate ›
- Rosuvastatin ›
- Escitalopram ›
- Acetaminophen ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Bupropion ›
- Amoxicillin ›
- Acyclovir ›
- Bendamustine ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Levothyroxine Sodium ›
- Dexmethylphenidate ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Lenvatinib ›
- Phenylephrine ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Amoxicillin, Clavulanate Potassium ›
- Procainamide ›
- Hydroxychloroquine ›
- Azelaic Acid ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Tocainide ›
- Pizotifen ›
- Rocuronium ›
- Succimer ›
- Mitomycin C ›
- Paracetamol ›
- Halothane ›
- Desflurane ›
- Chenodiol ›
- Gestodene ›
- Niacin (prescription Drug) ›
- Metronidazole ›
- Cabergoline ›
Showing the 60 most looked-up of 1,612 medications checked with no known interaction — see the full Oregon Grape 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 Oregon Grape — 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 Oregon Grape and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Oregon Grape with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 3 interactions listed for Oregon Grape and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Oregon Grape and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Oregon Grape?
Our pharmacists answer your medication & supplement questions — free.
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.