Calamus + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 4 drug categories that Calamus can interact with; the most serious is rated moderate. Theoretically, concurrent use of CNS depressants and calamus might have an additive effect and increase the risk of sedative effects.
Read the full interaction reportCalamus and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Calamus interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 4 of those categories, so it can interact with Calamus in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 4Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CNS DEPRESSANTS — the group Calamus interacts with.
Animal research shows that calamus is a CNS depressant and increases gamma-aminobutyric acid levels.
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, includes two ingredients that already make people drowsy: hydrocodone (an opioid pain reliever) and chlorpheniramine (a sedating antihistamine). Calamus has shown calming, sedative-like activity in animal studies, partly by raising a brain chemical called GABA. Putting these together could pile on the drowsiness.
So in plain terms, you might feel more sleepy, foggy, or dizzy than usual, and in larger amounts that could mean slower, shallower breathing from the opioid. Keep in mind this concern is theoretical, based on lab and animal work rather than human studies. Calamus also has its own safety worries, so before mixing them, please check with your pharmacist or doctor.
- Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
- Koo, B. S., Park, K. S., Ha, J. H., Park, J. H., Lim, J. C., and Lee, D. U. Inhibitory effects of the fragrance inhalation of essential oil from Acorus gramineus on central nervous system. Biol Pharm.Bull. 2003;26(7):978-982. PubMed
- Panchal, G. M., Venkatakrishna-Bhatt, H., Doctor, R. B., and Vajpayee, S. Pharmacology of Acorus calamus L. Indian J Exp.Biol 1989;27(6):561-567.
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 4Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
In vitro research shows that calamus extract inhibits CYP2D6 enzyme.
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) is a bit tricky because the hydrocodone in it actually relies on a liver enzyme called CYP2D6 to turn into its more active pain-relieving form. Calamus has shown in lab-dish studies only that it can block CYP2D6. If that happened in your body, hydrocodone might convert less, meaning you could get less pain relief than expected. For the other ingredients like chlorpheniramine, blocking this enzyme could let them build up slightly, possibly adding to drowsiness or dry mouth.
Honestly, this is theoretical and based only on test-tube data, so I wouldn't lose sleep over it. The bigger concern is that calamus contains beta-asarone, which the FDA banned from foods. I'd skip the calamus and chat with your pharmacist if you're considering it.
- Pandit S, Mukherjee PK, Ponnusankar S, Venkatesh M, Srikanth N. Metabolism mediated interaction of a-asarone and Acorus calamus with CYP3A4 and CYP2D6. Fitoterapia 2011;82(3):369-74.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 4Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that calamus extract inhibits CYP3A4 enzyme.
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, an opioid pain reliever that your liver's CYP3A4 enzyme helps process. In test-tube studies, calamus appears to slow down that same enzyme. The worry is that if CYP3A4 is blocked, hydrocodone could build up a bit more than expected, which might mean more drowsiness, dizziness, constipation, or slowed breathing. That breathing concern is the one I'd watch most closely with any opioid.
I'll be honest with you: this is only a theoretical concern based on lab data, not real people, so it's hard to say how much it actually matters. Still, given calamus's own safety problems (it's banned from foods in the U.S.), I'd skip it and check with your pharmacist or doctor first.
- Pandit S, Mukherjee PK, Ponnusankar S, Venkatesh M, Srikanth N. Metabolism mediated interaction of a-asarone and Acorus calamus with CYP3A4 and CYP2D6. Fitoterapia 2011;82(3):369-74.
ANTICHOLINERGIC DRUGS
4 of 4Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under ANTICHOLINERGIC DRUGS.
In vitro evidence shows that calamus can inhibit acetylcholinesterase (AChE).
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 contains chlorpheniramine, an antihistamine with anticholinergic activity, meaning part of how it works is by blocking the chemical messenger acetylcholine. Calamus appears to do the opposite in lab studies, since it can block the enzyme that breaks down acetylcholine, leaving more of it around. In theory, that could push back against chlorpheniramine and make it a bit less effective, so things like a runny nose or sneezing might not be controlled as well.
I'll be honest with you though: this is based only on test-tube research, not real people, so we don't truly know if it matters in everyday use. Calamus also carries its own safety concerns and is best avoided regardless. If you're considering it, please run it by your pharmacist or doctor first.
- Oh, M. H., Houghton, P. J., Whang, W. K., and Cho, J. H. Screening of Korean herbal medicines used to improve cognitive function for anti-cholinesterase activity. Phytomedicine 2004;11(6):544-548. 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.
Calamus Also Interacts With Other Medications
Calamus has 1,097 moderate, 19 minor 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 Calamus
We haven’t checked that one against Calamus yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Calamus. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Calamus 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 Calamus as Part of a Dietary Supplement Product? Check It for Interactions
We hold 71 real supplement products containing Calamus, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Calamus. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Calamus — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Calamus 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.
#807 of 1,452 supplements looked up here in the last 7 days
#724 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 Calamus
What is Calamus?
- Digestive upset and gas
- Loss of appetite
- Memory and focus (traditional)
- Coughs and colds
- Calming or sedative effect (traditional)
Calamus is a swamp plant with a long history in Ayurvedic and traditional Chinese medicine, mostly for digestive and nervous-system complaints. However, it contains beta-asarone, a compound linked to cancer and other toxic effects in animal studies, which is why the U.S. FDA banned it from foods. Because of these safety concerns and a lack of solid human evidence, it is generally best avoided.
Other Drugs & Calamus
Browse every other medication we’ve checked against Calamus — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,097 interactions
- Diltiazem ›
- Nifedipine ›
- Diphenhydramine ›
- Hydrocortisone ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glycopyrrolate ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Ipratropium ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Procainamide ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Dimenhydrinate ›
- Everolimus ›
- Ivabradine ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meprobamate ›
- Nortriptyline ›
- Oxymorphone ›
- Pilocarpine ›
- Procyclidine ›
- Propoxyphene ›
- Rifampin ›
- Selegiline ›
Showing 60 of 1,097 moderate interactions — see all 1,097 on the Calamus page.
19 interactions
- Ranitidine ›
- Calcium Carbonate ›
- Famotidine ›
- Aluminum Hydroxide ›
- Cimetidine ›
- Nizatidine ›
- Dihydroxyaluminum Sodium Carbonate ›
- Magaldrate ›
- Ranitidine Bismuth Citrate ›
- Sodium Bicarbonate (otc Drug) ›
- Aluminum Hydroxide, Magnesium Hydroxide (otc Drug) ›
- Alginic Acid, Aluminum Hydroxide ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Aluminum Hydroxide, Magnesium Hydroxide, Simethicone (otc Drug) ›
- Aluminum, Magnesium (otc Drug) ›
- Aspirin, Calcium Carbonate, Magnesium Carbonate, Magnesium Oxide ›
- Aspirin, Citric Acid, Sodium Bicarbonate ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Famotidine, Ibuprofen ›
No interaction 1,713 drugs checked — show the list
We also checked Calamus against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Ivermectin ›
- Aspirin ›
- Rosuvastatin ›
- Acetaminophen ›
- Escitalopram ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Ibuprofen ›
- Tirzepatide ›
- Semaglutide ›
- Sumatriptan ›
- Metformin ›
- Amoxicillin ›
- Bupropion ›
- Bendamustine ›
- Acyclovir ›
- Methotrexate ›
- Doxycycline ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Naproxen ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cephalexin ›
- Cyclopentolate ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Ezetimibe ›
- Daptomycin ›
- Levothyroxine Sodium ›
- Dexmethylphenidate ›
- Mitomycin ›
- Amoxicillin, Clavulanate Potassium ›
- Hexobarbitone ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Acetaminophen, Ibuprofen ›
- Factor 7a ›
- Acetaminophen, Aspirin ›
- Levodopa ›
- Hethylphenidate Hcl ›
- Lenvatinib ›
- Cefaclor ›
- Azelaic Acid ›
- Phenylephrine ›
- Ibuprofen, Acetaminophen ›
- Hydroxychloroquine ›
- Tenecteplase ›
- Dirithromycin ›
- Vancomycin ›
- Pizotifen ›
- Triptorelin ›
- Bentoquatam ›
- Digoxin ›
- Acetylsalicylic Acid ›
- Ribavirin Aerosol ›
Showing the 60 most looked-up of 1,713 medications checked with no known interaction — see the full Calamus 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 Calamus — 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 Calamus and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Calamus with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 4 interactions listed for Calamus and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Calamus 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.