Drug & supplement interaction

Calamus + Chlorpheniramine, Hydrocodone, Pseudoephedrine

Chlorpheniramine, Hydrocodone, Pseudoephedrine brand name: Tussend.

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

Chlorpheniramine, Hydrocodone, Pseudoephedrine 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 report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Calamus and Chlorpheniramine, Hydrocodone, Pseudoephedrine

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. Chlorpheniramine, Hydrocodone, Pseudoephedrine 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).

Moderate

CNS DEPRESSANTS

1 of 4

Why this applies to Chlorpheniramine, Hydrocodone, Pseudoephedrine

Chlorpheniramine, Hydrocodone, Pseudoephedrine falls under CNS DEPRESSANTS — the group Calamus interacts with.

Theoretically, concurrent use of CNS depressants and calamus might have an additive effect and increase the risk of sedative effects.
Animal research shows that calamus is a CNS depressant and increases gamma-aminobutyric acid levels.
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: this combination product already has two ingredients that can make you drowsy, chlorpheniramine (an antihistamine) and hydrocodone (an opioid cough/pain ingredient). Calamus, at least in animal studies, seems to act as a mild nervous-system depressant by nudging up a calming brain chemical called GABA. Stack them together and you may feel more sleepy than expected, with foggy thinking, dizziness, slowed breathing, or trouble staying alert to drive.

I'll be honest with you, this is a theoretical concern based on lab and animal work, not solid human proof. Still, since the hydrocodone piece already carries real sedation risk, I'd lean cautious. Calamus also has its own safety baggage, so please check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. 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
  3. 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.
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 4

Chlorpheniramine, Hydrocodone, Pseudoephedrine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, taking calamus with drugs metabolized by CYP2D6 might increase drug levels and potentially increase the risk of adverse effects.
In vitro research shows that calamus extract inhibits CYP2D6 enzyme.
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 this combination product. One of its ingredients, hydrocodone, is actually a prodrug. Your liver uses an enzyme called CYP2D6 to convert it into hydromorphone, which gives a good chunk of its pain-relieving punch. Lab studies (in test tubes only, not in people) suggest calamus may block that same enzyme. If that held true in your body, hydrocodone might be converted less efficiently, so you could get weaker pain relief than expected.

The flip side is that the parent hydrocodone could linger longer, possibly adding to drowsiness or constipation. Honestly, this is theoretical and based only on lab work, so I wouldn't panic. Given calamus has its own safety concerns, it's worth running past your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

Chlorpheniramine, Hydrocodone, Pseudoephedrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, taking calamus with drugs metabolized by CYP3A4 might increase drug levels and potentially increase the risk of adverse effects.
In vitro research shows that calamus extract inhibits CYP3A4 enzyme.
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 this combo cough-and-cold product (which pairs the opioid hydrocodone with an antihistamine and a decongestant): lab studies hint that calamus may slow down a liver enzyme called CYP3A4, and that enzyme helps process hydrocodone. In theory, if calamus blocks it, more of the medicine could linger in your body. That could mean stronger effects like extra drowsiness, dizziness, constipation, or slowed breathing, which is the part that worries me most with any opioid.

I want to be honest, though: this is only a test-tube finding, not something proven in people, so the real-world risk is uncertain. On top of that, calamus has its own safety concerns and is best avoided. Please run this by your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.
Moderate

ANTICHOLINERGIC DRUGS

4 of 4

Chlorpheniramine, Hydrocodone, Pseudoephedrine also falls under ANTICHOLINERGIC DRUGS.

Theoretically, concurrent use of anticholinergic drugs and calamus might decrease the effectiveness of the anticholinergic drug.
In vitro evidence shows that calamus can inhibit acetylcholinesterase (AChE).
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 has three parts, but the piece that matters here is chlorpheniramine, the antihistamine. It works partly by blocking acetylcholine activity (it has anticholinergic effects). In lab dishes, calamus appears to do the opposite, boosting acetylcholine by slowing the enzyme that breaks it down. So in theory, calamus could work against chlorpheniramine and make it a little less effective at drying up a runny nose or calming a cough.

I want to be honest about the strength of this: it comes from test-tube research only, not real people, so it may not amount to much in practice. The bigger concern is that calamus contains beta-asarone, which the FDA banned from foods over safety worries, so I'd steer clear of it regardless. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.

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

Calamus Also Interacts With Other Medications

Calamus has 1,097 moderate, 19 minor known drug interactions in our database — the Chlorpheniramine, Hydrocodone, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Moderate 1,097 Minor 19 No known interaction 1,714 (incl. Chlorpheniramine, Hydrocodone, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Calamus

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

Everything else you take

See Every Supplement That Interacts With Chlorpheniramine, Hydrocodone, Pseudoephedrine

This page covers Calamus only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Chlorpheniramine, Hydrocodone, Pseudoephedrine page lists 285 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), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 16 major · 228 moderate · 41 minor.

From our pharmacist’s overview on the Chlorpheniramine, Hydrocodone, Pseudoephedrine page

“Tussend combines three drugs in one cough medicine, the opioid hydrocodone, the antihistamine chlorpheniramine, and the decongestant pseudoephedrine, so supplements can collide with it from several directions. I treat its list of 285 interacting ingredients as one that deserves real respect, and the 16 rated major are what to understan…”

Reviewed by 2 · Jul 18, 2026

Open the Chlorpheniramine, Hydrocodone, Pseudoephedrine interaction page

One more smart check

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 Chlorpheniramine, Hydrocodone, Pseudoephedrine 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:

How much people look this up

Where Calamus and Chlorpheniramine, Hydrocodone, Pseudoephedrine 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 Calamus
Steady interest

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

29 days ago today
Medication Chlorpheniramine, Hydrocodone, Pseudoephedrine
Steady interest

#2,217 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 Calamus

What is Calamus?

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.

Read the full Calamus monograph & all interactions
Keep checking

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.

0Major
1,097Moderate
19Minor
1,713No known interaction
1,097 Moderate 19 Minor 1,713 No interaction
Moderate

1,097 interactions

Showing 60 of 1,097 moderate interactions — see all 1,097 on the Calamus page.

Minor

19 interactions

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.

Showing the 60 most looked-up of 1,713 medications checked with no known interaction — see the full Calamus list.

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

Can you take Calamus with Chlorpheniramine, Hydrocodone, Pseudoephedrine?
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 Calamus and Chlorpheniramine, Hydrocodone, Pseudoephedrine?
Chlorpheniramine, Hydrocodone, Pseudoephedrine belongs to more than one drug category, and Calamus 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 Calamus and Chlorpheniramine, Hydrocodone, Pseudoephedrine 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine and Calamus?

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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.