Drug & supplement interaction

Calamus + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

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

Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine

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. Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine

Amitriptyline, Perphenazine 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

Triavil combines amitriptyline (an older antidepressant) with perphenazine (an antipsychotic), and both already tend to make people drowsy and mentally foggy. Calamus, in animal studies, behaves like a calming agent on the nervous system, partly by raising a chemical called GABA. So the worry here is simple addition: stacking calamus on top of a medication that already sedates you could leave you more groggy than expected.

In real life that might look like extra sleepiness, trouble concentrating, dizziness when you stand, or feeling unsteady on your feet. Keep in mind this is theoretical, based on lab and animal work, not human studies. Separately, calamus has its own safety concerns and is best avoided. Please check with your pharmacist or doctor before combining 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

Amitriptyline, Perphenazine 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

Triavil combines amitriptyline (an antidepressant) with perphenazine (an antipsychotic), and both rely partly on the liver enzyme CYP2D6 to be cleared from your body. Lab studies suggest calamus may block that enzyme. If it does, these medicines could build up and hit harder than expected, raising the chance of side effects like drowsiness, dry mouth, constipation, blurred vision, dizziness on standing, a faster heartbeat, or stiff, restless movements.

Here's the honest part: this concern comes only from test-tube research, not from people, so it's theoretical for now. Still, calamus also carries its own safety worries (the FDA banned it from food), so I'd avoid it. Please run any calamus use by your pharmacist or doctor first.

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

Amitriptyline, Perphenazine 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

Triavil combines two active medicines, amitriptyline (an older antidepressant) and perphenazine (an antipsychotic). Your body relies partly on a liver enzyme called CYP3A4 to clear these. In lab dish studies, calamus appears to slow that enzyme down. If that holds true in people, it could let the medication build up a bit higher than expected.

What might that look like in real life? More of this combo's typical side effects, things like heavy drowsiness, dry mouth, constipation, blurred vision, dizziness when standing, and a faster heartbeat. I'll be honest with you though: this is only a theoretical concern based on test-tube work, not on real patients, so it's far from proven. Given calamus also carries its own safety red flags, I'd run it by your pharmacist or doctor before combining them.

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

Amitriptyline, Perphenazine 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

Triavil combines two medicines that both have anticholinergic activity, meaning they dampen the chemical messenger acetylcholine. Calamus appears to work in the opposite direction. In lab dish studies it blocks the enzyme that breaks down acetylcholine, so more of that messenger sticks around. In theory, that could push against what amitriptyline and perphenazine are doing and make them a little less effective.

I want to be honest about the evidence here: this is based only on test-tube work, not real people, so it is more of a maybe than a sure thing. Just as important, calamus contains beta-asarone, which has its own serious safety concerns and is best avoided. Please talk with your pharmacist or doctor before mixing the two rather than changing anything on your own.

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 Amitriptyline, Perphenazine 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. Amitriptyline, Perphenazine)
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 Amitriptyline, Perphenazine

This page covers Calamus only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,105 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 Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine Together: Common Questions

Can you take Calamus with Amitriptyline, Perphenazine?
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 Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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

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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.