Drug & supplement interaction

Calamus + Memantine, Donepezil

Memantine, Donepezil brand name: Namzaric.

Moderate Interaction
The bottom line Moderate

Memantine, Donepezil falls into 3 drug categories that Calamus can interact with; the most serious is rated moderate. Theoretically, taking calamus with drugs metabolized by CYP2D6 might increase drug levels and potentially increase the risk of adverse effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Calamus and Memantine, Donepezil

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Calamus interacts with whole categories of medication. Memantine, Donepezil falls into 3 of those categories, so it can interact with Calamus in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Memantine, Donepezil

Memantine, Donepezil falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Calamus interacts with.

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

Namzaric combines two Alzheimer's medicines: memantine and donepezil. The donepezil part leans on a liver enzyme called CYP2D6 to be cleared from your body. In test-tube studies, calamus appears to slow that enzyme down. If that happened in real life, donepezil could build up a bit more than usual, which might mean more of its typical side effects like nausea, diarrhea, loss of appetite, a slow heartbeat, dizziness, or trouble sleeping. Neither of these drugs is a prodrug, so this points toward stronger effects, not weaker ones.

The good news: this is only a theoretical concern based on lab research, not human studies. Still, calamus carries its own safety worries, so I'd skip it and check with your doctor or pharmacist before adding any supplement.

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

2 of 3

Memantine, Donepezil 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 Namzaric (the memantine plus donepezil combo). The donepezil part is cleared in part by a liver enzyme called CYP3A4. In lab studies (not human studies), calamus appears to slow that enzyme down. If that happened in your body, donepezil could build up a bit more than expected, which might mean more of its usual side effects: nausea, diarrhea, stomach cramps, dizziness, a slower heart rate, or trouble sleeping.

I want to be honest though: this is theoretical, based only on test-tube work, so the real-world risk is uncertain. Calamus has its own safety problems and is best avoided anyway. Please don't change your Namzaric, but do run any calamus use past your pharmacist or doctor first.

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

CHOLINERGIC DRUGS

3 of 3

Memantine, Donepezil also falls under CHOLINERGIC DRUGS.

Theoretically, concurrent use of cholinergic drugs and calamus might have an additive effect and increase the risk of cholinergic effects.
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

Namzaric combines two medicines, and the donepezil part works by blocking an enzyme called acetylcholinesterase. That lets more acetylcholine, a key brain messenger, stick around. Here's the thing: lab studies suggest calamus may block that same enzyme. So in theory, pairing them could pile on too much of that cholinergic activity.

What might that look like? Think nausea, diarrhea, stomach cramps, drooling, a slow heartbeat, dizziness, or muscle issues. I'll be honest though, this concern comes only from test-tube and animal research, not real people, so it's more of a caution than a proven problem. On top of that, calamus contains beta-asarone and is best avoided anyway. Please check with your pharmacist or doctor before combining them.

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 Memantine, Donepezil one above is among them. If you take anything else, check it against the full list below.

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 Memantine, Donepezil

This page covers Calamus only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Memantine, Donepezil page lists 172 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Threonine (major) and 1,3-dmaa (moderate).

By severity: 4 major · 126 moderate · 42 minor.

Open the Memantine, Donepezil 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 Memantine, Donepezil 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 Memantine, Donepezil 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
Top half

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

29 days ago today
Medication Memantine, Donepezil
Top 25%

#421 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
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
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

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Pharmacist Counseling Corner

Taking Calamus and Memantine, Donepezil Together: Common Questions

Can you take Calamus with Memantine, Donepezil?
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 3 interactions listed for Calamus and Memantine, Donepezil?
Memantine, Donepezil 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 Memantine, Donepezil 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.