Drug & supplement interaction

Ceylon Leadwort + Acetaminophen, Codeine, Doxylamine

Acetaminophen, Codeine, Doxylamine brand name: Mersyndol.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Codeine, Doxylamine falls into 3 drug categories that Ceylon Leadwort can interact with; the most serious is rated moderate. Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 2D6 (CYP2D6) in vitro.

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

Ceylon Leadwort and Acetaminophen, Codeine, Doxylamine

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

Why Are There 3 Interactions?

Ceylon Leadwort interacts with whole categories of medication. Acetaminophen, Codeine, Doxylamine falls into 3 of those categories, so it can interact with Ceylon Leadwort 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 Acetaminophen, Codeine, Doxylamine

Acetaminophen, Codeine, Doxylamine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Ceylon Leadwort interacts with.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 2D6 (CYP2D6) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP2D6. Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), fluoxetine (Prozac), ondansetron (Zofran), tramadol (Ultram), and others.
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 Mersyndol: the codeine part is a prodrug. Your body has to convert it using an enzyme called CYP2D6 to turn it into morphine, which is what actually relieves pain. Ceylon Leadwort contains plumbagin, which (in lab studies only) seems to block that same enzyme. If it blocks CYP2D6, you'd convert less codeine into morphine, so you might get weaker pain relief rather than more.

I want to be honest about the strength here: this is purely test-tube and animal data, never confirmed in real people, so it's theoretical. Still, since this combo also has sedating doxylamine on board, it's worth running by your pharmacist or doctor before mixing the two.

References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Acetaminophen, Codeine, Doxylamine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 1A2 (CYP1A2) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP1A2. Some substrates of CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), zileuton (Zyflo), zolmitriptan (Zomig), and others.
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 honest picture with Mersyndol (which combines acetaminophen, codeine, and the sedating antihistamine doxylamine). In lab tests, the plumbagin in Ceylon Leadwort blocked an enzyme called CYP1A2. This enzyme isn't the main one that handles these three ingredients (codeine relies mostly on CYP2D6 and CYP3A4, and acetaminophen is cleared by other routes), so the overlap here is loose at best.

Even so, the only evidence is from test tubes and animals, not people. No real-world cases have been reported. If levels did nudge up at all, you might notice more drowsiness, dizziness, constipation, or nausea. That's worth knowing since this combo already makes many folks sleepy. Concentrated supplement doses matter more than tiny amounts. Please run it by your pharmacist or doctor before combining them.

References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Codeine, Doxylamine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 2E1 (CYP2E1) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP2E1. Some drugs metabolized by CYP2E1 include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and anesthetics such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), methoxyflurane (Penthrane).
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 piece that matters for Mersyndol: it contains acetaminophen, and one of the ways your liver clears acetaminophen is through an enzyme called CYP2E1. In lab dishes, plumbagin (the active compound in Ceylon Leadwort) appears to slow that enzyme down. In theory, that could let a bit more acetaminophen linger in your system. Since acetaminophen in large amounts is hard on the liver, this is worth being thoughtful about.

I'll be honest with you though, this is test-tube evidence only, never reported in real people, so I wouldn't lose sleep over it. The bigger everyday concern is simply not taking extra acetaminophen from other products. If you'd like to use this herb, just run it by your pharmacist or doctor first.

References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. 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

Ceylon Leadwort Also Interacts With Other Medications

Ceylon Leadwort has 1,096 moderate known drug interactions in our database — the Acetaminophen, Codeine, Doxylamine 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 Ceylon Leadwort

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Codeine, Doxylamine

This page covers Ceylon Leadwort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Codeine, Doxylamine page lists 261 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 Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 208 moderate · 42 minor.

From our pharmacist’s overview on the Acetaminophen, Codeine, Doxylamine page

“Mersyndol pairs acetaminophen with codeine and doxylamine, two sedating drugs in one tablet, so I read its interaction list with genuine vigilance. Of the 261 supplements and herbs on file, the biggest hazard is anything else that slows the brain: 78 ingredients add sedation, and that group holds several of the 11 major-rated entries,…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Codeine, Doxylamine interaction page

One more smart check

Taking Ceylon Leadwort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 96 real supplement products containing Ceylon Leadwort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ceylon Leadwort. Your product may carry other ingredients that interact with Acetaminophen, Codeine, Doxylamine too, on top of Ceylon Leadwort — 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 Ceylon Leadwort and Acetaminophen, Codeine, Doxylamine 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 Ceylon Leadwort
Top half

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

29 days ago today
Medication Acetaminophen, Codeine, Doxylamine
Steady interest

#1,587 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 Ceylon Leadwort

What is Ceylon Leadwort?

  • Digestive complaints and poor appetite
  • Skin conditions and wounds (applied to the skin)
  • Joint pain and swelling
  • Traditional 'metabolism-boosting' tonics
  • Antimicrobial folk remedy

Ceylon Leadwort (Plumbago zeylanica) is a plant long used in Ayurvedic and other traditional medicine systems, mainly for digestion, skin problems, and pain. Solid human studies are lacking, and the plant contains plumbagin, a compound that can irritate skin and tissues and may be unsafe in larger amounts. Talk to a pharmacist or doctor before using it, and avoid it in pregnancy.

Read the full Ceylon Leadwort monograph & all interactions
Keep checking

Other Drugs & Ceylon Leadwort

Browse every other medication we’ve checked against Ceylon Leadwort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
1,096Moderate
0Minor
1,733No known interaction
Moderate

1,096 interactions

Showing 60 of 1,096 moderate interactions — see all 1,096 on the Ceylon Leadwort page.

No interaction 1,733 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 Ceylon Leadwort and Acetaminophen, Codeine, Doxylamine Together: Common Questions

Can you take Ceylon Leadwort with Acetaminophen, Codeine, Doxylamine?
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 Ceylon Leadwort and Acetaminophen, Codeine, Doxylamine?
Acetaminophen, Codeine, Doxylamine belongs to more than one drug category, and Ceylon Leadwort 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 Ceylon Leadwort and Acetaminophen, Codeine, Doxylamine 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.