Drug & supplement interaction

Rhubarb + Acetaminophen, Codeine, Doxylamine

Acetaminophen, Codeine, Doxylamine brand name: Mersyndol.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Codeine, Doxylamine falls into 2 drug categories that Rhubarb can interact with; the most serious is rated moderate. Theoretically, long-term use of anthraquinones from rhubarb might increase the risk of nephrotoxicity when used with nephrotoxic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Rhubarb and Acetaminophen, Codeine, Doxylamine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Rhubarb interacts with whole categories of medication. Acetaminophen, Codeine, Doxylamine falls into 2 of those categories, so it can interact with Rhubarb in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

NEPHROTOXIC DRUGS

1 of 2

Why this applies to Acetaminophen, Codeine, Doxylamine

Acetaminophen, Codeine, Doxylamine falls under NEPHROTOXIC DRUGS — the group Rhubarb interacts with.

Theoretically, long-term use of anthraquinones from rhubarb might increase the risk of nephrotoxicity when used with nephrotoxic drugs.
The anthraquinone constituents of rhubarb have been shown to induce nephrotoxicity in animal research. Additionally, in a case report, a 23-year old female presented with kidney failure after taking 6 tablets of a proprietary slimming agent (found to contain the anthraquinones emodin and aloe-emodin from rhubarb) daily for 6 weeks and then adding diclofenac 25 mg 4 times daily for 2 days. The authors postulate that the anthraquinone constituents of rhubarb contributed to the renal dysfunction, and the addition of diclofenac, a nephrotoxic drug, led to renal failure. Until more is known, advise patients to avoid taking rhubarb if they are taking other potentially nephrotoxic drugs.
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: rhubarb root (the concentrated supplement kind, not a slice of rhubarb pie) contains compounds called anthraquinones. In animal studies, and in one case report, these have been linked to kidney stress, especially when paired with medicines that are already tough on the kidneys. The acetaminophen part of Mersyndol is one of those medicines, particularly with heavy or long-term use.

I want to be honest with you: this is mostly theoretical, based on lab and animal data plus a single case, so I'm not trying to scare you. But to play it safe, it's wise not to combine regular rhubarb root supplements with this product. Food amounts of rhubarb stalk are very unlikely to matter. Run it by your pharmacist or doctor before mixing the two.

References
  1. Kwan TH, Tong MK, Leung KT, et al. Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Hong Kong Med J 2006;12:394-7.
  2. Yan, M., Zhang, L. Y., Sun, L. X., Jiang, Z. Z., and Xiao, X. H. Nephrotoxicity study of total rhubarb anthraquinones on Sprague Dawley rats using DNA microarrays. J Ethnopharmacol. 4-15-2006; PubMed
Moderate

HEPATOTOXIC DRUGS

2 of 2

Acetaminophen, Codeine, Doxylamine also falls under HEPATOTOXIC DRUGS.

Theoretically, concomitant use of rhubarb with potentially hepatotoxic drugs might increase the risk of developing liver damage.
Some animal research suggests that anthraquinones in rhubarb might have hepatotoxic effects. Also, rhubarb use has been linked to at least 24 cases of liver injury, although details on the dose of rhubarb and duration of use in these cases is unclear.
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 Mersyndol, which combines acetaminophen, codeine, and doxylamine. The piece we're watching is the acetaminophen (Tylenol) component, since acetaminophen is already known to stress the liver when used in high doses or over long periods. Rhubarb root contains compounds called anthraquinones, and there's a theoretical concern that these could add a bit of extra strain on the liver.

I want to be honest about the evidence here. This worry comes from animal studies and a small number of unclear case reports, so it's not strongly proven. Eating rhubarb stalks in a pie isn't the same as taking concentrated root supplements. Still, if you regularly take rhubarb supplements alongside Mersyndol, mention it to your pharmacist or doctor so they can keep an eye on your liver health.

References
  1. Byeon JH, Kil JH, Ahn YC, Son CG. Systematic review of published data on herb induced liver injury. J Ethnopharmacol 2019;233:190-6. PubMed
  2. Zhao D, Feng SX, Zhang HJ, et al. Pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones in rats after oral administration of effective fraction of anthraquinones from rheum officinale. Xenobiotica. 2021;51(8):916-925. 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

Rhubarb Also Interacts With Other Medications

Rhubarb has 657 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 Rhubarb

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

From our Q&A

Questions About Rhubarb or Acetaminophen, Codeine, Doxylamine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Rhubarb or Acetaminophen, Codeine, Doxylamine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Codeine, Doxylamine

This page covers Rhubarb 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 Rhubarb as Part of a Dietary Supplement Product? Check It for Interactions

We hold 133 real supplement products containing Rhubarb, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Rhubarb. Your product may carry other ingredients that interact with Acetaminophen, Codeine, Doxylamine too, on top of Rhubarb — 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 Rhubarb 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 Rhubarb
Top 25%

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

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

#1,593 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 Rhubarb

What is Rhubarb?

Rhubarb
  • Constipation
  • Digestive upset
  • Menopausal symptoms
  • Kidney and liver conditions (traditional)
  • Pancreatitis (hospital/traditional use)

Rhubarb root has a long history of use as a laxative and in traditional Chinese medicine, and its edible stalks are a common food. Most medicinal claims are backed by limited or low-quality evidence, and the root can cause cramping and diarrhea. The leaves are toxic and should never be eaten, and rhubarb supplements are best avoided in pregnancy and breastfeeding.

Read the full Rhubarb monograph & all interactions
Keep checking

Other Drugs & Rhubarb

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

0Major
657Moderate
0Minor
2,172No known interaction
Moderate

657 interactions

Showing 60 of 657 moderate interactions — see all 657 on the Rhubarb page.

No interaction 2,172 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 Rhubarb and Acetaminophen, Codeine, Doxylamine Together: Common Questions

Can you take Rhubarb 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 2 interactions listed for Rhubarb and Acetaminophen, Codeine, Doxylamine?
Acetaminophen, Codeine, Doxylamine belongs to more than one drug category, and Rhubarb 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 Rhubarb 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.