Drug & supplement interaction

Rhubarb + Acetaminophen, Caffeine, Pyrilamine

Acetaminophen, Caffeine, Pyrilamine brand name: Midol Max Strength Menstrual.

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

Acetaminophen, Caffeine, Pyrilamine falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Rhubarb and Acetaminophen, Caffeine, Pyrilamine

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

Why Are There 3 Interactions?

Rhubarb interacts with whole categories of medication. Acetaminophen, Caffeine, Pyrilamine falls into 3 of those categories, so it can interact with Rhubarb in 3 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 3

Why this applies to Acetaminophen, Caffeine, Pyrilamine

Acetaminophen, Caffeine, Pyrilamine 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 with your Midol (acetaminophen, caffeine, and pyrilamine) and rhubarb root. The concern isn't about how rhubarb changes the drug levels in your body. Instead, certain compounds in rhubarb root called anthraquinones (like emodin and rhein) may be hard on the kidneys when taken long-term in concentrated supplement form. Acetaminophen in large or frequent doses can also stress the kidneys, so the worry is that the two together could add up.

I'll be honest, this is mostly theoretical, based on animal studies and a single case report involving a different drug. Occasional Midol for cramps with rhubarb in a pie won't be the issue. The caution is really for daily, high-dose rhubarb root supplements. If that's you, please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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 3

Acetaminophen, Caffeine, Pyrilamine 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

This Midol formula contains acetaminophen, which your liver has to process, and high or frequent doses can stress it. The concern here isn't that rhubarb changes how the drug is broken down. Instead, both rhubarb root and acetaminophen can each be hard on the liver, so using them together could, in theory, add up to a bit more strain.

I want to be honest about how soft this evidence is. It comes mostly from animal studies and a handful of poorly documented case reports, so it's theoretical, not proven. Eating rhubarb stalks in a pie is very different from taking concentrated root supplements long-term. Still, if you take rhubarb supplements regularly or drink alcohol often, mention it to your pharmacist or doctor before pairing it with acetaminophen.

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

DIURETIC DRUGS

3 of 3

Acetaminophen, Caffeine, Pyrilamine also falls under DIURETIC DRUGS.

Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia.
Rhubarb has stimulant laxative effects. Overuse of rhubarb might cause potassium depletion and compound diuretic-induced potassium loss.
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 thing about this combo: the worry isn't really with the active ingredients in Midol (acetaminophen for pain, caffeine, and pyrilamine, an antihistamine). The flagged concern comes from the caffeine, which acts as a mild diuretic, meaning it can make you lose a little extra fluid and potassium through your urine.

Rhubarb root taken as a laxative can also drain potassium when used heavily or often. Stack the two together and, in theory, your potassium could dip low enough to cause muscle cramps, weakness, or an irregular heartbeat. I want to stress this is theoretical and based on how these things work, not on solid studies, and occasional use or eating rhubarb stalks in food won't do this. If you regularly use rhubarb root supplements, just mention it to your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.

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

Moderate 657 No known interaction 2,173 (incl. Acetaminophen, Caffeine, Pyrilamine)
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, Caffeine, Pyrilamine

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, Caffeine, Pyrilamine, 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, Caffeine, Pyrilamine

This page covers Rhubarb only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Pyrilamine page lists 322 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Grapefruit (major).

By severity: 16 major · 260 moderate · 46 minor.

Open the Acetaminophen, Caffeine, Pyrilamine 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, Caffeine, Pyrilamine 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, Caffeine, Pyrilamine 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%

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

29 days ago today
Medication Acetaminophen, Caffeine, Pyrilamine
Top half

#1,064 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
657 Moderate 2,172 No 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

We also checked Rhubarb against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,172 medications checked with no known interaction — see the full Rhubarb list.

See the full Rhubarb interactions page
See every supplement checked against Acetaminophen, Caffeine, Pyrilamine, 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
Rhubarb monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Caffeine, Pyrilamine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Pyrilamine, 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 Rhubarb and Acetaminophen, Caffeine, Pyrilamine Together: Common Questions

Can you take Rhubarb with Acetaminophen, Caffeine, Pyrilamine?
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 Rhubarb and Acetaminophen, Caffeine, Pyrilamine?
Acetaminophen, Caffeine, Pyrilamine 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, Caffeine, Pyrilamine 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 Acetaminophen, Caffeine, Pyrilamine and Rhubarb?

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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.