Drug & supplement interaction

Rhubarb + Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine brand names: Protid, Histex SR, Alka-Seltzer PLUS.

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

Acetaminophen, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine

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, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine 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

This combo cold-and-allergy product pairs acetaminophen with chlorpheniramine and phenylephrine. The concern here is mostly about the acetaminophen piece. Rhubarb root, when taken as a concentrated supplement over a long stretch, contains anthraquinones that animal studies suggest may stress the kidneys. Pile that on top of medicines that can also be hard on the kidneys, and the theory is the two together could add up.

I want to be honest about the evidence: this is weak, based on animal data and a single case report involving a different drug. The rhubarb stalks in a pie won't do this. If you regularly take rhubarb supplements, just mention it to your pharmacist or doctor before pairing it with frequent acetaminophen use.

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 2

Acetaminophen, Chlorpheniramine, Phenylephrine 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 combo cold medicine includes acetaminophen (Tylenol), which your liver has to process. The concern here isn't about rhubarb changing how the drug works in your body. Instead, both rhubarb root supplements and acetaminophen can be hard on the liver on their own, so taking concentrated rhubarb alongside acetaminophen could, in theory, add to the strain.

I'll be honest: this worry comes mostly from animal studies and a small number of reported liver injury cases, so the evidence is thin. Eating rhubarb stalks in a pie is not the issue here. The bigger picture is simply not overdoing acetaminophen and being cautious with concentrated rhubarb root products. If you take this medicine regularly or have any liver concerns, check in with your pharmacist or doctor first.

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

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, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine)
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, Chlorpheniramine, Phenylephrine

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, Chlorpheniramine, Phenylephrine, 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, Chlorpheniramine, Phenylephrine

This page covers Rhubarb only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Phenylephrine page lists 292 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: 14 major · 232 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Phenylephrine page

“Picture the week you are sick enough to reach for Alka-Seltzer PLUS or another acetaminophen, chlorpheniramine, and phenylephrine combination, while still taking whatever supplements you always take. That is where trouble hides, and with 14 of its 292 supplement interactions rated major, this medicine warrants real vigilance.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine 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%

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

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Phenylephrine
Top 25%

#528 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, Chlorpheniramine, Phenylephrine, 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, Chlorpheniramine, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Phenylephrine, 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, Chlorpheniramine, Phenylephrine Together: Common Questions

Can you take Rhubarb with Acetaminophen, Chlorpheniramine, Phenylephrine?
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, Chlorpheniramine, Phenylephrine?
Acetaminophen, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine 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.