Drug & supplement interaction

Pennyroyal + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.

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

Pennyroyal has a moderate interaction with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine. Concomitant use of pennyroyal essential oil and acetaminophen might increase the risk of acetaminophen-induced hepatotoxicity.

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

Pennyroyal and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ACETAMINOPHEN (Tylenol, others)

Concomitant use of pennyroyal essential oil and acetaminophen might increase the risk of acetaminophen-induced hepatotoxicity.
Pennyroyal is hepatotoxic and depletes hepatic glutathione levels in a similar manner to acetaminophen. A case report describes hepatic failure in a female who took pennyroyal and acetaminophen concurrently.
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

The piece of Colrex I want to focus on here is the acetaminophen (the same pain and fever reducer found in Tylenol). Your liver normally cleans up acetaminophen safely using a protective molecule called glutathione. The trouble is that pennyroyal oil leans on that exact same system and burns through your glutathione stores too. When both hit the liver at once, there is less protection to go around, and that raises the risk of liver damage, with warning signs like nausea, vomiting, belly pain on the right side, dark urine, or yellowing of the eyes or skin.

This is based on a single case report, so the evidence is thin, but pennyroyal oil is genuinely toxic and has caused deaths on its own. I would not swallow it at all. Please talk with your pharmacist or doctor before mixing anything like this.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bakerink JA, Gospe SM Jr, Dimand RJ, Eldridge MW. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 1996;98:944-7. DOI
  2. Sudekum M, Poppenga RH, Raju N, Braselton WE Jr. Pennyroyal oil toxicosis in a dog. J Am Vet Med Assoc 1992;200:817-8.. DOI
  3. Anderson IB, Mullen WH, Meeker JE, et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 1996;124:726-34. PubMed
  4. Fozard J, Hieger M. Hepatic failure from pennyroyal tea interaction with medications metabolized by the cytochrome P450 enzymes. Am J Ther 2019 Aug 13. doi: 10.1097/MJT.0000000000001052. [Epub ahead of print]. 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

Pennyroyal Also Interacts With Other Medications

Pennyroyal has 68 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine one above is one of them. If you take anything else, check it against the full list below.

Moderate 68 No known interaction 2,762 (incl. Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Pennyroyal

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

This page covers Pennyroyal only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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 Ephedra (major).

By severity: 18 major · 275 moderate · 45 minor.

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

“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction page

One more smart check

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

We hold 11 real supplement products containing Pennyroyal, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Pennyroyal. Your product may carry other ingredients that interact with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine too, on top of Pennyroyal — 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 Pennyroyal and Acetaminophen, Chlorpheniramine, Codeine, 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 Pennyroyal
Steady interest

#1,120 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Top 10%

#279 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 Pennyroyal

What is Pennyroyal?

  • Digestive upset
  • Menstrual cramps
  • Inducing menstruation or abortion (dangerous)
  • Colds and coughs
  • Insect repellent

Pennyroyal is a mint-family plant whose essential oil is highly toxic and has caused serious poisonings and deaths, especially when used to try to bring on a period or end a pregnancy. There is no reliable evidence that it safely treats any condition, and the oil should never be swallowed. Avoid pennyroyal and talk to your pharmacist or doctor about safer options.

Read the full Pennyroyal monograph & all interactions
Keep checking

Other Drugs & Pennyroyal

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

0Major
68Moderate
0Minor
2,761No known interaction
68 Moderate 2,761 No interaction
Moderate

68 interactions

Showing 60 of 68 moderate interactions — see all 68 on the Pennyroyal page.

No interaction 2,761 drugs checked — show the list

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

Showing the 60 most looked-up of 2,761 medications checked with no known interaction — see the full Pennyroyal list.

See the full Pennyroyal interactions page
See every supplement checked against Acetaminophen, Chlorpheniramine, Codeine, 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
Pennyroyal monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Codeine, 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 Pennyroyal and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions

Can you take Pennyroyal with Acetaminophen, Chlorpheniramine, Codeine, 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.
How serious is the Pennyroyal and Acetaminophen, Chlorpheniramine, Codeine, 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, Codeine, Phenylephrine and Pennyroyal?

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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.