Drug & supplement interaction

Cascara Sagrada + 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 2 drug categories that Cascara Sagrada can interact with; the most serious is rated moderate. Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with diuretic drugs.

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

Cascara Sagrada and Acetaminophen, Caffeine, Pyrilamine

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

Why Are There 2 Interactions?

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

Moderate

DIURETIC DRUGS

1 of 2

Why this applies to Acetaminophen, Caffeine, Pyrilamine

Acetaminophen, Caffeine, Pyrilamine falls under DIURETIC DRUGS — the group Cascara Sagrada interacts with.

Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with diuretic drugs.
Cascara sagrada has stimulant laxative effects, and long-term use has been associated with hypokalemia.
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 pairing cascara sagrada with a product like Midol Max Strength (which combines acetaminophen, caffeine, and pyrilamine). The medicine itself isn't really the issue. The concern lies with the caffeine piece, since caffeine has a mild water-pill (diuretic) effect, and cascara is a stimulant laxative. Both can nudge your body to lose potassium, especially if the laxative is used for more than a few days.

I want to be straight with you: this is a theoretical worry based on how these things work, not something proven to happen often. Still, low potassium can leave you feeling weak, crampy, or with an irregular heartbeat. Cascara is best used only briefly, if at all. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Caffeine, Pyrilamine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, cascara sagrada might decrease the effects of CYP3A4 substrates.
In vitro research suggests that cascara sagrada can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.
Severity Minor 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

If you reach for a Midol Max Strength tablet (acetaminophen, caffeine, and pyrilamine) while taking cascara sagrada, here's the honest picture: the only signal we have comes from lab dish studies, not from people. Those studies hint that cascara might gently speed up a liver enzyme called CYP3A4, and far more weakly than a strong known inducer. In theory, faster clearance could trim how well these ingredients work, so you might notice slightly less relief from the caffeine pick-me-up or the antihistamine.

Realistically, this is very unlikely to cause you trouble. The evidence is weak, the effect is small, and occasional short-term use of either product is what matters most. If you plan to use cascara regularly, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mazzari ALDA, Lacerda MG, Milton FA, et al. In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity. Front Pharmacol 2022;13:826395. 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

Cascara Sagrada Also Interacts With Other Medications

Cascara Sagrada has 121 moderate, 623 minor 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 121 Minor 623 No known interaction 2,086 (incl. Acetaminophen, Caffeine, Pyrilamine)
Taking anything else?

Check Another of Your Medications Against Cascara Sagrada

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Pyrilamine

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

We hold 849 real supplement products containing Cascara Sagrada, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cascara Sagrada. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Pyrilamine too, on top of Cascara Sagrada — 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 Cascara Sagrada 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 Cascara Sagrada
Top 25%

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

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

#806 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 Cascara Sagrada

What is Cascara Sagrada?

Cascara Sagrada
  • Constipation
  • Bowel cleansing before procedures
  • Hemorrhoids
  • Traditional liver and gallbladder remedy

Cascara sagrada is a stimulant laxative made from the aged bark of a Pacific Northwest tree, used mainly for short-term relief of constipation. Because it can cause cramping, dehydration, and electrolyte problems—and was removed from over-the-counter laxative products in the U.S. due to safety concerns—it should only be used briefly, if at all, and with guidance from a pharmacist or doctor.

Read the full Cascara Sagrada monograph & all interactions
Keep checking

Other Drugs & Cascara Sagrada

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

0Major
121Moderate
623Minor
2,085No known interaction
121 Moderate 623 Minor 2,085 No interaction
Moderate

121 interactions

Showing 60 of 121 moderate interactions — see all 121 on the Cascara Sagrada page.

Minor

623 interactions

Showing 60 of 623 minor interactions — see all 623 on the Cascara Sagrada page.

No interaction 2,085 drugs checked — show the list

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

Showing the 60 most looked-up of 2,085 medications checked with no known interaction — see the full Cascara Sagrada list.

See the full Cascara Sagrada 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
Cascara Sagrada 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 Cascara Sagrada and Acetaminophen, Caffeine, Pyrilamine Together: Common Questions

Can you take Cascara Sagrada 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 2 interactions listed for Cascara Sagrada and Acetaminophen, Caffeine, Pyrilamine?
Acetaminophen, Caffeine, Pyrilamine belongs to more than one drug category, and Cascara Sagrada 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 Cascara Sagrada 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 Cascara Sagrada?

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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.