Drug & supplement interaction

Hibiscus Sabdariffa + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Acetaminophen, Butalbital, Codeine Phosphate falls into 4 drug categories that Hibiscus Sabdariffa can interact with; the most serious is rated minor. Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP1A2 substrates.

Read the full interaction report
SeverityMinor
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Hibiscus Sabdariffa and Acetaminophen, Butalbital, Codeine Phosphate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Hibiscus Sabdariffa interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine Phosphate falls into 4 of those categories, so it can interact with Hibiscus Sabdariffa in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 4

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Hibiscus Sabdariffa interacts with.

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP1A2 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP1A2. This interaction has not been reported in humans.
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

Here's the honest picture: this concern comes only from lab dish research, where hibiscus extract slowed down an enzyme called CYP1A2. That's listed as a possible interaction for this combo pill (acetaminophen, butalbital, and codeine), but it has never actually been seen in people. So I wouldn't lose sleep over it.

If hibiscus did slow that enzyme even a little, drugs cleared by it could build up slightly, which in theory might mean a touch more drowsiness or grogginess. In real life, a cup or two of hibiscus tea is very unlikely to matter. Concentrated hibiscus supplements are the bigger question mark. Since this medicine already causes sleepiness and can be habit-forming, just run any hibiscus supplement past your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Johnson SS, Oyelola FT, Ari T, Juho H. In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family Malvaceae) on selected cytochrome P450 isoforms. Afr J Tradit Complement Altern Med. 2013 Apr 12;10(3):533-40.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 4

Acetaminophen, Butalbital, Codeine Phosphate also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2D6 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2D6. This interaction has not been reported in humans.
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

Here's the interesting wrinkle with this combo. The codeine part of Phrenilin #3 is actually a prodrug, meaning your body has to convert it into morphine using an enzyme called CYP2D6 before it does much for pain. Lab studies suggest hibiscus may gently slow that same enzyme. If that happened in real life, you could get less pain relief from the codeine, not more, because less of it would turn into the active form.

The honest truth is this is theoretical. It's only been seen in a test tube, never in people, and it's rated a minor concern. A cup or two of hibiscus tea almost certainly won't matter. If you're using concentrated hibiscus supplements regularly, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Johnson SS, Oyelola FT, Ari T, Juho H. In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family Malvaceae) on selected cytochrome P450 isoforms. Afr J Tradit Complement Altern Med. 2013 Apr 12;10(3):533-40.
Minor

ACETAMINOPHEN (Tylenol, others)

3 of 4
Theoretically, taking Hibiscus sabdariffa with acetaminophen might decrease the clinical effects of acetaminophen.
There is some evidence that consuming a Hibiscus sabdariffa beverage (Zobo drink) before taking acetaminophen can decrease the elimination half-life of acetaminophen. Hibiscus sabdariffa does not seem to decrease maximum concentration or area under the curve of acetaminophen. The clinical significance of this is unknown.
Severity Minor Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Your medication is a combination of three things, but this interaction only touches the acetaminophen (Tylenol) piece. Some research found that drinking hibiscus (a Zobo-style drink) before taking acetaminophen may make your body clear it a little faster, shortening how long it sticks around. In plain terms, the pain-relieving and fever-lowering benefit from the Tylenol part could be a touch weaker or shorter-lived.

Honestly, this is a minor and mostly theoretical finding. The peak level and total amount your body absorbs didn't really change, so no one knows if it matters in real life. The butalbital and codeine portions aren't part of this interaction at all. An occasional cup of hibiscus tea is very unlikely to cause trouble, but if you use concentrated hibiscus supplements regularly, mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa water extract) on pharmacokinetics of acetaminophen in human volunteers. Eur J Drug Metab Pharmacokinet 2004;29:25-9.
Minor

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

4 of 4

Acetaminophen, Butalbital, Codeine Phosphate also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2E1 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2E1. This interaction has not been reported in humans.
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

The piece worth talking about here is the acetaminophen (Tylenol) part of this combination pill. Acetaminophen is partly handled by a liver enzyme called CYP2E1, which can turn a small amount of it into a byproduct that's hard on the liver. Lab (test tube) studies suggest hibiscus may gently slow this enzyme down. In theory, that could mean a touch less of that harmful byproduct, so this is not a scary or dangerous combination.

That said, this has never actually been shown to happen in people, so it's purely theoretical and rated as minor. Enjoy hibiscus tea if you like it. The bigger, real-world rule with this medication is simply not to exceed the acetaminophen limit and to go easy on alcohol. If you're using concentrated hibiscus supplements, just mention it to your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Johnson SS, Oyelola FT, Ari T, Juho H. In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family Malvaceae) on selected cytochrome P450 isoforms. Afr J Tradit Complement Altern Med. 2013 Apr 12;10(3):533-40.

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

Hibiscus Sabdariffa Also Interacts With Other Medications

Hibiscus Sabdariffa has 2 major, 266 moderate, 818 minor known drug interactions in our database — the Acetaminophen, Butalbital, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.

Major 2 Moderate 266 Minor 818 No known interaction 1,744 (incl. Acetaminophen, Butalbital, Codeine Phosphate)
Taking anything else?

Check Another of Your Medications Against Hibiscus Sabdariffa

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Codeine Phosphate

This page covers Hibiscus Sabdariffa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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).

Open the Acetaminophen, Butalbital, Codeine Phosphate interaction page

How much people look this up

Where Hibiscus Sabdariffa and Acetaminophen, Butalbital, Codeine Phosphate 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 Hibiscus Sabdariffa
Top half

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,740 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 Hibiscus Sabdariffa

What is Hibiscus Sabdariffa?

Hibiscus Sabdariffa
  • High blood pressure
  • Heart and cholesterol health
  • Digestive upset
  • Antioxidant support
  • Fever and general wellness

Hibiscus sabdariffa is a tart, cranberry-flavored plant most often consumed as a tea, and its best-studied use is for mildly lowering blood pressure. Evidence for other uses is limited, and while hibiscus tea is generally well tolerated in food amounts, concentrated supplements should be used cautiously and avoided in pregnancy. Talk to your pharmacist or doctor before using it for a medical condition.

Read the full Hibiscus Sabdariffa monograph & all interactions
Keep checking

Other Drugs & Hibiscus Sabdariffa

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

2Major
266Moderate
818Minor
1,743No known interaction
2 Major 266 Moderate 818 Minor 1,743 No interaction
Major

2 interactions

Moderate

266 interactions

Showing 60 of 266 moderate interactions — see all 266 on the Hibiscus Sabdariffa page.

Minor

818 interactions

Showing 60 of 818 minor interactions — see all 818 on the Hibiscus Sabdariffa page.

No interaction 1,743 drugs checked — show the list

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

Showing the 60 most looked-up of 1,743 medications checked with no known interaction — see the full Hibiscus Sabdariffa list.

See the full Hibiscus Sabdariffa interactions page
See every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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
Hibiscus Sabdariffa monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Codeine Phosphate supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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 Hibiscus Sabdariffa and Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Hibiscus Sabdariffa with Acetaminophen, Butalbital, Codeine Phosphate?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 4 interactions listed for Hibiscus Sabdariffa and Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate belongs to more than one drug category, and Hibiscus Sabdariffa 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 Hibiscus Sabdariffa and Acetaminophen, Butalbital, Codeine Phosphate interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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.