Drug & supplement interaction

Hibiscus Sabdariffa + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 5 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
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Hibiscus Sabdariffa and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Hibiscus Sabdariffa interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 5 of those categories, so it can interact with Hibiscus Sabdariffa in 5 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 5

Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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

This combination product packs in several ingredients, but the piece that matters for hibiscus is the caffeine. Caffeine is cleared from your body mainly by a liver enzyme called CYP1A2. Lab studies suggest concentrated hibiscus extract might slow that enzyme down a bit. In theory, that could let caffeine linger a little longer, which for some folks means feeling jittery, a racing heart, or trouble sleeping.

Here's the reassuring part: this is only a theoretical concern from test-tube research. It has never been reported in real people, and a cup or two of hibiscus tea is unlikely to cause any noticeable problem. If you use strong hibiscus supplements regularly, just mention it to your pharmacist or doctor so they can keep an eye on things.

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 5

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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

This combination product has one ingredient worth flagging here: hydrocodone. Hydrocodone is a prodrug that the liver enzyme CYP2D6 converts into its more potent form. Lab studies suggest hibiscus extract may block CYP2D6 a little. If that happened in real life, you would expect slightly less conversion to the active painkiller, so the pain or cough relief could feel a touch weaker, not stronger.

Honestly, this is only a theory based on test-tube data, and it has never been shown to matter in people. A cup of tart hibiscus tea is very unlikely to cause trouble. Concentrated hibiscus supplements are the bigger unknown, so if you take those 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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 5

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP3A4 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP3A4. 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

This combo product (Hycomine Compound) contains hydrocodone, an opioid that your liver partly handles using an enzyme called CYP3A4. In lab dish studies, concentrated hibiscus extract has slowed that same enzyme down a bit. The catch: this has only been seen in test tubes, never in actual people, so we're really talking about a theoretical concern here.

If it did happen, the idea is that hydrocodone might clear a touch slower and build up slightly, which could mean a little more drowsiness, dizziness, or constipation. A cup or two of hibiscus tea is very unlikely to cause trouble. Concentrated hibiscus capsules are the bigger question mark. If you use those regularly, just give your pharmacist or doctor a quick heads-up so they can keep an eye on things.

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)

4 of 5
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

This combo product (Hycomine Compound) contains several active ingredients, but the interaction we're talking about applies only to the acetaminophen piece. Hibiscus, usually sipped as a tart red tea, seems to make your body clear acetaminophen a little faster. In a small study, drinking a hibiscus beverage shortened how long acetaminophen stuck around in the body.

In plain terms, your pain or fever relief from the acetaminophen part might wear off a touch sooner. This is rated minor, and honestly the real-world impact is unknown. The hydrocodone, caffeine, chlorpheniramine, and phenylephrine ingredients aren't part of this interaction. A casual cup of hibiscus tea probably isn't a concern, but if you're using concentrated hibiscus supplements, check with your pharmacist or doctor first.

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

5 of 5

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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

This combination product (Hycomine Compound) contains acetaminophen, which is the piece that connects to this interaction. A small portion of acetaminophen is handled by a liver enzyme called CYP2E1, and that pathway is what turns a tiny amount of it into a byproduct that can stress the liver. Lab (test-tube) studies suggest hibiscus may gently slow CYP2E1. In theory, that could shift how a little acetaminophen is processed.

Here's the honest part: this is theoretical only and has never been seen in real people. Occasional hibiscus tea is very unlikely to matter. The bigger, well-known caution is simply not exceeding the acetaminophen dose. If you take 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.

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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Hibiscus Sabdariffa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.

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

“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page

How much people look this up

Where Hibiscus Sabdariffa and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 Hibiscus Sabdariffa
Top 25%

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

29 days ago today
Medication Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Top 5%

#69 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, Caffeine, Chlorpheniramine, Hydrocodone, 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
Hibiscus Sabdariffa monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 Hibiscus Sabdariffa and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions

Can you take Hibiscus Sabdariffa with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
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 5 interactions listed for Hibiscus Sabdariffa and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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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