Drug & supplement interaction

Tangerine + Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, and others.

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

Tangerine has a minor interaction with Acetaminophen, Butalbital, Caffeine. In vitro, tangeretin, a constituent of tangerine, induces a 52% increase in the metabolism of midazolam by cytochrome P450 3A4 (CYP3A4).

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Tangerine and Acetaminophen, Butalbital, Caffeine

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

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Tangerine interacts with.

In vitro, tangeretin, a constituent of tangerine, induces a 52% increase in the metabolism of midazolam by cytochrome P450 3A4 (CYP3A4). This suggests that tangeretin may stimulate CYP3A4 activity. However, in humans, drinking tangerine juice 200 mL slightly delayed the absorption, but did not affect the metabolism, of midazolam, a CYP3A4 substrate. Theoretically, tangerine juice might increase CYP3A4 activity and decrease levels of drugs metabolized by this enzyme. However, this effect is unlikely.
Some drugs metabolized by CYP3A4 include amitriptyline (Elavil), amiodarone (Cordarone), citalopram (Celexa), felodipine (Plendil), lansoprazole (Prevacid), ondansetron (Zofran), prednisone (Deltasone, Orasone), sertraline (Zoloft), sibutramine (Meridia), and many others.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the gist for your headache combo (acetaminophen, butalbital, and caffeine). A natural compound in tangerine, called tangeretin, slightly sped up the CYP3A4 enzyme in lab dishes. That's one of the pathways your body uses to break down parts of this medication. In theory, a faster enzyme could clear the drug a little quicker, which might make it work a touch less well for tension headaches.

The good news: when this was actually tested in people, drinking tangerine juice barely changed anything. So this is mostly a theoretical, lab-based concern, and eating tangerines as food is very unlikely to weaken your headache relief. If you notice your medication isn't helping like usual, mention it to your pharmacist or doctor rather than adjusting anything yourself.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Backman, J. T., Maenpaa, J., Belle, D. J., Wrighton, S. A., Kivisto, K. T., and Neuvonen, P. J. Lack of correlation between in vitro and in vivo studies on the effects of tangeretin and tangerine juice on midazolam hydroxylation. Clin Pharmacol Ther 2000; 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

Tangerine Also Interacts With Other Medications

Tangerine has 642 minor known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine one above is one of them. If you take anything else, check it against the full list below.

Minor 642 No known interaction 2,188 (incl. Acetaminophen, Butalbital, Caffeine)
Taking anything else?

Check Another of Your Medications Against Tangerine

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine

This page covers Tangerine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine page lists 252 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: 11 major · 197 moderate · 44 minor.

From our pharmacist’s overview on the Acetaminophen, Butalbital, Caffeine page

“Alcohol is the interaction I would flag first for anyone taking acetaminophen, butalbital, and caffeine (Esgic, Fiogesic, and others). Drinking raises the risk of liver injury from the acetaminophen component, and 38 of the 252 supplement ingredients on file carry that same liver concern.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Butalbital, Caffeine interaction page

One more smart check

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

We hold 705 real supplement products containing Tangerine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Tangerine. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Tangerine — 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 Tangerine and Acetaminophen, Butalbital, Caffeine 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 Tangerine
Top 25%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine
Top 1%

#26 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 Tangerine

What is Tangerine?

  • Source of vitamin C
  • Digestive support
  • Aromatherapy and relaxation
  • Cough and phlegm (traditional)
  • Skin and flavoring uses

Tangerine is a sweet citrus fruit that is a good source of vitamin C and other nutrients, and is widely enjoyed as food. While the peel and essential oil are used in traditional medicine and aromatherapy, strong human evidence for specific health benefits beyond basic nutrition is limited. Enjoying tangerines as part of a balanced diet is generally safe for most people.

Read the full Tangerine monograph & all interactions
Medication

About Acetaminophen, Butalbital, and Caffeine

What Is Acetaminophen, Butalbital, and Caffeine Used For?

Brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, Esgic, Fioricet

This combination product — available as capsules, tablets, and oral solution under various names including Fioricet — is used to relieve the symptoms of tension headaches (also called muscle contraction headaches).

All supported products, including Fioricet capsules and the oral solution, share this same indication. Because butalbital can be habit-forming, extended or repeated use is not recommended, and these products are not established as safe or effective for treating headaches that come back frequently over time.

See full Acetaminophen, Butalbital, and Caffeine drug information
Keep checking

Other Drugs & Tangerine

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

0Major
0Moderate
642Minor
2,187No known interaction
642 Minor 2,187 No interaction
Minor

642 interactions

Showing 60 of 642 minor interactions — see all 642 on the Tangerine page.

No interaction 2,187 drugs checked — show the list

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

Showing the 60 most looked-up of 2,187 medications checked with no known interaction — see the full Tangerine list.

See the full Tangerine interactions page
See every supplement checked against Acetaminophen, Butalbital, Caffeine, 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
Tangerine monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Caffeine supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Caffeine, ranked by severity Acetaminophen, Butalbital, and Caffeine drug information › The full plain-English guide to this medication 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 Tangerine and Acetaminophen, Butalbital, Caffeine Together: Common Questions

Can you take Tangerine with Acetaminophen, Butalbital, Caffeine?
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.
How serious is the Tangerine and Acetaminophen, Butalbital, Caffeine 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

Still Have a Question About Acetaminophen, Butalbital, Caffeine and Tangerine?

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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.