Drug & supplement interaction

Saffron + Acetaminophen, Butalbital, Caffeine

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

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

Saffron has a moderate interaction with Acetaminophen, Butalbital, Caffeine. Theoretically, saffron might inhibit the metabolism of caffeine.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceB
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Saffron and Acetaminophen, Butalbital, Caffeine

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

Moderate

CAFFEINE

Why this applies to Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine falls under CAFFEINE — the group Saffron interacts with.

Theoretically, saffron might inhibit the metabolism of caffeine.
A small clinical study suggests that taking saffron powder 300 mg in 150 mL water daily for 5 days and then taking caffeine 200 mg seems to reduce caffeine metabolite levels in the saliva and urine in males, but not females. Theoretically, this may be due to the inhibition of cytochrome P450 1A2 by saffron.
Severity Moderate Likelihood Possible Evidence B

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 piece to pay attention to with this headache combo: it contains caffeine. There's some early evidence that saffron supplements may slow down how your body clears caffeine (by gently blocking a liver enzyme called CYP1A2). If caffeine hangs around longer, you could feel more of its usual effects, like jitteriness, a racing or pounding heartbeat, trouble sleeping, or feeling wired.

The good news: this is fairly mild and not fully proven. The small study used concentrated saffron daily, not the pinch you'd use in cooking, and it only showed up in men, not women. The butalbital and acetaminophen pieces aren't really affected here. If you take saffron supplements regularly, just give your pharmacist or doctor a heads-up so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Begas E, Bounitsi M, Kilindris T, et al. Effects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers. Food Chem Toxicol. 2019;130:32-43. 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

Saffron Also Interacts With Other Medications

Saffron has 520 moderate 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.

Moderate 520 No known interaction 2,310 (incl. Acetaminophen, Butalbital, Caffeine)
Taking anything else?

Check Another of Your Medications Against Saffron

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

From our Q&A

Questions About Saffron or Acetaminophen, Butalbital, Caffeine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Saffron or Acetaminophen, Butalbital, Caffeine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine

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

We hold 418 real supplement products containing Saffron, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Saffron. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Saffron — 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 Saffron 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 Saffron
Top 25%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine
Steady interest

#1,692 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 Saffron

What is Saffron?

Saffron
  • Depression and low mood
  • Anxiety
  • PMS symptoms
  • Memory and cognition
  • Eye health (age-related macular degeneration)

Saffron is a costly spice that has shown promise in early studies for mild-to-moderate depression and some mood and PMS symptoms, but most research uses small trials, so results are not definitive. It is generally well tolerated in food and small supplement amounts, but high doses can be harmful and it should be avoided in pregnancy. Talk to your pharmacist or doctor before using saffron supplements.

Read the full Saffron 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 three-ingredient combination — butalbital, acetaminophen, and caffeine — is used to relieve the symptoms of tension headache (also called muscle contraction headache). All supported products, including tablets, capsules, and oral solution, share this same approved use.

It is worth knowing that evidence for using this combination to treat repeated, frequent tension headaches over time is limited. Because butalbital can be habit-forming, extended or repeated use is not recommended.

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

Other Drugs & Saffron

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

0Major
520Moderate
0Minor
2,309No known interaction
520 Moderate 2,309 No interaction
Moderate

520 interactions

Showing 60 of 520 moderate interactions — see all 520 on the Saffron page.

No interaction 2,309 drugs checked — show the list

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

Showing the 60 most looked-up of 2,309 medications checked with no known interaction — see the full Saffron list.

See the full Saffron 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
Saffron 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 Saffron and Acetaminophen, Butalbital, Caffeine Together: Common Questions

Can you take Saffron with Acetaminophen, Butalbital, Caffeine?
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 Saffron and Acetaminophen, Butalbital, Caffeine 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, Butalbital, Caffeine and Saffron?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.