Drug & supplement interaction

Sweet Clover + Acetaminophen, Butalbital, Caffeine

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

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

Sweet Clover has a moderate interaction with Acetaminophen, Butalbital, Caffeine. Theoretically, concomitant use of sweet clover with hepatoxic drugs might increase the risk of hepatotoxicity.

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

Sweet Clover and Acetaminophen, Butalbital, Caffeine

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

Moderate

HEPATOTOXIC DRUGS

Why this applies to Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine falls under HEPATOTOXIC DRUGS — the group Sweet Clover interacts with.

Theoretically, concomitant use of sweet clover with hepatoxic drugs might increase the risk of hepatotoxicity.
Orally, large amounts of sweet clover can cause transient liver injury in susceptible individuals, possibly due to coumarin content. In one case report, a patient with multiple sclerosis developed jaundiced palms and a slight elevation in serum alanine aminotransferase (ALT) after taking sweet clover containing coumarin 10 mg daily for 3 years. Two weeks after starting therapy with subcutaneous interferon (IFN)-beta 1b, aspartate transaminase (AST) and ALT levels increased to 7 and 17 times the upper limit of normal, respectively. Levels normalized after discontinuation of both products. Subsequent use of IFN-beta 1a alone, without sweet clover, resulted in only a very slight increase in AST.
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 to keep an eye on with this combo: the acetaminophen part of your headache pill is processed by your liver, and too much of it is one of the most common causes of liver strain. Sweet clover contains coumarin, which in larger or spoiled doses can also be hard on the liver. Stack the two and you may be giving your liver extra work to do at the same time.

I want to be honest about how strong this evidence is. It's mostly theoretical, based on how these things behave plus a single case report, not solid proof. Still, since both can affect the same organ, it's worth a quick chat with your pharmacist or doctor before combining them, especially if you drink alcohol, take acetaminophen often, or already have liver concerns.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  2. Tamura S, Warabi Y, Matsubara S. Severe liver dysfunction possibly caused by the combination of interferon beta-1b therapy and melilot (sweet clover) supplement. J Clin Pharm Ther 2012;37(6):724-5. 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

Sweet Clover Also Interacts With Other Medications

Sweet Clover has 481 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 481 No known interaction 2,349 (incl. Acetaminophen, Butalbital, Caffeine)
Taking anything else?

Check Another of Your Medications Against Sweet Clover

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine

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

We hold 26 real supplement products containing Sweet Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sweet Clover. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Sweet Clover — 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 Sweet Clover 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 Sweet Clover
Steady interest

#1,122 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine
Top 5%

#64 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 Sweet Clover

What is Sweet Clover?

Sweet Clover
  • Varicose veins and poor circulation
  • Leg swelling (edema)
  • Hemorrhoids
  • Bruising and minor inflammation
  • Respiratory complaints

Sweet clover is a traditional European herb most often promoted for vein problems and leg swelling, but high-quality human evidence is limited. It contains coumarin, which can become dangerous if the plant spoils, so quality matters and you should talk to a pharmacist before using it.

Read the full Sweet Clover 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 & Sweet Clover

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

0Major
481Moderate
0Minor
2,348No known interaction
481 Moderate 2,348 No interaction
Moderate

481 interactions

Showing 60 of 481 moderate interactions — see all 481 on the Sweet Clover page.

No interaction 2,348 drugs checked — show the list

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

Showing the 60 most looked-up of 2,348 medications checked with no known interaction — see the full Sweet Clover list.

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

Can you take Sweet Clover 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 Sweet Clover 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 Sweet Clover?

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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.