Drug & supplement interaction

Sweet Clover + Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen brand name: Combogesic.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Ibuprofen falls into 2 drug categories that Sweet Clover can interact with; the most serious is rated moderate. Theoretically, concomitant use of sweet clover with hepatoxic drugs might increase the risk of hepatotoxicity.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sweet Clover and Acetaminophen, Ibuprofen

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Sweet Clover interacts with whole categories of medication. Acetaminophen, Ibuprofen falls into 2 of those categories, so it can interact with Sweet Clover in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen 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 concern with Combogesic, which combines acetaminophen and ibuprofen. The acetaminophen part is one of the better-known medicines that can stress the liver, especially at higher doses or with regular alcohol use. Sweet clover contains coumarin, and in large or concentrated amounts it has been linked, in rare cases, to mild liver irritation on its own.

The worry is simply that two things that can each nudge the liver might add up. To be honest, this is a theoretical interaction based on how these substances behave, not on strong studies, so I don't want to alarm you. Still, if you take Combogesic regularly, it's worth running the sweet clover past your pharmacist or doctor first, and never exceed the acetaminophen dose on the label.

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
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

Acetaminophen, Ibuprofen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, fresh sweet clover might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Fresh sweet clover contains coumarinic acids, which are converted to free coumarins during drying. Dicoumarol, which has anticoagulant activity, also has been found in some sweet clover preparations and can be formed if fresh sweet clover is allowed to spoil.
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 with Combogesic: it pairs acetaminophen with ibuprofen, and ibuprofen is an NSAID. NSAIDs already nudge up your bleeding risk a bit, partly because they can irritate the stomach lining and partly because they make platelets a little less sticky. Sweet clover comes into play because it contains coumarin, and if the plant has spoiled or fermented it can form dicoumarol, which thins the blood much like warfarin does.

So stacking the two could, in theory, mean more bruising, nosebleeds, or stomach bleeding. To be fair, this is a theoretical concern based on the herb's chemistry, not strong human studies, and quality fresh product matters a lot. Still, please run it by your pharmacist or doctor before combining them.

References
  1. Monographs on the medicinal uses of plant drugs. Exeter, UK: European Scientific Co-op Phytother, 1997.
  2. Wichtl MW. Herbal Drugs and Phytopharmaceuticals. Ed. N.M. Bisset. Stuttgart: Medpharm GmbH Scientific Publishers, 1994.
  3. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

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 479 moderate known drug interactions in our database — the Acetaminophen, Ibuprofen one above is among them. If you take anything else, check it against the full list below.

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, Ibuprofen

This page covers Sweet Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Ibuprofen page lists 342 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), Danshen (major) and Piracetam (major).

By severity: 7 major · 290 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Ibuprofen page

“Combogesic pairs acetaminophen with ibuprofen, so it inherits the vulnerabilities of both drugs, and its supplement list deserves real attention before you add anything to it. Of the 342 ingredients on file, 7 carry a major rating, and those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Ibuprofen 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, Ibuprofen 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, Ibuprofen 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

#1,385 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Ibuprofen
Top 25%

#417 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
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
479Moderate
0Minor
2,350No known interaction
Moderate

479 interactions

Showing 60 of 479 moderate interactions — see all 479 on the Sweet Clover page.

No interaction 2,350 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Sweet Clover and Acetaminophen, Ibuprofen Together: Common Questions

Can you take Sweet Clover with Acetaminophen, Ibuprofen?
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.
Why are there 2 interactions listed for Sweet Clover and Acetaminophen, Ibuprofen?
Acetaminophen, Ibuprofen belongs to more than one drug category, and Sweet Clover 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 Sweet Clover and Acetaminophen, Ibuprofen 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

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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.