Drug & supplement interaction

Sweet Annie + Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.

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

Acetaminophen, Aspirin, Caffeine falls into 2 drug categories that Sweet Annie can interact with; the most serious is rated moderate. Theoretically, concomitant use might have additive adverse hepatotoxic effects.

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

Sweet Annie and Acetaminophen, Aspirin, Caffeine

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

Why Are There 2 Interactions?

Sweet Annie interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 2 of those categories, so it can interact with Sweet Annie 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, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under HEPATOTOXIC DRUGS — the group Sweet Annie interacts with.

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
There is some concern that Sweet Annie can adversely affect the liver.
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 simple version: one of the ingredients in Excedrin is acetaminophen (the same medicine in Tylenol), and acetaminophen is hard on the liver when you take a lot of it. There's some concern that Sweet Annie may also be tough on the liver. So the worry is that the two together could add up and put extra strain on that organ.

I want to be honest about the strength of this, though. This is mostly theoretical and based on scattered reports, not solid studies. For most people taking Excedrin at normal doses, this isn't a big alarm. Still, watch for signs like yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and check with your pharmacist or doctor before combining them, especially if you drink alcohol or have liver issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Centers for Disease Control and Prevention (CDC). Hepatitis temporally associated with an herbal supplement containing artemisinin-Washington, 2008. MMWR Morb Mortal Wkly Rep 2009;58:854-8.
  2. Savage RL, Hill GR, Barnes J, Kenyon SH, Tatley MV. Suspected hepatotoxicity with a supercritical carbon dioxide extract of Artemisia annua in grapeseed oil used in New Zealand. Front Pharmacol. 2019;10:1448. PubMed
  3. Ruperti-Repilado FJ, Haefliger S, Rehm S, et al. Danger of herbal tea: a case of acute cholestatic hepatitis due to Artemisia annua tea. Front Med (Lausanne). 2019;6:221. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Aspirin, Caffeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Sweet Annie may alter plasma levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that the Sweet Annie constituent artemisinin induces CYP3A4, possibly increasing CYP3A4 activity by 1.9-fold. However, Sweet Annie extract seems to inhibit the activity of CYP3A4 in vitro, suggesting that other constituents of Sweet Annie play a role in its effects on the overall activity of this enzyme. More information is needed to determine whether taking Sweet Annie extract affects the metabolism of CYP3A4 substrates.
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 honest picture with Sweet Annie and a combo product like Excedrin (acetaminophen, aspirin, and caffeine). The concern on file is about CYP3A4, a liver enzyme. The catch is that lab studies pull in two directions: artemisinin (from Sweet Annie) may speed this enzyme up, while the whole plant extract may slow it down. So we genuinely don't know the net effect in real people yet.

On top of that, these three ingredients aren't mainly handled by CYP3A4 anyway. Caffeine leans on CYP1A2, and acetaminophen and aspirin clear through other routes. So a big, predictable change here is unlikely. This is theoretical, test-tube level evidence, so I wouldn't lose sleep over it. Still, if you use Sweet Annie regularly, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Xing J, Kirby BJ, Whittington D, et al. Evaluation of P450 inhibition and induction by artemisinin antimalarials in human liver microsomes and primary human hepatocytes. Drug Metabl Dispos 2012;40(9):1757-64. PubMed
  2. Kane NF, Kiani BH, Desrosiers MR, Towler MJ, Weathers PJ. Artemisia extracts differ from artemisinin effects on human hepatic CYP450s 2B6 and 3A4 in vitro. J Ethnopharmacol 2022. DOI

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 Annie Also Interacts With Other Medications

Sweet Annie has 888 moderate known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is among them. If you take anything else, check it against the full list below.

Moderate 888 No known interaction 1,942 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Sweet Annie

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Sweet Annie only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 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 Ephedra (major).

By severity: 13 major · 312 moderate · 46 minor.

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

“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Aspirin, Caffeine interaction page

One more smart check

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

We hold 243 real supplement products containing Sweet Annie, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sweet Annie. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Sweet Annie — 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 Annie and Acetaminophen, Aspirin, 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 Annie
Top half

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

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 10

#7 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 Annie

What is Sweet Annie?

Sweet Annie
  • Malaria (traditional)
  • Fever
  • Inflammation
  • Digestive complaints
  • Antimicrobial support
  • Insect repellent

Sweet Annie (Artemisia annua) is the source of artemisinin, a compound used in prescription antimalarial drugs. While the purified drug is well studied for malaria, the herb itself as a supplement is not proven for the wide range of conditions people use it for, and self-treating malaria with the raw herb is dangerous. Talk to a pharmacist or doctor before using it.

Read the full Sweet Annie monograph & all interactions
Keep checking

Other Drugs & Sweet Annie

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

0Major
888Moderate
0Minor
1,941No known interaction
888 Moderate 1,941 No interaction
Moderate

888 interactions

Showing 60 of 888 moderate interactions — see all 888 on the Sweet Annie page.

No interaction 1,941 drugs checked — show the list

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

Showing the 60 most looked-up of 1,941 medications checked with no known interaction — see the full Sweet Annie list.

See the full Sweet Annie interactions page
See every supplement checked against Acetaminophen, Aspirin, 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 Annie monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Aspirin, Caffeine supplement interactions › Every supplement checked against Acetaminophen, Aspirin, Caffeine, 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 Sweet Annie and Acetaminophen, Aspirin, Caffeine Together: Common Questions

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

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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.