Peony + Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.
Acetaminophen, Aspirin, Caffeine falls into 3 drug categories that Peony can interact with; the most serious is rated moderate. Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
Read the full interaction reportPeony and Acetaminophen, Aspirin, Caffeine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Peony interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 3 of those categories, so it can interact with Peony in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 3Why this applies to Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Peony interacts with.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect has not been reported in humans.
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.
Here's the piece of this combo that matters: the caffeine in Excedrin is cleared by a liver enzyme called CYP1A2. Lab studies suggest peony may gently slow that enzyme down. In theory, that could let caffeine hang around a little longer, so you might feel more of its effects, things like jitteriness, a racing or pounding heart, trouble sleeping, or feeling wired.
I want to be honest about how soft this evidence is. It comes only from test-tube and animal studies, and it has never been shown to happen in real people. The acetaminophen and aspirin parts aren't really affected by this. If you regularly use both, just mention it to your pharmacist or doctor so they can keep an eye on it.
- Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 3Acetaminophen, Aspirin, Caffeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect has not been reported in humans.
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.
Here's the gist with Excedrin (a combo of acetaminophen, aspirin, and caffeine) and peony root. Lab and animal studies suggest peony may gently slow down a liver enzyme called CYP3A4, which helps clear certain medicines. In theory, that could let some drugs build up a little. For this trio, caffeine is the piece most affected by these pathways, so you might feel slightly more of caffeine's effects, like jitteriness, a racing heart, or trouble sleeping.
That said, this is only a theoretical concern from test-tube data, and it hasn't been seen in real people. It's likely minor for most folks. Still, if you take peony regularly or notice extra jitters, run it by your pharmacist or doctor first.
- Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. PubMed
ANTICOAGULANT/ANTIPLATELET DRUGS
3 of 3Acetaminophen, Aspirin, Caffeine also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects.
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.
The piece of this combo pill that matters here is the aspirin. Aspirin already thins your blood a bit by making your platelets less sticky, which is why it can cause easy bruising, nosebleeds, or stomach irritation. Peony root has been studied in lab and animal research and appears to have its own mild blood-thinning, anti-clotting action. Stack the two together and, in theory, you could see a little more bleeding tendency than from either one alone.
I want to be honest about the strength of this: it's based on test-tube and animal work, not human studies, so it's more of a caution than a proven problem. Still, if you regularly take Excedrin and want to add peony, run it past your pharmacist or doctor first, especially if you bruise easily or take other blood thinners.
- Koo YK, Kim JM, Koo JY, et al. Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa. Pharmazie 2010;65(8):624-8.
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Peony Also Interacts With Other Medications
Peony has 810 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.
Check Another of Your Medications Against Peony
We haven’t checked that one against Peony yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Peony. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine
This page covers Peony 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
Taking Peony as Part of a Dietary Supplement Product? Check It for Interactions
We hold 71 real supplement products containing Peony, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Peony. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Peony — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Peony 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.
#213 of 1,452 supplements looked up here in the last 7 days
#377 of 2,830 medications looked up here in the last 7 days
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.
About Peony
What is Peony?
- Menstrual cramps and irregular periods
- Muscle cramps and spasms
- Anxiety and stress
- Inflammation and pain
- Polycystic ovary syndrome (PCOS)
Peony root is a traditional Chinese medicine herb often used for menstrual problems, cramps, and inflammation, frequently as part of combination formulas. Human evidence for most uses is limited or preliminary, so it should not replace proven treatments. Talk to your pharmacist or doctor before using it, especially if you are pregnant, breastfeeding, or taking other medicines.
Other Drugs & Peony
Browse every other medication we’ve checked against Peony — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
810 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Miconazole ›
- Acetaminophen ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Ketoprofen ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Nortriptyline ›
- Rifampin ›
- Testosterone Undecanoate ›
- Aripiprazole ›
- Bendamustine ›
- Bivalirudin ›
- Caffeine (otc Drug) ›
- Ciclesonide ›
- Clonazepam ›
- Cyclobenzaprine ›
- Dapsone ›
Showing 60 of 810 moderate interactions — see all 810 on the Peony page.
No interaction 2,019 drugs checked — show the list
We also checked Peony against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Metoprolol ›
- Ivermectin ›
- Rosuvastatin ›
- Escitalopram ›
- Valacyclovir ›
- Docusate ›
- Hydroxyurea ›
- Methamphetamine ›
- Semaglutide ›
- Sumatriptan ›
- Tirzepatide ›
- Lisdexamfetamine ›
- Bupropion ›
- Metformin ›
- Acyclovir ›
- Amoxicillin ›
- Lisinopril ›
- Doxycycline ›
- Lamotrigine ›
- Methotrexate ›
- Fluoxetine ›
- Gabapentin ›
- Pregabalin ›
- Amphetamine ›
- Isotretinoin ›
- Azithromycin ›
- Dextroamphetamine ›
- Methylene Blue ›
- Duloxetine ›
- Ciprofloxacin ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Valsartan ›
- Levothyroxine Sodium ›
- Levetiracetam ›
- Mitomycin ›
- Minoxidil ›
- Cefaclor ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Ezetimibe ›
- Levodopa ›
- Vancomycin ›
- Phenylephrine ›
- Spironolactone ›
- Venlafaxine ›
- Dirithromycin ›
Showing the 60 most looked-up of 2,019 medications checked with no known interaction — see the full Peony list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Acetaminophen, Aspirin, Caffeine Is Linked to Lower Levels of 5 Nutrients
Natural Medicines records Acetaminophen, Aspirin, Caffeine as a medicine that can lower these. This is not an interaction with Peony — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Acetaminophen, Aspirin, Caffeine nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Peony and Acetaminophen, Aspirin, Caffeine Together: Common Questions
Can you take Peony with Acetaminophen, Aspirin, Caffeine?
Why are there 3 interactions listed for Peony and Acetaminophen, Aspirin, Caffeine?
How serious is the Peony and Acetaminophen, Aspirin, Caffeine interaction?
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.