Drug & supplement interaction

Peony + Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine brand names: Norgesic Forte, Invagesic, Invagesic Forte, Orphengesic, Norgesic, and others.

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

Aspirin, Caffeine, Orphenadrine 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 report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peony and Aspirin, Caffeine, Orphenadrine

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. Aspirin, Caffeine, Orphenadrine 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).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Peony interacts with.

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
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.
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

This combo pill includes caffeine, which your body clears using a liver enzyme called CYP1A2. In lab and animal studies, peony appears to weakly slow that same enzyme. In theory, that could let caffeine hang around a bit longer, so you might notice more of the usual caffeine effects: jitteriness, a racing or pounding heart, trouble sleeping, or feeling wired. The aspirin and orphenadrine pieces aren't really driven by this enzyme.

Here's the honest part: this is only a theoretical, test-tube finding, and it hasn't been shown in real people. Everyday food amounts of peony are unlikely to matter. Still, if you take concentrated peony supplements regularly, mention it to your pharmacist or doctor so they can keep an eye on it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

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

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
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.
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

This combo pill mixes aspirin, caffeine, and a muscle relaxer called orphenadrine. The piece that matters here is orphenadrine, which your body partly clears using a liver enzyme known as CYP3A4. In lab dish studies, peony seems to mildly slow that same enzyme. If that carried over into people, orphenadrine could hang around a bit longer and feel stronger, meaning more chance of dry mouth, blurry vision, dizziness, drowsiness, or a fast heartbeat (which the caffeine could add to).

I want to be honest though: this is only theoretical, based on test-tube and animal work, not real patients. So it's a maybe, not a sure thing. If you'd like to use peony alongside this medicine, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 3

Aspirin, Caffeine, Orphenadrine also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects.
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

This combination product contains aspirin, which is the piece that matters here. Aspirin already thins your blood by making platelets less sticky, which is why it can cause bruising, nosebleeds, or stomach irritation. Peony root has shown some blood-thinning and antiplatelet activity too, so pairing the two could, in theory, add up and raise your bleeding risk a bit.

I want to be honest about the evidence: this concern comes only from lab and animal studies, not from real-world human reports, so it's more of a caution than a proven problem. Still, if you take aspirin daily and want to add a peony supplement, check with your pharmacist or doctor first, and watch for easy bruising or bleeding that won't stop.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.

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

Peony Also Interacts With Other Medications

Peony has 810 moderate known drug interactions in our database — the Aspirin, Caffeine, Orphenadrine one above is among them. If you take anything else, check it against the full list below.

Moderate 810 No known interaction 2,020 (incl. Aspirin, Caffeine, Orphenadrine)
Taking anything else?

Check Another of Your Medications Against Peony

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine

This page covers Peony only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Orphenadrine page lists 350 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: 14 major · 289 moderate · 47 minor.

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

“Aspirin, caffeine, and orphenadrine (the Norgesic and Orphengesic brands) come with a supplement list that deserves real vigilance, with 14 of its 350 entries rated major. Over 200 of those ingredients can add to aspirin's effect on platelets and raise bleeding risk, another 44 stack stimulant effects on top of the caffeine, and grapef…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Orphenadrine interaction page

One more smart check

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 Aspirin, Caffeine, Orphenadrine 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:

How much people look this up

Where Peony and Aspirin, Caffeine, Orphenadrine 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 Peony
Top 25%

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

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Top 5%

#116 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 Peony

What is Peony?

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.

Read the full Peony monograph & all interactions
Keep checking

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.

0Major
810Moderate
0Minor
2,019No known interaction
810 Moderate 2,019 No interaction
Moderate

810 interactions

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.

Showing the 60 most looked-up of 2,019 medications checked with no known interaction — see the full Peony list.

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

Can you take Peony with Aspirin, Caffeine, Orphenadrine?
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 3 interactions listed for Peony and Aspirin, Caffeine, Orphenadrine?
Aspirin, Caffeine, Orphenadrine belongs to more than one drug category, and Peony 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 Peony and Aspirin, Caffeine, Orphenadrine 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.