Drug & supplement interaction

Adenosine + Aspirin, Caffeine, Orphenadrine

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

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

Adenosine has a minor interaction with Aspirin, Caffeine, Orphenadrine. Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.

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

Adenosine and Aspirin, Caffeine, Orphenadrine

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

Minor

METHYLXANTHINES

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under METHYLXANTHINES — the group Adenosine interacts with.

Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.
The methylxanthines, aminophylline, caffeine, and theophylline, can block the effects of adenosine by acting as competitive antagonists at adenosine cell surface receptors. It is recommended that methylxanthines be avoided for 24 hours prior to cardiac stress tests.
Severity Minor 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 focus on with your Norgesic tablet: it contains caffeine, and caffeine is a member of a family called methylxanthines. Caffeine and adenosine work against each other. Caffeine sits on the same cell receptors adenosine wants to use and blocks them, so taking an adenosine supplement alongside caffeine means the caffeine can blunt whatever effect the adenosine might have, and vice versa.

In real life this is a minor, theory-based concern based on how these molecules behave, not on reports of people getting hurt. The amount of caffeine in these combo pills is modest. One practical note: if your doctor ever schedules a cardiac stress test, both caffeine and adenosine matter there, so mention them. When in doubt, check with your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Eisenach JC, Curry R, Hood DD. Dose response of intrathecal adenosine in experimental pain and allodynia. Anesthesiology 2002;97:938-42.. PubMed
  2. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. 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

Adenosine Also Interacts With Other Medications

Adenosine has 2 major, 1 moderate, 43 minor known drug interactions in our database — the Aspirin, Caffeine, Orphenadrine one above is one of them. If you take anything else, check it against the full list below.

Major 2 Moderate 1 Minor 43 No known interaction 2,784 (incl. Aspirin, Caffeine, Orphenadrine)
Taking anything else?

Check Another of Your Medications Against Adenosine

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine

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

We hold 66 real supplement products containing Adenosine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Adenosine. Your product may carry other ingredients that interact with Aspirin, Caffeine, Orphenadrine too, on top of Adenosine — 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 Adenosine 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 Adenosine
Top half

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

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Top 25%

#592 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 Adenosine

What is Adenosine?

Adenosine
  • Energy and cellular function support
  • Athletic performance and muscle energy
  • Circulation support
  • General wellness

Adenosine is a natural building block your body uses for energy and cell signaling, and a prescription injectable version is used by doctors to treat certain fast heart rhythms. As an over-the-counter supplement (often sold as AMP or ATP), there is little strong evidence that swallowing it boosts energy or performance, and quality can vary. Talk to your pharmacist before using adenosine supplements, especially if you have a heart condition.

Read the full Adenosine monograph & all interactions
Keep checking

Other Drugs & Adenosine

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

2Major
1Moderate
43Minor
2,783No known interaction
2 Major 1 Moderate 43 Minor 2,783 No interaction
Major

2 interactions

Moderate

1 interaction

Minor

43 interactions

No interaction 2,783 drugs checked — show the list

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

Showing the 60 most looked-up of 2,783 medications checked with no known interaction — see the full Adenosine list.

See the full Adenosine 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
Adenosine 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 Adenosine and Aspirin, Caffeine, Orphenadrine Together: Common Questions

Can you take Adenosine with Aspirin, Caffeine, Orphenadrine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Adenosine and Aspirin, Caffeine, Orphenadrine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Aspirin, Caffeine, Orphenadrine and Adenosine?

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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.