Drug & supplement interaction

Vitamin E + 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 2 drug categories that Vitamin E can interact with; the most serious is rated moderate. Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.

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

Vitamin E and Aspirin, Caffeine, Orphenadrine

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Vitamin E interacts with.

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.
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 gist with this combo product (aspirin, caffeine, and the muscle relaxant orphenadrine). On paper, high-dose vitamin E might nudge a liver enzyme called CYP3A4 to work a little faster. If that happened, your body could clear the orphenadrine part a bit quicker, which in theory might make it slightly less effective for easing muscle pain and tension. The aspirin and caffeine pieces aren't really driven by this enzyme, so the effect, if any, would be on the orphenadrine.

I want to be honest: this is only a theoretical concern based on how things work in the lab, not something proven in real patients. One thing worth more attention is that both vitamin E (in high doses) and aspirin can thin the blood, so together they may raise bleeding or bruising risk. If you take vitamin E daily, just mention it to your pharmacist or doctor so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Landes N, Pfluger P, Kluth D, et al. Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol 2003;65:269-73. . PubMed
  2. Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737-40. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

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

Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.
Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors. These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily. Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol. RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors. Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.
Severity Moderate Likelihood Possible Evidence B

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 know about this combo product: the aspirin part already thins your blood by keeping platelets from clumping together. Vitamin E does something similar, and in higher doses it can also work against vitamin K, which your body needs to form clots. So stacking the two can nudge your bleeding risk up a bit more than aspirin alone.

In real life that might look like easier bruising, nosebleeds, bleeding gums, or a cut that takes longer to stop. This mainly becomes a concern at high vitamin E doses (around 800 IU or more daily), not the small amounts in food or a regular multivitamin. If you take high-dose vitamin E, just check with your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liede KE, Haukka JK, Saxen LM, Heinonen OP. Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med 1998;30:542-6.
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  3. Liu M, Wallmon A, Olsson-Mortlock C, et al. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr 2003;77:700-6. PubMed
  4. Schrogie JJ. Coagulopathy and fat-soluble vitamins (letter). JAMA 1975;232:19. DOI
  5. Celestini A, Pulcinelli FM, Pignatelli P, et al. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica 2002;87:420-6.
  6. Stampfer MJ, Jakubowski JA, Faigel D, et al. Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels. Am J Clin Nutr 1988;47:700-6. PubMed
  7. Jandak J, Steiner M, Richardson PD. Alpha-tocopherol, an effective inhibitor of platelet adhesion. Blood 1989;73:141-9. DOI
  8. Freedman JE, Farhat JH, Loscalzo J, Keaney JF. Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 1996;94:2434-40. PubMed
  9. Steiner M. Vitamin E, a modifier of platelet function: rationale and use in cardiovascular and cerebrovascular disease. Nutr Rev 1999;57:306-9. PubMed
  10. Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143-8. PubMed
  11. Abrol R, Kaushik R, Goel D, Sama S, Kaushik RM, Kala M. Vitamin E-induced coagulopathy in a young patient: a case report. J Med Case Rep 2023;17(1):107. 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

Vitamin E Also Interacts With Other Medications

Vitamin E has 762 moderate, 1 minor 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 762 Minor 1 No known interaction 2,067 (incl. Aspirin, Caffeine, Orphenadrine)
Taking anything else?

Check Another of Your Medications Against Vitamin E

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine

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

We hold 22,182 real supplement products containing Vitamin E, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Vitamin E. Your product may carry other ingredients that interact with Aspirin, Caffeine, Orphenadrine too, on top of Vitamin E — 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 Vitamin E 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 Vitamin E
Top 10

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

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Steady interest

#1,943 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 Vitamin E

What is Vitamin E?

Vitamin E
  • General antioxidant support
  • Skin and hair care
  • Heart health
  • Eye health (age-related conditions)
  • Immune support

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correct a true deficiency, but high-dose vitamin E has not been clearly proven to prevent heart disease or cancer and may carry risks. Talk to your pharmacist or doctor before taking high doses.

Read the full Vitamin E monograph & all interactions
Keep checking

Other Drugs & Vitamin E

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

0Major
762Moderate
1Minor
2,066No known interaction
762 Moderate 1 Minor 2,066 No interaction
Moderate

762 interactions

Showing 60 of 762 moderate interactions — see all 762 on the Vitamin E page.

Minor

1 interaction

No interaction 2,066 drugs checked — show the list

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

Showing the 60 most looked-up of 2,066 medications checked with no known interaction — see the full Vitamin E list.

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

Can you take Vitamin E 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 2 interactions listed for Vitamin E and Aspirin, Caffeine, Orphenadrine?
Aspirin, Caffeine, Orphenadrine belongs to more than one drug category, and Vitamin E 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 Vitamin E 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.