Vitamin E - Aspirin, Caffeine, Codeine Phosphate Interaction
Herbal: Vitamin E
Also Known As: Alpha-tocopherol, Beta-tocopherol, Delta-tocopherol, Gamma-tocopherol
Drug: Aspirin, Caffeine, Codeine Phosphate
Brand names:
Anacin w/ Codeine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 04, 2025
Interaction Details
Aspirin, Caffeine, Codeine Phosphate is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates
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.
Interaction Rating
Likelihood of Occurrence
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
References
- Landes N, Pfluger P, Kluth D, et al. Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol 2003;65:269-73. .
- Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737-40.
Interaction Details
Aspirin, Caffeine, Codeine Phosphate is classified as belonging to the following category: 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.
Interaction Rating
Likelihood of Occurrence
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
References
- 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.
- 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/.
- 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.
- Schrogie JJ. Coagulopathy and fat-soluble vitamins (letter). JAMA 1975;232:19.
- 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.
- 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.
- Jandak J, Steiner M, Richardson PD. Alpha-tocopherol, an effective inhibitor of platelet adhesion. Blood 1989;73:141-9.
- 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.
- Steiner M. Vitamin E, a modifier of platelet function: rationale and use in cardiovascular and cerebrovascular disease. Nutr Rev 1999;57:306-9.
- 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.
- 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.
Vitamin E Overview

Vitamin E - More Interactions
Vitamin E interacts with 742 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
Unknown | No interactions have been reported or no interaction data is currently available. |
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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.
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