Folic Acid - Efudex (Fluorouracil) Interaction

Herbal: Folic Acid

Drug: Fluorouracil
Brand names: Efudex, Tolak

Medical Content Editor
Last updated Jun 22, 2025

Interaction Details

Fluorouracil is classified as belonging to the following category: 5-Fluorouracil

Theoretically, high doses of folic acid might increase the toxicity of 5-fluorouracil.
Increases in gastrointestinal side effects of 5-fluorouracil, such as stomatitis and diarrhea, have been described in two clinical studies when leucovorin, a form of folic acid, was administered with 5-fluorouracil.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Bedford Laboratories. Leucovorin calcium [package insert]. Bedford, OH. September 2008. Available at: http://www.bedfordlabs.com/BedfordLabsWeb/products/inserts/LCV-P02.pdf.

Folic Acid Overview

Folate and folic acid are forms of vitamin B9, essential for health. Folate occurs naturally in foods like leafy vegetables, legumes, and fruits, while folic acid is the synthetic form used in supplements and fortified foods. Since 1998, the US has fortified cereals, baking flour, pasta, and bakery items with folic acid to prevent deficiencies. Naturally occurring folate, or pteroylpolyglutamate, has lower bioavailability (40% to 50%) compared to nearly 100% for synthetic folic acid. Foods rich in folate include asparagus, mushrooms, yeast, legumes, spinach, broccoli, lettuce, bananas, melons, oranges, tomatoes, lemons, and animal products like beef liver and kidney. Some supplements contain L-5-methyltetrahydrofolate (L-5-MTHF), a reduced folate form. L-5-MTHF, dependent on vitamin B12 for metabolism, is absorbed faster and more effectively than folic acid, especially in individuals with specific MTHFR genotypes. Studies show that women taking L-5-MTHF had slightly higher red blood cell folate concentrations compared to those taking folic acid, although long-term use results in similar blood levels and effectiveness for preventing neural tube defects.
See More Information Regarding Folic Acid

Fluorouracil Overview

  • Fluorouracil is generally used in combination with other medications to treat colon cancer or rectal cancer (cancer that begins in the large intestine) that has gotten worse or spread to other parts of the body. Fluorouracil is used in combination with other medications to treat certain types of breast cancer after surgery to remove the tumor or radiation therapy. Fluorouracil is also used to treat cancer of the pancreas and stomach cancer. Fluorouracil is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in your body.

See More Information Regarding Fluorouracil Injection

Folic Acid - More Interactions

Folic Acid interacts with 40 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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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

Drug descriptions are provided by MedlinePlus.

Dr. Brian Staiger, PharmD

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Dr. Brian Staiger, PharmD

In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!

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