What are the side effects of Efudex (Fluorouracil)?

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Last updated: March 21, 2025View editorial policy

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From the Guidelines

Efudex (fluorouracil) cream commonly causes several side effects during treatment of precancerous skin lesions or skin cancers, including skin reactions at the application site such as redness, burning, pain, swelling, irritation, inflammation, and tenderness, as well as systemic effects like nausea, vomiting, diarrhea, and headaches if the medication is absorbed into the bloodstream 1.

Side Effects of Efudex (Fluorouracil)

The most frequent side effects of Efudex (fluorouracil) cream include:

  • Skin reactions at the application site such as redness, burning, pain, swelling, irritation, inflammation, and tenderness
  • Skin darkening or lightening
  • Scarring
  • Sensitivity to sunlight
  • Systemic effects like nausea, vomiting, diarrhea, and headaches if the medication is absorbed into the bloodstream As treatment progresses, the affected skin typically becomes crusty, develops erosions, and may ulcerate before healing 1.

Management of Side Effects

These reactions are expected and indicate the medication is working by destroying abnormal cells. Most side effects resolve within 1-2 months after completing treatment, though skin color changes may persist longer 1.

Patient Guidance

Patients should contact their healthcare provider if they experience severe pain, extensive ulceration, signs of infection, or any unexpected reactions during treatment. The use of 5-fluorouracil cream is recommended as a field treatment for actinic keratosis, with benefits assessed as moderate or large 1.

From the FDA Drug Label

ADVERSE REACTIONS: The most frequent adverse reactions to fluorouracil cream occur locally and are often related to an extension of the pharmacological activity of the drug. These include burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration Ulcerations, other local reactions, cases of miscarriage, and a birth defect (ventricular septal defect) have been reported when fluorouracil cream was applied to mucous membrane areas. Leukocytosis is the most frequent hematological side effect Although a causal relationship is remote, other adverse reactions which have been reported infrequently are: Central Nervous System:Emotional upset, insomnia, irritability. Gastrointestinal:Medicinal taste, stomatitis. Hematological:Eosinophilia, thrombocytopenia, toxic granulation Integumentary:Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash. Special Senses:Conjunctival reaction, corneal reaction, lacrimation, nasal irritation. Miscellaneous:Herpes simplex.

The side effects of Efudex (Fluorouracil) include:

  • Local reactions: burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration
  • Hematological side effects: leukocytosis, eosinophilia, thrombocytopenia, toxic granulation
  • Central Nervous System: emotional upset, insomnia, irritability
  • Gastrointestinal: medicinal taste, stomatitis
  • Integumentary: alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash
  • Special Senses: conjunctival reaction, corneal reaction, lacrimation, nasal irritation
  • Miscellaneous: herpes simplex 2

From the Research

Side Effects of Efudex (Fluorouracil)

  • The use of topical fluorouracil can cause considerable discomfort, including primary irritant dermatitis and allergic contact dermatitis, as noted in the study by 3.
  • Inflammation is a common side effect of topical fluorouracil treatment, and it is likely necessary for the therapeutic effect, as suggested by the study 4.
  • Other potential side effects of topical fluorouracil include:
    • Seborrheic dermatitis-like eruption at a distant site, as reported in the case study by 5.
    • Epidermal injury, inflammation, and extracellular matrix degradation, as observed in the molecular analysis by 6.
    • Redness, irritation, and burning sensations at the treatment site, although these specific side effects are not explicitly mentioned in the provided studies.
  • The frequency and severity of side effects may vary depending on the concentration and frequency of treatment, as well as individual patient factors, as discussed in the studies by 4 and 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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