INDICATIONS AND USAGE: Fluorouracil is recommended for the topical treatment of multiple actinic or solar keratoses.

In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites.

Safety and efficacy in other indications have not been established.

The diagnosis should be established prior to treatment, since this method has not been proven effective in other types of basal cell carcinomas.

With isolated, easily accessible basal cell carcinomas, surgery is preferred since success with such lesions is almost 100%.

The success rate with fluorouracil solution and a different dosage form is approximately 93%, based on 113 lesions in 54 patients.

Twenty-five lesions treated with the solution produced 1 failure and 88 lesions treated with a different dosage form produced 7 failures.

WARNINGS: Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.

Additionally, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when fluorouracil was applied to mucous membrane areas during pregnancy.

Occlusion of the skin with resultant hydration has been shown to increase percutaneous penetration of several topical preparations.

If any occlusive dressing is used in treatment of basal cell carcinoma, there may be an increase in the severity of inflammatory reactions in the adjacent normal skin.

A porous gauze dressing may be applied for cosmetic reasons without increase in reaction.

Exposure to ultraviolet rays should be minimized during and immediately following treatment with fluorouracil because the intensity of the reaction may be increased.

Patients should discontinue therapy with fluorouracil topical solution if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS ).

Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency.

One case of life-threatening systemic toxicity has been reported with the topical use of fluorouracil in a patient with DPD enzyme deficiency.

Symptoms included severe abdominal pain, bloody diarrhea, vomiting, fever, and chills.

Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the esophagus, stomach, and small bowel.

Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.

ADVERSE REACTIONS: The most frequent adverse reactions to fluorouracil 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 topical solution 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.

To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.