There is evidence that the metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most marked on those cells which grow more rapidly and take up fluorouracil at a more rapid rate. The catabolic metabolism of fluorouracil results in degradation products (e.g., CO2, urea, α-fluoro-β-alanine) which are inactive. Systemic absorption studies of topically applied fluorouracil have been performed on patients with actinic keratoses using tracer amounts of 14C-labeled fluorouracil added to a 5% preparation. (See Full Prescribing Information.)

EFUDEX 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.

EFUDEX should be applied preferably with a nonmetal applicator or suitable glove. If EFUDEX is applied with the fingers, the hands should be washed immediately afterward. Actinic or Solar Keratosis: Apply cream or solution twice daily in an amount sufficient to cover the lesions. Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated. The usual duration of therapy is from 2 to 4 weeks. Complete healing of the lesions may not be evident for 1 to 2 months following cessation of EFUDEX therapy. Superficial Basal Cell Carcinomas: Only the 5% strength is recommended. Apply cream or solution twice daily in an amount sufficient to cover the lesions. Treatment should be continued for at least 3 to 6 weeks. Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated. (See Full Prescribing Information.)

The most frequent adverse reactions to EFUDEX 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 EFUDEX 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. (See Full Prescribing Information.)

EFUDEX may cause fetal harm when administered to a pregnant woman.

There is a possibility of increased absorption through ulcerated or inflamed skin.