Products
5-Fluorouracil is commercially available as an ointment (Efudix), as a topical solution in combination with salicylic acid (Verrumal), and in preparations for parenteral administration. This article refers to topical application. In 2011, 5-fluorouracil at the lower concentration of 0.5% was approved in many countries with Actikerall.
Structure and properties
5-Fluorouracil (C4H3FN2O2, Mr = 130.08 g/mol) is a uracil fluorinated in the 5-position, analogous to thymine (5-methyluracil). Together with the bases cytosine and thymidine, uracil belongs to the so-called pyrimidine analogs. It is incorporated into RNA as a false building block.5-Fluorouracil exists as a white to almost white crystalline powder that is sparingly soluble in water.
Effects
5-Fluorouracil (ATC L01BC02, ATC D11AF) has cytostatic effects by inhibiting DNA and RNA synthesis. It also stops the growth and multiplication of wart viruses. Salicylic acid is keratolytic and improves the penetration of fluorouracil into tissues.
Mechanism of action
The cytostatic effect of 5-fluorouracil is due to inhibition of thymidylate synthetase, which is responsible for methylation of dUMP. The result is the blockage of DNA synthesis. The incorporation of 5-fluorouracil into RNA and the resulting reduced incorporation of uracil lead to the inhibition of RNA synthesis. The result is inhibition of cell proliferation in rapidly dividing dysplastic cells, leading to cell death.
Indications
Locally, 5-fluorouracil is used for actinic keratosis, basal cell carcinoma, squamous cell carcinoma, premalignant changes, and Bowen’s disease. In combination with salicylic acid, it is also approved for the treatment of warts, particularly plantar and vulgar warts. Other off-label indications are described in the literature.
Dosage
According to the drug label. Care should be taken during application because 5-fluorouracil should not come into contact with intact skin, mucous membranes, or eyes. Therefore, it is recommended to wash hands well after application or to wear protective gloves during application.
Contraindications
5-Fluorouracil is contraindicated in hypersensitivity, concomitant use of antiviral nucleosides, and during pregnancy. For complete precautions, see the Drug Information Sheet.
Interactions
5-Fluorouracil is degraded by the enzyme dihydropyrimidine dehydrogenase. Therefore, it should not be taken concomitantly with the nucleoside analogues brivudine and sorivudine. This could lead to an increase in the plasma concentration of fluorouracil and concomitant increase in toxicity.
Adverse effects
Possible adverse effects include sometimes severe inflammatory reactions, allergic skin reactions such as redness of healthy skin, burning sensation, a skin inflammation, and itching. Side effects most commonly occur at the site of application.