Topical fluorouracil (5-FU) destroys AKs by blocking methylation of thymidylate synthetase, thereby interrupting DNA and RNA synthesis. This in turn prevents the proliferation of dysplastic cells in AK. Topical 5-FU is the most utilized treatment for AK, and often results in effective removal of the lesion. Overall, there is a 50% efficacy rate resulting in 100% clearance of AKs treated with topical 5-FU. 5-FU may be up to 90% effective in treating non-hyperkeratotic lesions. While topical 5-FU is a widely used and cost-effective treatment for AKs and is generally well tolerated, its potential side-effects can include: pain, crusting, redness, and local swelling. These adverse effects can be mitigated or minimized by reducing the frequency of application or taking breaks between uses. The most commonly used application regimen consists of applying a layer of topical cream to the lesion twice a day after washing; duration of treatment is typically 2–4 weeks to thinner skin like the cheeks and up to 8 weeks for the arms; treatment of up to 8 weeks has demonstrated a higher cure rate.