5-Fluorouracil (5-FU): 4% vs 5% for the Treatment of Actinic Keratosis


While oxymetazoline HCl cream, 1% and bromocriptine gel, 0.33% were not compared in a head-to-head trial, this has been done for 4% 5-FU in an aqueous vehicle cream containing peanut oil (Tolak) vs 5% 5-FU in a vanishing cream (Efudex) in patients with actinic keratosis (AKs).

In a 4-week, double-blind, multicenter non-inferiority study that included 841 subjects, 4% 5-FU cream administered once daily was compared with 5% 5-FU cream twice daily with 100% and 75% clinical clearance of AK’s assessed as the study endpoint.

4% 5-FU achieved 100% clearance in 80% of patients and 75% clearance in 100% of patients compared with 75% and 95%, respectively, with 5% 5-FU.

Skin irritation occurred in 30% of patients treated with 4% 5-FU vs 60% with 5% 5-FU.

It was also noted that the peanut oil component of the 4% 5-FU preparation is safe even in peanut-allergic patients.

Thus, 4% 5-FU is non-inferior to 5% 5-FU with better tolerability and permits once-daily administration which may result in better adherence to therapy (Dohil, 2016).


Dohil MA. Efficacy, safety, and tolerability of 4% 5-fluorouracil cream in a novel patented aqueous cream containing peanut oil once daily compared with 5% 5-fluorouracil cream twice daily: meeting the challenge in the treatment of actinic keratosis. J Drugs Dermatol. 2016;15:1218-1224.