Benzoyl peroxide has been one of the most important topical acne agents for a long time. It has a combination of antibacterial, anti-inflammatory and comedolytic properties. Benzoyl peroxide can penetrate through the follicular duct deeply into the infundibulum where it then releases oxygen to inactivate anaerobic bacteria that cannot live in its presence, P. acnes being one of those bacteria. A study by Bojar et al. (31) reported an almost 2-log10 decrease in the density of P acnes after two days of 5% benzoyl peroxide treatment. Pagnoni et al. (32) confirmed this rapid effect in their investigation that showed P. acnes count decreased by an average of 2-log after a three-day treatment with a 10% benzoyl peroxide cream, without any further decline by day 7. In contrast to the bacterial resistance known to be associated with the use of oral and topical antibiotics, the antibacterial activity of benzoyl peroxide occurs without the induction of bacterial resistance.
The anti-inflammatory effect of benzoyl peroxide is probably directly related to the decrease of P. acnes density in the sebaceous follicles. It is known that P. acnes induces monocytes to secrete pro-inflammatory cytokines such as tumour necrosis factor a (TNF-alpha), interleukin-1 b (IL-1b), and IL-8 through a Toll-like receptor 2-dependent pathway (33,34).
Benzoyl peroxide is commonly available as a liquid cleanser (2.5-10%), bar cleanser (5-10%), pads (3-9%), mask (2.5-5%), lotion (5-10%), cream (5-10%), and gel (2.5-20%). A report from the Global Alliance to Improve Outcomes in Acne (35) indicates that gel formulations may be more stable and may release benzoyl peroxide more consistently than creams and lotions.
Specific cleanser forms of benzoyl peroxide (5% and 10%) have been shown to reduce P. acnes density and inflammatory lesion counts. To increase the cleanser’s benefits, patients should be instructed to gently massage the cleanser into moistened skin and allow a 20-second contact time followed by a 10-second gentle rinse (36). Recently a benzoyl peroxide cleanser mask takes this one step further by allowing the patients to use the product either as a cleanser or as a mask that allows for even longer contact time (37).
Benzoyl peroxide can enhance the efficacy of concomitant antibiotic therapy and reduces the development of antibiotic-resistant P. acnes. When used in combination with oral antibiotics, it has been shown to reduce the resistance of bacteria to the systemic drug. Recently, new drugs have combined benzoyl peroxide with other topical antibiotics. These
formulations are available only by prescriptions and include erythromycin 3%-benzoyl peroxide 5% and clindamycin 1%—benzoyl peroxide 5% combinations. These products have been shown to have some additive effect compared to either drug alone and to reduce the resistance to the antibiotic.
Once absorbed by the skin, benzoyl peroxide is metabolized to benzoic acid and excreted in the urine as benzoate. There is no evidence of systemic toxicity caused by benzoyl peroxide in humans (38). Side effects of benzoyl peroxide may include mild to moderate irritation and skin dryness. Contact allergy has been reported in approximately 1% of patients. Additionally, benzoyl peroxide formulations may bleach fabrics and hair. It is the controversy over tumor-promoting reports from animal studies on benzoyl peroxide that caused the FDA to delay ruling on its monograph status. In the interim, the agency has issued proposed rules that recommend sun avoidance and the use of a sunscreen when using a benzoyl peroxide product to treat acne (39).
Many peer-reviewed studies have been published supporting the efficacy and safety of benzoyl peroxide in acne. This ingredient is the main OTC treatment suggested by dermatologists because of its undisputed efficacy in inflammatory lesions. In fact, a review of the literature by Eady et al. (40) showed that none of the topical antibiotics used in various studies was clinically better than benzoyl peroxide. A direct comparison between a 10% benzoyl peroxide gel, a 1% clindamycin lotion, and a 20% azelaic acid cream found that the 10% benzoyl peroxide gel was significantly superior in reducing P. acnes at two and four weeks of treatment (41). Clinically, benzoyl peroxide has also additive benefits when combined with other topical antibiotics (such as clindamycin or erythromycin) (42,43).
Several previous studies have originally documented the efficacy of 2.5-10% benzoyl peroxide, which were reported in the Advance Notice of Proposed Rulemaking for Topical OTC Acne Drugs and accepted as support for the efficacy of benzoyl peroxide in acne (44). It is interesting to note that higher concentrations of benzoyl peroxide have not been shown to be more effective in acne, but may actually increase the risk of irritation. An eight-week study (45) compared the efficacy of 2.5% benzoyl peroxide versus 10% benzoyl peroxide in 50 acne subjects. The results showed that both treatments significantly decreased the total number of papules and pustules, with no difference in effectiveness between the two concentrations. There was also basically no difference in the reduction of total lesions between the two concentrations, while the incidence and severity of adverse events was much higher in the 10% benzoyl peroxide group. Similar findings were reported by Mills et al. (46), in which they compared a 2.5% benzoyl peroxide against its vehicle, and against a 5% and a 10% benzoyl peroxide gel in three double-blind studies involving 153 patients with mild to moderately severe acne vulgaris. The 2.5% benzoyl peroxide formulation was more effective than its vehicle and equivalent to the 5% and 10% concentrations in reducing the number of inflammatory lesions.
Orth et al. (47) investigated the penetration of a 2.5% and a 10% benzoyl peroxide formulation into the sebaceous follicles using cyanoacrylate follicular biopsy. The results showed that benzoyl peroxide penetrated into the follicles within a few hours and that the 2.5% formulation delivered a similar amount of benzoyl peroxide as the 10% product. The authors suggested that the vehicle of the 2.5% formulation played a significant role in enhancing the delivery of benzoyl peroxide.
One of the few studies comparing benzoyl peroxide to topical retinoids was conducted by Belknap (48). He compared 5% benzoyl peroxide twice daily versus 0.05%
retinoic acid once daily in an eight-week study. Both treatments were “extremely effective” for all types of lesions and significantly reduced open and closed comedones after two weeks of treatment. Somewhat higher number of patients in the benzoyl peroxide group showed excellent results.
A study by Shalita et al. showed the additive effect of the cleanser in acne treatment (49). They compared the efficacy of a combination of benzoyl peroxide 6% cleanser and tretinoin 0.1% microsphere gel versus tretinoin alone during a 12-week study. Fifty-six subjects with moderate acne completed the study. Both treatments showed a significant reduction in inflammatory and non-inflammatory lesions from baseline. However, the combination regimen produced a greater reduction of inflammatory acne lesions than the monotherapy without increasing local irritation.
Recently, a British study compared the efficacy and treatment costs of benzoyl peroxide versus oral antibiotics (50). This 18-week study evaluated five antimicrobial acne treatments in approximately 650 participants: oral oxytetracycline; oral minocycline; benzoyl peroxide; separate administration of topical erythromycin and benzoyl peroxide; and a combination of topical erythromycin and benzoyl peroxide. The authors found that topical 5% benzoyl peroxide used twice daily as single active agent was similar in efficacy to 100 mg minocycline once daily. The analysis of cost-effectiveness found that the cheapest treatment (benzoyl peroxide) was 12 times more cost-effective than minocycline. Additionally, the authors noted that pre-existing propionibacterial resistance compromised the clinical efficacy of oral tetracyclines. In contrast, regimens combining benzoyl peroxide with erythromycin were unaffected by resistance. The authors concluded that topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral antibiotics (oxytetracycline and minocycline). The more significant message is that the clinical equivalence comes without being affected by propionibacterial antibiotic resistance.