Continuing Education Activity

Benzoyl peroxide is an over-the-counter topical medication and is also an FDA-approved prescription medication for the treatment of acne vulgaris. It is bactericidal with activity against Cutibacterium acnes on the skin and within the hair follicles. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, toxicology, and monitoring of the broad array of physiological possibilities when using benzoyl peroxide in the clinical setting.

Objectives:

• Identify the indications for benzoyl peroxide use.
• Summarize the mechanism of action of benzoyl peroxide.
• Describe the most common adverse effects associated with benzoyl peroxide use.
• Outline the importance of improving care coordination among the interprofessional team to improve outcomes for patients using benzoyl peroxide.

Indications

Benzoyl peroxide is an over-the-counter topical medication and is also an FDA-approved prescription medication for the treatment of acne vulgaris. It is bactericidal with activity against Cutibacterium acnes (C. acnes) on the skin and within the hair follicles. Benzoyl peroxide has mild sebostatic and keratolytic effects and is most effective when used combined with other acne vulgaris therapies.[1][2] In contrast to other topical antibiotics, drug resistance has not appeared to develop with benzoyl peroxide use.[1]

Off-label indications for benzoyl peroxide include[3][4][5][6][7]:

• Inflammatory forms of rosacea 
• Folliculitis including gram-negative folliculitis, non-infectious folliculitis, and drug-induced folliculitis (acneiform eruptions)
• Pseudo-folliculitis barbae
• Progressive macular hypomelanosis 
• Pressure ulcers
• Perforating diseases
• Pitted keratolysis

Mechanism of Action

Topical benzoyl peroxide exhibits bactericidal effects against Cutibacterium acnes, a key component of acne vulgaris.[1][2] Benzoyl peroxide, once absorbed by the skin, is converted to benzoic acid. Approximately 5% of the benzoic acid is systemically absorbed and excreted by the renal system. The remaining benzoic acid is metabolized by cysteine in the skin, releasing active free-radical oxygen species resulting in the oxidization of bacterial proteins.[8] Improvement of acne vulgaris occurs by reducing lipids, free fatty acids, and P. acnes.

After applying 10% benzoyl peroxide daily for two weeks, the amount of P. acnes in hair follicles decreased by 98%, and the amount of free fatty acids decreased by 50%, which is comparable to results obtained after four weeks of antibiotic therapy.[9] Topical benzoyl peroxide also has mild sebostatic effects contributing to its keratolytic activity and efficacy in treating comedonal acne.[1] Benzoyl peroxide effectively treats cutaneous ulcers through stimulation of healthy production of granulation tissue and rapid ingrowth of epithelium.[10] 

Administration

Benzoyl peroxide is available as both over-the-counter and prescription formulations in concentrations of 2.5%, 5%, and 10%. Available preparations include lotions, creams, gels, foams, solutions, cleansing bars, cleansing lotions, cloths, pads, masks, and shaving creams.  Each application vehicle has specific instructions for the frequency of use. Cleansing bars and washes are used one to three times a day, whereas mask application is a thin layer that is left on for 15 to 25 minutes once a week.[11] Studies have shown that to treat acne vulgaris, the combination products containing benzoyl peroxide and topical antibiotics or adapalene are more effective than either medication used alone.[12][13] Combination preparations with erythromycin or clindamycin are applied twice daily, whereas combination preparations with adapalene are applied once daily.[11]

Adverse Effects

The most common adverse effect from benzoyl peroxide is its bleaching quality, potentially causing the discoloration of colored fabrics and bleaching of hair.  At higher concentrations, topical benzoyl peroxide causes mild dryness, erythema, and scaling.[14] There are also case reports of contact dermatitis in a small percentage of patients, which should arouse suspicion in patients who develop marked erythema and irritation at the treatment site. In such instances, the prudent course of action is to discontinue the use of benzoyl peroxide.

Contraindications

Patients who present with a known history of hypersensitivity to benzoyl peroxide should not use benzoyl peroxide products. Patients with hypersensitivity to cinnamon and other benzoic acid derivatives should be cautious in using benzoyl peroxide as cross-reactivity may occur.[15]

Benzoyl peroxide is not indicated for use around the eyes, nose, mouth, mucous membranes, and open skin as it may cause severe irritation. In instances of mucous membrane or ocular contact, thoroughly rinse affected areas with water for a minimum of 15 minutes.

Patients should limit their UV exposure and apply sunscreen to decrease the risk of developing phototoxicity and skin irritation.[14] 

Children

There is little data available supporting the clinical safety and efficacy of benzoyl peroxide when used in children. Because of its minimal systemic absorption, topical benzoyl peroxide is generally regarded as being safe in the pediatric population.[16] 

Pregnancy

The FDA classifies benzoyl peroxide as pregnancy risk category C. The effects of benzoyl peroxide on reproductive health and fetal health are unknown. However, because of its minimal systemic absorption, topical application of benzoyl peroxide is generally considered safe during pregnancy.[17] 

Breast-feeding

There is not much data available on the use of benzoyl peroxide while breastfeeding. Because of its low rate of systemic absorption, minimal risk to the infant is likely, and the topical use of benzoyl peroxide is generally regarded as safe while breastfeeding, as long as its application is not where the infant would have direct contact during breastfeeding or close skin-on-skin contact.[17]

Drug Interactions

• Patients should avoid concomitant use of topical sulfone products (e.g., dapsone) with topical benzoyl peroxide as it reportedly causes yellowing of the skin and facial hair.[18] 
• Patients should avoid concomitant use of topical hydroquinone with topical benzoyl peroxide as it may result in increased skin irritation and transient staining of the epidermis.[19]
• Concomitant use of oral isotretinoin with topical benzoyl peroxide has been reported to result in increased skin irritation and dryness.[20] 
• Patients should avoid concurrent application of topical benzoyl peroxide with topical tretinoin as it results in decreased efficacy of tretinoin. Unlike tretinoin, adapalene is resistant to oxidation by benzoyl peroxide and is an acceptable combination product.[2]
• Concomitant use of topical anesthetics with topical benzoyl peroxide reportedly decreases the efficacy of anesthetics. For optimal results, the recommendation is to thoroughly wash the treatment area before applying topical anesthetics.[21]

Monitoring

There are no monitoring parameters identified for benzoyl peroxide, and no routine tests are recommended. Development of contact dermatitis to benzoyl peroxide should be monitored, with discontinuation of the medication in patients that develop marked erythema and irritation with its use. Before using benzoyl peroxide, a test area should have a test treatment to monitor for tolerability and sensitivity.[14][15]

Toxicity

Topical benzoyl peroxide is not to be taken by mouth; indications are strictly limited to topical use. In case of ingestion, patients should call 911, contact the poison control center (1-800-222-1222), or report to the nearest emergency department. There are no known antidotes for this medication.

Enhancing Healthcare Team Outcomes

The most common medications prescribed for acne vulgaris include benzoyl peroxide, retinoids, and topical/oral antibiotics. Despite their individual efficacy in treating mild-to-moderate acne vulgaris, studies have shown that the combined use of antibiotics or retinoids with benzoyl peroxide is more efficacious than either medication used alone. The combination is believed to be synergistic and has also been shown to prevent the development of antibiotic resistance.[2][12] However, in a survey of patients with an indication for benzoyl peroxide as an additional acne treatment, only 30% of the patients obtained the benzoyl peroxide product.[22] Therefore, to improve patient compliance and treatment efficacy, healthcare providers should seek to prescribe combination products that would result in simpler skincare regimens and greater patient adherence. The initial disadvantage of combination products is their increased cost and need to be refrigerated to prevent degradation.[11] Although refrigeration is encouraged, cost reduction is possible through the utilization of specialty compounding pharmacies.