Continuing Education Activity

This activity explores benzoyl peroxide, an over-the-counter topical medication that is FDA-approved for addressing acne vulgaris. The educational content delves into its bactericidal properties, specifically targeting Cutibacterium acnes within the skin and hair follicles. This activity equips healthcare professionals with essential knowledge for effective utilization in clinical settings by focusing on indications, mechanisms of action, and safe administration practices. Critical components of this program include a thorough examination of adverse drug reactions, contraindications, drug-drug interactions, clinical toxicology, and the necessity of monitoring various physiological aspects during benzoyl peroxide use. The curriculum underscores the significance of understanding intricate pharmacology to enable tailored treatment plans aligned with individual patient needs. Prioritizing patient safety becomes paramount, particularly considering the distinctive characteristics of the targeted patient population.

Through an evidence-based approach, this educational initiative empowers healthcare professionals to make informed decisions, keeping them updated on the latest guidelines and recommendations and facilitating the optimal integration of benzoyl peroxide into treatment regimens, ultimately enhancing outcomes for patients grappling with acne vulgaris.

Objectives:

• Identify the indications for benzoyl peroxide use.
• Evaluate the mechanism of action of benzoyl peroxide.
• Identify the most common adverse effects associated with benzoyl peroxide use.
• Implement effective collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from benzoyl peroxide treatment.

Indications

Benzoyl peroxide is an over-the-counter (OTC) topical medication and an FDA-approved prescription medication for acne vulgaris. Benzoyl peroxide 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 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]

FDA-Approved Indications

Acne vulgaris

As per the latest guidelines from the American Academy of Dermatology (AAD) in 2024, benzoyl peroxide is recommended for treating patients with acne. Additionally, the AAD suggests using fixed-dose combinations, such as topical retinoids with benzoyl peroxide, and endorses benzoyl peroxide with topical retinoids and a topical antibiotic. The AAD also recommends incorporating systemic antibiotics with benzoyl peroxide and other topical therapies for acne management.[3]

Rosacea

The novel microencapsulated benzoyl peroxide 5% cream is a topical treatment option for moderate to severe papulopustular rosacea, effectively reducing papules, pustules, and telangiectasia.[4]

Off-Label Uses 

• 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 [5][6][7][8][9]

Mechanism of Action

Topical benzoyl peroxide demonstrates bactericidal effects against Cutibacterium acnes, a key component of acne vulgaris.[1][2] Following absorption through the skin, benzoyl peroxide undergoes conversion into benzoic acid. Around 5% of the benzoic acid is absorbed systemically and then excreted by the renal system. The remaining benzoic acid is metabolized by cysteine in the skin, releasing active free-radical oxygen species and oxidizing bacterial proteins.[10] Improvement of acne vulgaris occurs by reducing lipids, free fatty acids, and P. acnes.

After applying 10% benzoyl peroxide daily for 2 weeks, the amount of P. acnes in hair follicles decreased by 98%, and the amount of free fatty acids decreased by 50%, comparable to results obtained after 4 weeks of antibiotic therapy.[11] 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.[12]

Pharmacokinetics

Absorption: In vitro studies using excised human skin and in vivo studies on rhesus monkeys demonstrate that benzoyl peroxide penetrates the skin layers and is converted to benzoic acid. Using formulations containing lower concentrations of benzoyl peroxide (2.5%) can minimize skin irritation, improving tolerability and treatment outcomes.[13]

Distribution: The radiolabelled dose thoroughly penetrates the skin and recovers as benzoic acid. The dose in the skin is approximately half benzoic acid and half benzoyl peroxide.

Metabolism: The peroxide bond of benzoyl peroxide is cleaved to form 2 benzoyloxy radicals. Benzoic acid is a significant metabolite of benzoyl peroxide.

Elimination: Benzoic acid, the metabolite of benzoyl peroxide, is eliminated in the urine. Data regarding fecal elimination is not readily available.

Administration

Available Dosage Forms and Strengths

Benzoyl peroxide is commercially available in 2.5%, 5%, and 10% concentrations, both over-the-counter and prescription formulations. These products include lotions, creams, gels, foams, solutions, cleansing bars, lotions, cloths, pads, masks, and shaving creams. Benzoyl peroxide is also available in formulations such as benzoyl peroxide and clindamycin, benzoyl peroxide and erythromycin, benzoyl peroxide and adapalene, benzoyl peroxide and tretinoin, benzoyl peroxide and hydrocortisone, and benzoyl peroxide, clindamycin, and adapalene. Every vehicle application comes with instructions outlining the recommended frequency of use.

Adult Dosage

Cleansing bars and washes are used 1 to 3 times a day, whereas mask application is a thin layer left on for 15 to 25 minutes once a week.[14] Studies have shown that to treat acne vulgaris, the combination formulations containing benzoyl peroxide, adapalene, and topical antibiotics are more effective than either medication used alone.[15][16] Combination preparations with erythromycin or clindamycin are applied twice daily, whereas combination preparations with adapalene are applied once daily.[14]

Specific Patient Populations

Hepatic impairment: No dosage adjustments for hepatic impairment are specified in the product labeling for benzoyl peroxide.

Renal impairment: No dosage adjustments are provided for renal impairment in benzoyl peroxide's product labeling.

Pregnancy considerations: 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. Applying 5% benzoyl peroxide twice daily is considered a safe acne treatment throughout all stages of pregnancy. Despite limited research, its perceived low risk is attributed to minimal systemic absorption and quick renal excretion.[17][18]

Breastfeeding considerations: There is insufficient data on using 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 considered 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]

Pediatric patients: Little data supports benzoyl peroxide's clinical safety and efficacy when used in children. Because of its minimal systemic absorption, topical benzoyl peroxide is generally considered safe in the pediatric population.[19] 

Older patients: No dosage adjustments for older patients are provided in the product labeling.

Adverse Effects

The most common adverse effect of benzoyl peroxide is its bleaching quality, potentially causing the discoloration of colored fabrics and hair bleaching. At higher concentrations, topical benzoyl peroxide causes mild dryness, erythema, and scaling.[20] 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 stopping benzoyl peroxide.

Drug-Drug Interactions

• Patients should avoid concomitant use of topical sulfone products (eg, dapsone) with topical benzoyl peroxide as it reportedly causes skin and facial hair yellowing.[21] 
• 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.[22]
• Concomitant use of oral isotretinoin with topical benzoyl peroxide has been reported to result in increased skin irritation and dryness.[23] 
• Patients should avoid concurrent application of topical benzoyl peroxide with topical tretinoin as it decreases tretinoin's efficacy. 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.[24]

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 when using benzoyl peroxide, as cross-reactivity may occur.[25]

Warning and Precautions

Benzoyl peroxide is not indicated for use around the eyes, nose, mouth, mucous membranes, and open skin, as it may cause severe irritation. For mucous membrane or ocular contact, thoroughly rinse affected areas with water for a minimum of 15 minutes. Patients should minimize UV exposure and apply sunscreen to reduce the risk of developing phototoxicity and skin irritation.[20] 

Some formulations of benzoyl peroxide may include high concentrations of propylene glycol or dimethyl sulfoxide, both of which have been associated with an increased risk of adverse events.[26] Propylene glycol, when used in high doses or for prolonged periods, can lead to toxicity. Clinical features of propylene glycol toxicity in children may include seizures, central nervous system (CNS) toxicity, cardiac arrhythmia, hyperosmolarity, agitation, hemolysis, and lactic acidosis.[26][27]

Monitoring

No monitoring parameters were identified for benzoyl peroxide, and no routine tests are recommended. The development of contact dermatitis to benzoyl peroxide should be monitored, with discontinuation of the medication in patients who 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.[20][25]

Toxicity

Topical benzoyl peroxide should not 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 by clinicians include benzoyl peroxide, retinoids, and topical/oral antibiotics. Rosacea and refractory cases of acne vulgaris may require consultation with a dermatologist. Pharmacists should educate patients about adverse drug reactions. Nurses should explain the importance of compliance. Despite their efficacy in treating mild-to-moderate acne vulgaris, studies have shown that combining antibiotics or retinoids with benzoyl peroxide is more productive than using either medication alone. The combination is believed to be synergistic and has also been shown to prevent the development of antibiotic resistance.[2][15] 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.[28] 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.[14] Although refrigeration is encouraged, cost reduction is possible through the utilization of specialty compounding pharmacies. An interprofessional team approach between clinicians (MDs, DOs, NPs, PAs), pharmacists, dermatologists, and nurses is necessary to optimize patient outcomes with benzoyl peroxide.

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Kircik LH. The role of benzoyl peroxide in the new treatment paradigm for acne. J Drugs Dermatol. 2013 Jun 01;12(6):s73-6. [PubMed: 23839205]

2.

Zaenglein AL. Acne Vulgaris. N Engl J Med. 2018 Oct 04;379(14):1343-1352. [PubMed: 30281982]

3.

Reynolds RV, Yeung H, Cheng CE, Cook-Bolden F, Desai SR, Druby KM, Freeman EE, Keri JE, Stein Gold LF, Tan JKL, Tollefson MM, Weiss JS, Wu PA, Zaenglein AL, Han JM, Barbieri JS. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024 May;90(5):1006.e1-1006.e30. [PubMed: 38300170]

4.

Green LJ, Lain E, Prunty T, Rhoades R. Enhancing Topical Pharmacotherapy for Acne and Rosacea: Vehicle Choices and Outcomes. J Clin Aesthet Dermatol. 2022 May;15(5):36-40. [PMC free article: PMC9122274] [PubMed: 35642224]

5.

Leyden JJ. Topical treatment for the inflamed lesion in acne, rosacea, and pseudofolliculitis barbae. Cutis. 2004 Jun;73(6 Suppl):4-5. [PubMed: 15228127]

6.

Wu XG, Xu AE, Luo XY, Song XZ. A case of progressive macular hypomelanosis successfully treated with benzoyl peroxide plus narrow-band UVB. J Dermatolog Treat. 2010 Nov;21(6):367-8. [PubMed: 20524876]

7.

Fernández Vozmediano JM, Alonso Blasi N, Almenara Barrios J, Alonso Trujillo F, Lafuente L. [Benzoyl peroxide in the treatment of decubitus ulcers]. Med Cutan Ibero Lat Am. 1988;16(5):427-9. [PubMed: 3070200]

8.

Lukács J, Schliemann S, Elsner P. Treatment of acquired reactive perforating dermatosis - a systematic review. J Dtsch Dermatol Ges. 2018 Jul;16(7):825-842. [PubMed: 29927512]

9.

Vlahovic TC, Dunn SP, Kemp K. The use of a clindamycin 1%-benzoyl peroxide 5% topical gel in the treatment of pitted keratolysis: a novel therapy. Adv Skin Wound Care. 2009 Dec;22(12):564-6. [PubMed: 19935134]

10.

Nacht S, Yeung D, Beasley JN, Anjo MD, Maibach HI. Benzoyl peroxide: percutaneous penetration and metabolic disposition. J Am Acad Dermatol. 1981 Jan;4(1):31-7. [PubMed: 7204686]

11.

Nacht S, Gans EH, McGinley KJ, Kligman AM. Comparative activity of benzoyl peroxide and hexachlorophene. In vivo studies against propionibacterium acnes in humans. Arch Dermatol. 1983 Jul;119(7):577-9. [PubMed: 6222704]

12.

O'Meara SM, Cullum NA, Majid M, Sheldon TA. Systematic review of antimicrobial agents used for chronic wounds. Br J Surg. 2001 Jan;88(1):4-21. [PubMed: 11136304]

13.

Harper JC. Benzoyl peroxide development, pharmacology, formulation and clinical uses in topical fixed-combinations. J Drugs Dermatol. 2010 May;9(5):482-7. [PubMed: 20480791]

14.

Hoffman LK, Bhatia N, Zeichner J, Kircik LH. Topical Vehicle Formulations in the Treatment of Acne. J Drugs Dermatol. 2018 Jun 01;17(6):s6-s10. [PubMed: 29879262]

15.

Leyden JJ, Wortzman M, Baldwin EK. Antibiotic-resistant Propionibacterium acnes suppressed by a benzoyl peroxide cleanser 6%. Cutis. 2008 Dec;82(6):417-21. [PubMed: 19181031]

16.

Leyden JJ, Thiboutot D, Shalita A. Photographic review of results from a clinical study comparing benzoyl peroxide 5%/clindamycin 1% topical gel with vehicle in the treatment of rosacea. Cutis. 2004 Jun;73(6 Suppl):11-7. [PubMed: 15228129]

17.

Pugashetti R, Shinkai K. Treatment of acne vulgaris in pregnant patients. Dermatol Ther. 2013 Jul-Aug;26(4):302-11. [PubMed: 23914887]

18.

Ly S, Kamal K, Manjaly P, Barbieri JS, Mostaghimi A. Treatment of Acne Vulgaris During Pregnancy and Lactation: A Narrative Review. Dermatol Ther (Heidelb). 2023 Jan;13(1):115-130. [PMC free article: PMC9823189] [PubMed: 36447117]

19.

Coughlin CC, Swink SM, Horwinski J, Sfyroera G, Bugayev J, Grice EA, Yan AC. The preadolescent acne microbiome: A prospective, randomized, pilot study investigating characterization and effects of acne therapy. Pediatr Dermatol. 2017 Nov;34(6):661-664. [PubMed: 29024079]

20.

Foti C, Romita P, Borghi A, Angelini G, Bonamonte D, Corazza M. Contact dermatitis to topical acne drugs: a review of the literature. Dermatol Ther. 2015 Sep-Oct;28(5):323-9. [PubMed: 26302055]

21.

Dubina MI, Fleischer AB. Interaction of topical sulfacetamide and topical dapsone with benzoyl peroxide. Arch Dermatol. 2009 Sep;145(9):1027-9. [PubMed: 19770443]

22.

Saade DS, Maymone MBC, Secemsky EA, Kennedy KF, Vashi NA. Patterns of Over-the-counter Lightening Agent Use among Patients with Hyperpigmentation Disorders: A United States-based Cohort Study. J Clin Aesthet Dermatol. 2018 Jul;11(7):26-30. [PMC free article: PMC6057735] [PubMed: 30057662]

23.

Chernyshov PV, Tomas-Aragones L, Manolache L, Svensson A, Marron SE, Evers AWM, Bettoli V, Jemec GB, Szepietowski JC. Which acne treatment has the best influence on health-related quality of life? Literature review by the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes. J Eur Acad Dermatol Venereol. 2018 Sep;32(9):1410-1419. [PubMed: 29729107]

24.

Burkhart CG, Burkhart CN. Decreased efficacy of topical anesthetic creams in presence of benzoyl peroxide. Dermatol Surg. 2005 Nov;31(11 Pt 1):1479-80. [PubMed: 16416626]

25.

Shwereb C, Lowenstein EJ. Delayed type hypersensitivity to benzoyl peroxide. J Drugs Dermatol. 2004 Mar-Apr;3(2):197-9. [PubMed: 15098979]

26.

Benzoyl Peroxide Microsphere Formulations: What is the Science Supporting Microsphere Vehicle Technology and Clinical Use? J Clin Aesthet Dermatol. 2009 Sep;2(9):46-54. [PMC free article: PMC2923969] [PubMed: 20729960]

27.

Lim TY, Poole RL, Pageler NM. Propylene glycol toxicity in children. J Pediatr Pharmacol Ther. 2014 Oct-Dec;19(4):277-82. [PMC free article: PMC4341412] [PubMed: 25762872]

28.

Huyler AH, Zaenglein AL. Adherence to over-the-counter benzoyl peroxide in patients with acne. J Am Acad Dermatol. 2017 Oct;77(4):763-764. [PubMed: 28917458]

Disclosure: Taraneh Matin declares no relevant financial relationships with ineligible companies.

Disclosure: Preeti Patel declares no relevant financial relationships with ineligible companies.

Disclosure: Marcus Goodman declares no relevant financial relationships with ineligible companies.