Benzoyl Peroxide

(USAN)
Benzoyl Peroxide Chemical formula
Synonyms: Bensoylperoxid; Bentsoyyliperoksidi; Benzoilo peroksidas; Benzoil-peroxid; Benzoyil Peroksit; Benzoylis peroxidum; Benzoylperoxid; NSC-675; Peróxido de benzoilo; Peroxyde de benzoyle. Dibenzoyl peroxide.
Cyrillic synonym: Бензоил Пероксид; Пероксид Бензоила.

💊 Chemical information

Chemical formula: C14H10O4 = 242.2.
CAS — 94-36-0 (anhydrous benzoyl peroxide).
ATC — D10AE01.
ATC Vet — QD10AE01; QD11AX90.

Pharmacopoeias.

In Chin., Eur., Int., and US.

Ph. Eur. 6.2

(Benzoyl Peroxide, Hydrous). It contains not less than 70% and not more than 77% of anhydrous benzoyl peroxide and not less than 20% of water. It rapidly loses water on exposure to air and may explode if the water content is too low. A white or almost white, amorphous or granular powder. Practically insoluble in water; slightly soluble in alcohol; soluble in acetone; soluble in dichloromethane with separation of water. Store at 2° to 8° in a container that has been treated to reduce static charges and that has a device for the release of excess pressure. Unused material should not be returned to its original container but should be destroyed by the addition of sodium hydroxide solution (10%). Destruction can be considered to be complete if the addition of a crystal of potassium iodide does not result in the release of free iodine after acidification with dilute hydrochloric acid. Protect from light.

USP 31

(Hydrous Benzoyl Peroxide). It contains not less than 65% and not more than 82% of anhydrous benzoyl peroxide with a water content of about 26%. The hydrous form is a white granular powder with a characteristic odour. Sparingly soluble in water and in alcohol; soluble in acetone, in chloroform, and in ether. Store in the original container, treated to reduce static charges. Unused material should not be returned to its original container but should be destroyed by the addition of sodium hydroxide solution (10%). Destruction can be considered to be complete if the addition of a crystal of potassium iodide does not result in the release of free iodine.

💊 Adverse Effects and Precautions

Topical application of benzoyl peroxide may produce skin irritation, particularly at the start of treatment. In some patients the irritation may require reduced frequency of application or temporary suspension of treatment. Skin dryness, peeling, rash, and transient local oedema may also occur. Contact sensitisation has been reported in some patients using preparations containing benzoyl peroxide. Caution is required when applying it near the eyes, the mouth and other mucous membranes, and to the neck and other sensitive areas. Patients should be alerted to benzoyl peroxide’s bleaching property.

Body odour.

An unusual unpleasant body odour in a patient was attributed to the topical use of benzoyl peroxide.1
1. Molberg P. Body odor from topical benzoyl peroxide. N Engl J Med 1981; 304: 1366.

Carcinogenicity.

There has been concern at the implications of some animal studies showing benzoyl peroxide to possess some tumour-promoting activity.1 However, a retrospective survey in Canada concluded that there was no indication that the normal use of benzoyl peroxide in the treatment of acne was associated with an increased risk of facial cancer.2 A comprehensive review3 that included in-vitro and animal studies, as well as human data, also concluded that there was no evidence to associate the topical use of benzoyl peroxide with the development of skin cancer in humans. However, the International Agency for Research on Cancer4 considers that there is inadequate evidence in humans and its overall evaluation is that benzoyl peroxide is not classifiable as to its carcinogenicity to humans.
1. Jones GRN. Skin cancer: risk to individuals using the tumour promoter benzoyl peroxide for acne treatment. Hum Toxicol 1985; 4: 75–8
2. Hogan DJ, et al. A study of acne treatments as risk factors for skin cancer of the head and neck. Br J Dermatol 1991; 125: 343–8
3. Kraus AL, et al. Benzoyl peroxide: an integrated human safety assessment for carcinogenicity. Regul Toxicol Pharmacol 1995; 21: 87–107
4. IARC/WHO. Benzoyl peroxide. IARC monographs on the evaluation of carcinogenic risks to humans volume 71 1999. Available at: http://monographs.iarc.fr/ENG/Monographs/vol71/ volume71.pdf (accessed 27/09/07)

Handling.

Benzoyl peroxide powder may explode if subjected to grinding, percussion, or heat. Hydrous benzoyl peroxide containing water to reduce the risk of explosion may still explode if exposed to temperatures higher than 60° or cause fires in the presence of reducing substances.

Hypersensitivity.

Benzoyl peroxide appears to induce contact hypersensitivity quite often when used to treat leg ulcers,1 but it is unclear how often this occurs when used in the treatment of acne.2 Patch testing3,4 in some studies suggests that up to 76% of patients may be hypersensitive to benzoyl peroxide but this does not appear to correlate either with the clinical irritation produced during treatment, which usually resolves on continued use, or with the reported incidence of hypersensitivity.2,4 In one study 25% of patients were considered to be hypersensitive from patch testing but only 2 of 44 patients developed clinical hypersensitivity.4 Another study involving 204 patients with acne found that the incidence of false-positive irritant skin reactions to benzoyl peroxide was about 15% but only 1% of the patients had true allergic reactions to the drug on further testing.5 However, there has been concern that hypersensitivity to benzoyl peroxide may be mistaken for irritation or worsening of the acne.3
1. Vena GA, et al. Contact dermatitis to benzoyl peroxide. Contact Dermatitis 1982; 8: 338
2. Cunliffe WJ, Burke B. Benzoyl peroxide: lack of sensitization. Acta Derm Venereol (Stockh) 1982; 62: 458–9
3. Leyden JJ, Kligman AM. Contact sensitization to benzoyl peroxide. Contact Dermatitis 1977; 3: 273–5
4. Rietschel RL, Duncan SH. Benzoyl peroxide reactions in an acne study group. Contact Dermatitis 1982; 8: 323–6
5. Balato N, et al. Acne and allergic contact dermatitis. Contact Dermatitis 1996; 34: 68–9.

💊 Pharmacokinetics

1. Yeung D, et al. Benzoyl peroxide: percutaneous penetration and metabolic disposition II: effect of concentration. J Am Acad Dermatol 1983; 9: 920–4.

💊 Uses and Administration

Benzoyl peroxide has mild keratolytic properties. Its antimicrobial action is probably due to its oxidising effect and activity has been reported against Staphylococcus epidermidis and Propionibacterium acnes. It is used mainly in the treatment of acne (below), applied once or twice daily in topical preparations usually containing 2.5 to 10%, sometimes with other antimicrobials. For use in young children, see below. It has been used similarly in the treatment of fungal skin infections, such as tinea pedis although other drugs are usually preferred. A 20% lotion has been applied every 8 to 12 hours in the treatment of decubitus or stasis ulcers. Strengths are expressed as anhydrous benzoyl peroxide although it is used in a hydrous form for safety (see Pharmacopoeias, above). Benzoyl peroxide is also used as a bleaching agent in the food industry and as a catalyst in the plastics industry.

Acne.

Benzoyl peroxide applied topically in concentrations of up to 10% is probably the most widely used first-line drug in the management of mild acne. Early studies in animals found benzoyl peroxide to be sebosuppressive1 but later studies demonstrated that sebum excretion rises during the first few months of treatment,2,3 probably due to the comedolytic action of benzoyl peroxide, and remains at a stable level thereafter. Benzoyl peroxide has been shown to have a significant inhibitory effect on skin microflora, with reductions in surface and follicular micro-organisms within 48 hours of beginning treatment, but clinical improvement took several more days to appear.4 The combined use of benzoyl peroxide with topical clindamycin or erythromycin can inhibit the development of antibacterial resistance and bring about clinical improvement when resistance already exists.5
1. Gloor M, et al. Cytokinetic studies on the sebo-suppressive effect of drugs using the example of benzoyl peroxide. Arch Dermatol Res 1980; 267: 97–9
2. Cunliffe WJ, et al. Topical benzoyl peroxide increases the sebum excretion rate in patients with acne. Br J Dermatol 1983; 109: 577–9
3. Pierard-Franchimont C, et al. Topical benzoyl peroxide increases the sebum excretion rate. Br J Dermatol 1984; 110: 506
4. Bojar RA, et al. The short-term treatment of acne vulgaris with benzoyl peroxide: effects on the surface and follicular cutaneous microflora. Br J Dermatol 1995; 132: 204–8
5. Taylor GA, Shalita AR. Benzoyl peroxide-based combination therapies for acne vulgaris: a comparative review. Am J Clin Dermatol 2004; 5: 261–5.

Administration in children.

Benzoyl peroxide has been used topically in the treatment of neonatal and infantile acne, applied once or twice daily starting with lower strength preparations of 2.5%.

💊 Preparations

BP 2008: Benzoyl Peroxide Cream; Benzoyl Peroxide Gel; Benzoyl Peroxide Lotion; Potassium Hydroxyquinoline Sulphate and Benzoyl Peroxide Cream; USP 31: Benzoyl Peroxide Gel; Benzoyl Peroxide Lotion; Erythromycin and Benzoyl Peroxide Topical Gel.

Proprietary Preparations

Arg.: Acnepas; Acnesan; Benzihex; Clidan B; Eclaran; Ecnagel PB; Paracne; PB Gel; Solugel; Tiltis; Vixiderm E; Austral.: Benzac; Brevoxyl; Clearasil Ultra; Neutrogena Acne Mask†; Oxy; PanOxyl; Austria: Akneroxid; Benzaknen; Brevoxyl; PanOxyl; Scherogel; Belg.: Akneroxid; Benzac; Brevoxyl; Pangel; Braz.: Acnase; Benzac AC; PanOxyl; Solugel; Canad.: Acetoxyl; Benoxyl; Benzac; Benzagel†; Clean & Clear Continuous Control; Clean & Clear Persa Gel; Clearasil B.P. Plus; Dermance†; Dermoxyl†; Desquam-X; Neo Strata Astringent Acne Treatment†; Neo Strata Blemish Spot†; Neutrogena Acne Mask†; Neutrogena On The Spot Acne Treatment†; Oxy; Oxyderm; PanOxyl; Solugel; Chile: Benzac; Pansulfox; Peroxiben Plus; Pirobac; Solugel; Cz.: Aknecide†; Aknefug-oxid†; Akneroxid; Antopar†; Basiron AC; Eclaran; Inoxitan†; Oxy; Fin.: Basiron; Brevoxyl; Fr.: Brevoxyl; Cutacnyl; Eclaran; Effacne; Pannogel; PanOxyl; Ger.: Aknederm Oxid†; Aknefug-oxid; Akneroxid; Benzaknen; Benzoyt; Benzperox; Brevoxyl; Cordes BPO; Dercome; Klinoxid; Marduk; PanOxyl; Sanoxit; Scherogel†; Gr.: Benzac-W; Brevoxyl; Hong Kong: Acnacyl†; Acneclear; Benzac AC; Brevoxyl; Oxy; PanOxyl; Hung.: Acne-Med†; Aknefug-oxid; Akneroxid; Lubexyl; India: Benzac AC; Persol; Indon.: Benzolac; Pimplex; Irl.: Acnecide; Brevoxyl; PanOxyl; Israel: Acne Derm; Acne Mask†; Benzac AC; Clearex Cover Up; Oxy; Oxy Sensitive; PanOxyl; Ital.: Benoxid; Benzac; PanOxyl; Reloxyl; Malaysia: Akneroxid; Benzac AC; Brevoxyl; PanOxyl; Mex.: Akeprul; Benoxyl; Benzac AC; Benzaderm; Oxy†; Solugel; Neth.: Akneroxid; Benzac; Clearamed†; Oxy; Tendox; Norw.: Basiron; Brevoxyl; PanOxyl; NZ: Benzac; Brevoxyl; Clearasil Ultra; PanOxyl; Philipp.: Benoxyl; Benzac AC; Brevoxyl; PanOxyl; Ultra Clearasil; Pol.: Akneroxid; Benzacne; Benzapur; Brevoxyl; Clearasil Ultra†; Lubexyl; Port.: Benacne; Benoxygel; Benzac; Eclaran; Lutsimed; PanOxyl; Peroxiben; Rus.: Basiron (Базирон); S.Afr.: Benoxyl; Benzac AC; Brevoxyl; Clearasil Benzoyl P; Dry & Clear; PanOxyl; Singapore: Acnacyl†; Akneroxid; Benzac; Brevoxyl; PanOxyl; Spain: Benoxygel; Oxiderma; PanOxyl; Peroxacne; Peroxiben; Solucel; Stop Espinilla Normaderm; Swed.: Basiron; Bexid†; Brevoxyl; Stioxyl†; Switz.: Acnefuge†; Akneroxid; Aknex; Basiron†; Benzac; Effacne†; Lubexyl; PanOxyl†; Thai.: Acnexyl†; Benzac; Brevoxyl; PanOxyl; Turk.: Aknefug BP; Aksil; Benzac AC; UK: Acnecide; Brevoxyl; Oxy; PanOxyl; USA: Acne Clear; Ambi 10; Benzac; Benziq; Brevoxyl; Clearasil; Clinac BPO; Del Aqua; Desquam; Fostex; NeoBenz; Oxy; PanOxyl; Triaz; Zaclir; Venez.: Acnex; Benoxyl†; Benzac AC; Ecuaderm; PanOxyl†; Solugel†. Multi-ingredient: Arg.: Acnepas E; Benzamycin†; Clindacur; Clindoxyl; CP-Acne; Dermaclean; Duo Clindacin; Erimicin; Kitacne PB†; Pentoclave Combi; Perclin; Peroximicina; Austral.: Duac; Austria: Acne Plus; Clindoxyl; Belg.: Acneplus; Benzamycin; Braz.: Acnase; Akirol†; Benzac Eritromicina†; Clindoxyl; Canad.: Benzaclin; Benzamycin; Clindoxyl; Chile: Benzac Plus; Benzamycin†; Erimicin; Indoxyl; Klina; Cz.: Duac; Fr.: Epiduo; Ger.: Acne Plus; Gr.: Benzamycin†; Indoxyl; Hong Kong: Benzamycin; Duac; India: Persol For te; Indon.: Benzolac Cl; Feldixid; Irl.: Benzamycin; Duac; Quinoderm; Israel: Benzamycin; Ital.: Acnidazil; Delta 80; Delta 80 Plus; Katoxyn; Mex.: Benzac Plus; Benzaclin; Benzamycin; Clindapack; Indoxyl; Neth.: Acnecare; Acnecure†; Acnidazil†; Duac; NZ: Duac; Philipp.: Acne Plus; Pol.: Duac; Port.: Duac; Zacne; S.Afr.: Acneclear; Acnidazil; Benzamycine†; Quinoderm; Singapore: Benzamycin; Spain: Duac; Swed.: Duac; Switz.: Acne Creme Plus; Turk.: Benzamycin; UK: Benzamycin†; Duac Once Daily; Quinoderm; USA: Benzaclin; Benzamycin; Duac; Sulfoxyl; Vanoxide-HC; Zacare Kit; Zoderm.
Published November 13, 2018.