ATC Class:D01AE12

VA Class:DE500

AHFS Class:

• Keratolytic Agents 84:28

Generic Name(s):

• Salicylic Acid

Salicylic acid is a keratolytic agent.

Salicylic acid is used topically for its keratolytic effect in the management of acne and other skin conditions such as seborrheic dermatitis, psoriasis, and dandruff; the drug also is used topically for the removal of warts, corns, and calluses.100,  101,  102,  103,  109,  117,  118,  122,  123

Salicylic acid is not used systemically because of its severe irritating effect on GI mucosa and other tissues. (See the Salicylates General Statement 28:08.04.24.)

Acne

Salicylic acid is used topically for the management of acne.100,  104,  105,  113,  114,  115 The drug is commercially available in a variety of nonprescription (over-the-counter, OTC) preparations for the management of acne; for self-medication , topical preparations containing salicylic acid 0.5-2% are used.100,  118

Although clinical studies evaluating the efficacy of topical salicylic acid for the treatment of acne are limited, the drug has been shown to reduce the formation of comedones.118,  119,  125,  126 However, some experts state that salicylic acid generally is less effective than other topical acne treatments, particularly benzoyl peroxide.119

Seborrheic Dermatitis, Psoriasis, and Dandruff

Salicylic acid is used topically for its keratolytic effect in controlling seborrheic dermatitis of the body and scalp, psoriasis of the body and scalp, and dandruff.103,  109,  121 For self-medication of these conditions, topical preparations containing salicylic acid 1.8-3% are used.103

When used for the topical treatment of psoriasis, salicylic acid reduces scaling and thickness of the skin, and softens psoriatic plaques.121,  127 However, clinical studies evaluating the efficacy of topical salicylic acid as a single-agent therapy are limited; in a few controlled studies, salicylic acid was not more effective than placebo in the treatment of scalp psoriasis.121,  127 Improvements in efficacy may be achieved when salicylic acid is used in combination with other topical therapies, presumably due to increased skin penetration of other active ingredients as a result of the keratolytic effects of salicylic acid.127

Hyperkeratosis

Salicylic acid is used topically for its keratolytic effect in the removal of common and plantar warts, corns, and calluses.101,  102,  106,  107,  110,  111,  112,  116,  122,  123 For self-medication of common or plantar warts, topical preparations containing salicylic acid 12-40% (in plaster), 5-17% (in a collodion-like vehicle), or 15% (in a karaya gum-glycol plaster vehicle) are used.101 For self-medication of corns and calluses, topical preparations containing salicylic acid 12-40% (in plaster) or 12-17.6% (in a collodion-like vehicle) are used.102 The fixed-combination preparation containing salicylic acid 5% and urea 10% (Kerasal^® Foot Ointment) is used to soften and control the growth of calluses.108 Salicylic acid also is available as a 6% cream or lotion (Salex^®) for the topical treatment of hyperkeratotic skin disorders including verrucae, ichthyoses vulgaris, palmoplantar keratosis, keratosis pilaris, pityriasis rubra pilaris, and psoriasis (including body, scalp, palms, and soles).117

Salicylic acid is considered first-line therapy for the topical treatment of common and plantar warts.123 Compared with placebo, the drug has demonstrated modest benefits in the treatment of cutaneous warts; however, several weeks of therapy may be required to obtain a therapeutic effect.122

Administration

Salicylic acid is applied topically to the skin as a cake, cream, gel, lotion, ointment, pledget, plaster, shampoo, solution, or suspension.104,  105,  106,  107,  108,  109,  110,  111,  112,  113,  114,  115,  116,  117 Topical preparations of salicylic acid are for external use only.100,  101,  102,  103 Contact with the eyes should be avoided; if contact occurs, the affected eye(s) should be washed thoroughly with water.101,  102,  103

Prior to topical application, the affected area(s) to be treated should be cleansed and allowed to dry.100,  101,  102,  104 Prior to removal of warts, corns, and calluses, the affected area may be soaked in warm water for 5 minutes.101,  102

Salicylic acid is commercially available in various preparations, some of which are intended for self-medication ; the manufacturer's product labeling should be consulted for complete directions regarding appropriate dosage and administration of specific products.100,  101,  102,  103

Dosage

Acne

For self-medication of acne, a thin layer of an appropriate preparation containing salicylic acid 0.5-2% should be applied topically to the affected area 1-3 times daily.100,  104,  105,  113,  114,  115 Salicylic acid preparations that are intended to be applied and removed such as a cleanser, soap, mask, or scrub should be rinsed thoroughly from the application site with water.100,  104,  105 If a salicylic acid solution-containing pledget is used, a single pad should be used to wipe the entire affected area; a second, clean pad may be used if necessary to remove remaining traces of dirt.113

To avoid excessive drying, therapy generally is initiated with a single application daily; the frequency is then increased gradually to 2-3 times daily as necessary or directed by a clinician.100,  104,  113,  114 If bothersome dryness or peeling occurs, the frequency of applications should be reduced to once daily or every other day.100,  104,  105,  113,  114

Seborrheic Dermatitis, Psoriasis, and Dandruff

For self-medication of seborrheic dermatitis, psoriasis, or dandruff, an appropriate preparation containing salicylic acid 1.8-3% should be applied topically to the affected area of the skin and/or scalp.103,  109 Salicylic acid preparations that are intended to be left on the skin or scalp (e.g., creams, ointments, lotions) should be applied 1-4 times daily to the affected areas or as directed by a clinician.103 Preparations that are intended for use as a soap or shampoo should be applied to affected areas in place of regular soap or shampoo.103,  109 Preparations used as a shampoo should be applied to wet skin or scalp and washed off after several minutes, and repeated if necessary.103,  109

Wart Removal

For self-medication of common or plantar warts, an appropriate preparation containing salicylic acid 12-40% (in plaster), 5-17% (in a collodion-like vehicle), or 15% (in a karaya gum-glycol plaster vehicle) should be applied topically to the affected area.101 If a plaster preparation is used, the plaster should be trimmed (if necessary) to fit over the wart and applied; the plaster should be removed after 48 hours.101,  112 This process should be repeated every 48 hours as needed for up to 12 weeks until the wart is removed.101,  112

If a salicylic acid preparation in a collodion-like vehicle is used, a small amount (e.g., one drop at a time) should be applied with an applicator to sufficiently cover the wart and allowed to dry.101,  107,  111

If a salicylic acid preparation in a karaya gum-glycol plaster vehicle is used, the wart surface should be gently smoothed with an emery board prior to application.101 A drop of warm water should be applied to the wart, keeping the surrounding area dry.101 The plaster should be trimmed (if necessary), applied at bedtime, and left in place for at least 8 hours; the plaster should be removed the following morning.101 This process should be repeated every 24 hours as needed for up to 12 weeks until the wart is removed.101

If a salicylic acid 27.5 or 28.5% solution (e.g., UltraSal^®-ER, Virasal^®) is used, the wart should be soaked in warm water for 5 minutes prior to application.106,  116 Any loose tissue should be removed by gently rubbing the skin (e.g., with a wash cloth, emery board, or brush); the site should be dried thoroughly.106,  116 The salicylic acid solution should be applied twice to the affected area (while avoiding surrounding normal skin) using the brush applicator supplied by the manufacturer, allowing the first application to dry before applying the second.106,  116 Treatment should be continued once or twice daily as directed by the clinician.106,  116 Clinical improvement usually is evident during the first or second week of therapy, with full resolution after 4-6 weeks; however, some warts may take longer to remove.106,  116

Corn and Callus Removal

For self-medication of corns and calluses, an appropriate preparation containing salicylic acid 12-40% (in plaster) or 12-17.6% (in a collodion-like vehicle) should be applied topically to the affected area.102 If a plaster preparation is used, the plaster should be trimmed (if necessary) to fit over the callus or corn and then applied; the plaster should be removed after 48 hours.102,  112 This process should be repeated every 48 hours as needed for up to 14 days until the corn or callus is removed.102,  112

If a salicylic acid preparation in a flexible collodion-like vehicle is used, a small amount (e.g., one drop at a time) should be applied with an applicator to sufficiently cover each corn or callus and allowed to dry.102,  110 The process should be repeated once or twice daily as needed for up to 14 days until the corn or callus is removed.102,  110

When the fixed-combination preparation containing salicylic acid 5% and urea 10% (Kerasal^® Foot Ointment) is used to soften and control the growth of calluses, a small amount should be applied daily and gently massaged into the affected skin until fully absorbed.108 For faster results, the product should be applied in the evening and occluded with cotton socks.108

Other Hyperkeratotic Skin Disorders

If salicylic acid 6% cream or lotion is used for the removal of excessive keratin in hyperkeratotic skin disorders, including verrucae, ichthyoses vulgaris, palmoplantar keratosis, keratosis pilaris, pityriasis rubra pilaris, or psoriasis (including body, scalp, palms, and soles), the preparation should be applied topically to the affected area(s) at bedtime and covered with an occlusive dressing.117 The affected areas of skin should be hydrated (e.g., with wet packs or baths) for at least 5 minutes prior to application.117 The drug should be washed off in the morning; if the affected skin is irritated or excessively dry, a bland cream or lotion may be applied.117 If occlusion is not possible, the preparation can be applied more frequently; however, excessive, repeated application does not necessarily increase therapeutic benefit and may increase the risk of adverse local effects and salicylism.117 (See Cautions.)

Adverse Effects

Local dermatologic effects such as skin peeling, discomfort, irritation, and dryness may occur following topical application of salicylic acid; risk of such reactions is increased at concentrations of 2% or greater and with concomitant use of other topical acne medications.104,  105,  106,  113,  114,  116,  118,  124

Because salicylic acid is rapidly and efficiently absorbed percutaneously following topical application to the skin, adverse effects as a result of systemic exposure to the drug are possible.118,  120 Possible systemic effects include salicylate toxicity, toxic inner ear damage, and hypersensitivity.118,  120 Acute salicylate intoxication has been reported with the use of topical salicylate products following treatment for psoriasis, dermatitis, and other skin conditions; in all cases, salicylic acid was applied to a large body surface area.118,  120 The use of topical acne products containing salicylic acid has not been associated with systemic toxicity.118

Precautions and Contraindications

Topical preparations containing salicylic acid are intended for external use only.100,  101,  102,  103 If contact with the eye(s) occurs, the affected eye(s) should be rinsed thoroughly with water.101,  102,  103 If topical salicylic acid-containing preparations are used for self-medication and the condition worsens or does not improve after regular use as directed, a clinician should be consulted.103,  109

Rare, but serious hypersensitivity reactions have occurred with certain nonprescription (over-the-counter, OTC) topical acne preparations containing salicylic acid or benzoyl peroxide.124 At least 131 such cases were reported to the FDA between 1969 and 2013, with the majority of cases reported since 2012.124 Manifestations occurred within minutes to 24 hours of product use, and ranged from local site reactions (e.g., skin irritation, burning, erythema, dermatitis) to anaphylactic reactions requiring hospitalization.124 Although resolution occurred to some degree following product discontinuance, hypersensitivity recurred in some patients following rechallenge.124 It is not clear whether the reported cases of hypersensitivity were triggered by benzoyl peroxide, salicylic acid, or an inactive ingredient contained in the preparation.124 Patients should immediately discontinue use of any topical acne preparation if they experience symptoms of a serious hypersensitivity reaction (e.g., hives, itching, throat tightness, difficulty breathing, faintness, swelling of the eyes, face, lips, or tongue), and should avoid future use of the product.124 To reduce the risk of serious hypersensitivity reactions, FDA recommends sensitivity testing (e.g., application of a small amount for 3 days) prior to first use of a topical acne preparation.124

Although systemic effects are minimal when salicylic acid is applied topically to intact skin in low to moderate dosages, salicylate toxicity (e.g., nausea, vomiting, dizziness, loss of hearing, tinnitus, lethargy, hyperpnea, diarrhea, psychosis) is possible after prolonged or excessive use of topical salicylic acid preparations.117,  118,  120 Topical preparations containing salicylic acid should not be used for self-medication of large areas of the body.103,  109 Concomitant use of oral aspirin and other salicylate-containing products (e.g., salicylate athletic creams) should be avoided in patients receiving topical salicylic acid preparations to minimize exposure to salicylic acid.117 If salicylate toxicity occurs, the salicylic acid preparation should be immediately discontinued, and the appropriate treatment instituted (e.g., fluids to promote urinary excretion; oral or IV sodium bicarbonate).117

When used for self-medication of acne, topical salicylic acid-containing preparations generally should not be used concurrently with other topical acne medications because of the increased risk of skin dryness and irritation.100,  104 Salicylic acid wart, corn, and callus removal preparations should not be used in patients with diabetes mellitus or with poor blood circulation.101,  107

Possible local irritation may occur if topical salicylic acid preparations used for the removal of warts are applied to normal skin; care should be taken during administration to avoid contact with normal skin surrounding the wart.106,  116 If excessive irritation occurs, treatment should be discontinued.106,  116 Possible excessive erythema or scaling may occur if salicylic acid preparations are applied to open skin lesions.117

Because salicylic acid is rapidly and efficiently absorbed percutaneously following topical application to the skin, drug interactions as a result of systemic exposure to the drug are possible.118 (See Drug Interactions in the Salicylates General Statement 28:08.04.24.)

Some manufacturers state that use of salicylic acid is contraindicated in patients known to be sensitive to the drug or any other ingredient contained in the product.117 Manufacturers of some salicylic acid wart removal preparations state that the drug is contraindicated in patients with diabetes or impaired blood circulation; the drug also is contraindicated for use on moles, birthmarks, and unusual warts with hair growing from them, or warts on the face.106,  116

Pediatric Precautions

Because of a greater risk of systemic absorption and toxicity, some experts recommend that topical salicylic acid be avoided in children.127 Some manufacturers state that use of salicylic acid is contraindicated in pediatric patients under 2 years of age.117

Manufacturers of some topical salicylic acid preparations for the treatment of psoriasis or seborrheic dermatitis state that the drug is intended for self-medication in normal healthy adults only; pediatric patients younger than 18 years of age should use only under the direction of a clinician.109

Salicylates should not be used in children and adolescents with varicella infection or influenza because of an increased risk of developing Reye's syndrome.117

Pregnancy and Lactation

Pregnancy

There are no adequate and well-controlled studies of topical salicylic acid in pregnant women; the drug should be used during pregnancy only if the potential benefits justify the possible risks to the fetus.117

Lactation

Because of the potential for serious adverse reactions to salicylic acid in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.117 If used in nursing women, the drug should not be applied to the chest area to avoid accidental contamination of the infant.117

Pharmacology

Salicylic acid has a potent keratolytic action and a slight antiseptic action when applied topically to the skin. Although the exact mechanism of action is not known,106,  116 salicylic acid produces desquamation of the horny layer (stratum corneum) of the skin by dissolving the intercellular cement that holds epithelial cells together.117,  118,  120 In the treatment of warts, the keratolytic activity of salicylic acid may result in the mechanical removal of epidermal cells infected with wart viruses.106,  116 In low concentrations, the drug has keratoplastic activity (correction of abnormal keratinization) and in higher concentrations (i.e., 1% or higher, depending on the vehicle), the drug has keratolytic activity (causes peeling of skin). Salicylic acid softens and destroys the stratum corneum by increasing endogenous hydration (water concentration), probably because of decreased pH, which causes the cornified epithelium (horny layer) of the skin to swell, soften, and then desquamate. Necrosis of normal skin has been associated with overuse of the drug. At high concentrations (e.g., 20%), salicylic acid has a caustic effect. The drug also has weak antifungal and antibacterial activity.

Chemistry and Stability

Chemistry

Salicylic acid is a keratolytic agent. Salicylic acid occurs as white crystals, usually in fine needles, or as a fluffy, white, crystalline powder. The drug has a sweetish taste and an acrid aftertaste and is slightly soluble in water and freely soluble in alcohol. Salicylic acid has pK_as of 2.97 and 13.4. The drug is found principally in wintergreen leaves and in the bark of sweet birch, but can be prepared synthetically.

Stability

Salicylic acid should be stored at room temperature in well-closed containers;106,  116,  117 freezing should be avoided.117 Preparations of salicylic acid in flexible collodion are flammable and should not be stored near heat or an open flame.101,  102,  107,  110,  111

100. Department of Health and Human Services, Food and Drug Administration. Part 333---Topical antimicrobial drug products for over-the-counter human use. Subpart D---Topical acne drug products. (21 CFR Ch. 1 (Current as of 10-30-15.)) 2015. From Electronic Code of Federal Regulations website. [Web]

101. Department of Health and Human Services, Food and Drug Administration. Part 358---Miscellaneous external drug products for over-the-counter human use. Subpart B---Wart remover drug products. (21 CFR Ch. 1 (Current as of 10-30-15.)) 2015. From Electronic Code of Federal Regulations website. [Web]

102. Department of Health and Human Services, Food and Drug Administration. Part 358---Miscellaneous external drug products for over-the-counter human use. Subpart F---Corn and callus remover drug products. (21 CFR Ch. 1 Current as of 10-30-15.)) 2015. [Web]

103. Department of Health and Human Services, Food and Drug Administration. Part 358---Miscellaneous external drug products for over-the-counter human use. Subpart H---Drug products for the control of dandruff, seborrheic dermatitis, and psoriasis. (21 CFR Ch. 1 (Current as of 10-30-15.)) 2015. [Web]

104. Unilever. Noxzema^® Ultimate Clear Anti-Blemish Daily Scrub (salicylic acid 1%) product information. Trumbull, CT. 2012 Oct.

105. Rodan and Fields. Proactiv^® cleaning bar (salicylic acid 1%) product information. San Francisco, CA. 2010 Sep.

106. Elorac. UltraSal-ER^® (28.5% Salicylic Acid Extended Release) antiviral film-forming solution) prescribing information. Vernon Hills, IL; 2014 Jan.

107. Prestige. Compound W^® Fast Acting Wart Removal Gel (salicylic acid 17%) product information. Tarrytown, NY. Undated.

108. Moberg Pharma. Kerasal^®Exfoliating Moisturizer Foot Therapy (salicylic acid 5% and urea 10%) product information. Undated.

109. Alva-Amco Pharmacal. Psoriasin^® Therapeutic Shampoo and Body Wash (salicylic acid 3%) product information. Niles, IL. 2010 May.

110. Pedinol Pharmacal. Hydrisalic^® gel (salicylic acid 17%) product information. Farmingdale, NY; 2014 Nov.

111. Prestige. Compound W^® Fast Acting Liquid (salicylic acid 17%) product information. Tarrytown, NY. Undated.

112. Medline Industries. Mediplast^® Corn, Callus, and Wart Remover (salicylic acid 40% ) plaster product information. Mundelein, IL. 2012 Nov.

113. Blistex. Stridex^® Essential (salicylic acid 1%) pads product information. Oak Brook, IL. 2013 Dec.

114. Neutrogena Coporation. Neutrogena Rapid Clear^® Acne Eliminating Spot Gel (salicylic acid 2%) product information. Los Angeles, CA. 2015 May.

115. Rodan and Fields. Proactiv^® Advanced Daily Oil Control (salicylic acid 0.5%) product information. San Francisco, CA. 2012 Aug.

116. Elorac. Virasal^® (salicylic acid 27.5%) antiviral film-forming vehicle product information. Vernon Hills, IL. 2011 Jan.

117. Coria Laboratories. Salex^® (salicylic acid 6%) cream and lotion prescribing information. Fort Worth, TX; 2013 July.

118. Akhavan A, Bershad S. Topical acne drugs: review of clinical properties, systemic exposure, and safety. Am J Clin Dermatol . 2003; 4:473-92. [PubMed 12814337]

119. Eichenfield LF, Krakowski AC, Piggott C et al. Evidence-based recommendations for the diagnosis and treatment of pediatric acne. Pediatrics . 2013; 131 Suppl 3:S163-86. [PubMed 23637225]

120. Madan RK, Levitt J. A review of toxicity from topical salicylic acid preparations. J Am Acad Dermatol . 2014; 70:788-92. [PubMed 24472429]

121. Mason AR, Mason J, Cork M et al. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev . 2013; 3:CD005028. [PubMedCentral][PubMed 23641480]

122. Kwok CS, Gibbs S, Bennett C et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev . 2012; 9:CD001781.

123. Dall'oglio F, D'Amico V, Nasca MR et al. Treatment of cutaneous warts: an evidence-based review. Am J Clin Dermatol . 2012; 13:73-96. [PubMed 22292461]

124. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns of rare but serious hypersensitivity reactions with certain over-the-counter topical acne products. Rockville, MD; 2014 Jun 25. From FDA website. Accessed 2015 Jul 30. [Web]

125. Titus S, Hodge J. Diagnosis and treatment of acne. Am Fam Physician . 2012; 86:734-40. [PubMed 23062156]

126. Shalita AR. Comparison of a salicylic acid cleanser and a benzoyl peroxide wash in the treatment of acne vulgaris. Clin Ther . 1989 Mar-Apr; 11:264-7.

127. Menter A, Korman NJ, Elmets CA et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol . 2009; 60:643-59. [PubMed 19217694]