VA Class:DE200

ATC Class:D07AB08

AHFS Class:

• Corticosteroids 84:06.08

Associated Monographs

• Alclometasone

• Amcinonide

• Betamethasone

• Clobetasol

• Clocortolone

• Desonide

• Desoximetasone

• Diflorasone

• Fluocinolone

• Flurandrenolide

• Halcinonide

• Hydrocortisone

• Mometasone

• Prednicarbate

• Triamcinolone

Hydrocortisone or synthetic derivatives of hydrocortisone are used topically as anti-inflammatory agents.

Dermatoses

Topical corticosteroids are used for the symptomatic relief of inflammatory dermatoses. The cause of the dermatoses should be determined and eliminated if possible; dermatoses are controlled but not cured by these drugs. Although systemic corticosteroids are more effective in most dermatologic inflammations, topical treatment is preferred in most responsive cases because it causes fewer adverse systemic effects.

Topical corticosteroids generally are most effective in the treatment of acute or chronic dermatoses such as seborrheic or atopic dermatitis, localized neurodermatitis, anogenital pruritus, psoriasis, and the inflammatory phase of xerosis. Topical corticosteroids are effective in the late phase of allergic contact dermatitis or irritant dermatitis, but systemic corticosteroids are usually required to relieve the acute manifestations of these dermatoses.

Individual topical corticosteroid preparations vary in anti-inflammatory activity (as measured by vasoconstrictor assay) and in percutaneous penetration, but therapeutic efficacy of a particular drug can often be increased by increasing the concentration or by using occlusive dressing therapy. As with systemic use, some patients may respond better to one topical corticosteroid than to another. Topical corticosteroid preparations may be grouped according to relative anti-inflammatory activity, but activity may vary considerably depending upon the vehicle, the site of application, disease, the individual patient, and whether or not an occlusive dressing is used. (See Pharmacokinetics.) Approximate relative activity (based principally on vasoconstrictor assay and/or clinical effectiveness in psoriasis) of some topical corticosteroid preparations in decreasing order is as follows (preparations in each group are approximately equivalent):

Although some dermatoses may require therapy with a relatively more active corticosteroid initially, treatment with hydrocortisone, dexamethasone (a topical preparation is no longer commercially available in the US) , methylprednisolone, or prednisolone, which are generally considered to be less active (i.e., Group VII) than preparations in groups I-VI, is often sufficient and is less likely to cause adverse reactions. Although fluorinated corticosteroids are generally more biologically active and have greater antimitotic activity than nonfluorinated drugs, fluorination is not essential for increased anti-inflammatory activity (e.g., hydrocortisone valerate has more topical anti-inflammatory activity than does betamethasone or dexamethasone). Relatively more active corticosteroids with or without occlusive dressing therapy are used for severe or resistant dermatoses such as psoriasis and chronic neurodermatitis. Dermatoses such as discoid lupus erythematosus, lichen planus, granuloma annulare, and psoriasis of palms, soles, elbows, and knees or psoriatic plaques usually require topical corticosteroids with increased anti-inflammatory activity and occlusive dressings or intralesional or sublesional corticosteroid injections. Hypertrophic lichen planus, alopecia areata, hypertrophic scars, and keloids generally require intralesional corticosteroid therapy.

Ulcerative Colitis and Anorectal Disorders

Hydrocortisone is used as a retention enema in the adjunctive treatment of mild or moderate acute ulcerative colitis limited to the rectosigmoid or left colon and, to a lesser extent, in some patients with mild acute ulcerative colitis of the transverse or descending colon. Corticosteroid enemas are usually effective in patients with mild or moderate acute ulcerative colitis of the rectosigmoid who do not adequately respond to sulfasalazine alone or in whom sulfasalazine cannot be given; sulfasalazine is generally considered the drug of choice for maintenance therapy in mild or moderate ulcerative colitis. Systemic corticosteroids and/or corticosteroid enemas are more effective than sulfasalazine in acute attacks of ulcerative colitis but, if surgery is required, it should not be delayed in favor of corticosteroid therapy.

Hydrocortisone acetate, as rectal suppositories or a suspension (foam), may be effective in the adjunctive treatment of ulcerative colitis of the rectum. As rectal suppositories, hydrocortisone acetate is also used in the treatment of other inflammatory conditions of the anorectum (e.g., inflamed hemorrhoids, postirradiation or factitial proctitis, cryptitis, pruritus ani).

Preparations containing a corticosteroid and local anesthetic may be useful in the symptomatic relief of anorectal disorders such as hemorrhoids, but commercially available corticosteroid combinations with antihistamines, astringents, keratolytics, and/or vasoconstrictors are of questionable efficacy.

Other Uses

Topical corticosteroids are commercially available in combination with antibiotics such as neomycin and antifungals such as clioquinol (iodochlorhydroxyquin). Results of some well-controlled clinical studies using cortisol suggest that these combination preparations are more effective than either the corticosteroid or anti-infective agent alone in infected dermatoses. Combined therapy with triamcinolone and nystatin has been shown to be more effective than nystatin alone for improving the clinical severity of cutaneous candidiasis, especially during the first few days of therapy;205 combined therapy generally provides earlier relief of signs and symptoms of this infection than does nystatin alone.204,205 If topical corticosteroids are used in combination with topical anti-infective agents, the benefit must be weighed against the risk of contact sensitization to the anti-infective agent and suppression by the corticosteroid of manifestations of infection. (See Cautions: Precautions and Contraindications.)

For EENT uses of corticosteroids, see 52:08. For systemic and intralesional uses of corticosteroids, see 68:04.

For dermatologic use, topical corticosteroids are available in various dosage forms including creams, dressings (tape), foams, gels, lotions, ointments, solutions, and aerosols (suspensions). The choice of a dosage form depends on the location of the lesion and the condition being treated. Lotions are probably best for the treatment of weeping eruptions, especially in areas subject to chafing such as the axilla, foot, and groin. Lotions, gels, and aerosols may be used on hairy areas, particularly the scalp. Creams are suitable for most dermatoses, but ointments, which may also provide some occlusion, are usually used for the treatment of dry, scaly lesions. Because certain areas of the body may be more susceptible to atrophic changes than others following treatment with corticosteroids,215,221 certain topical corticosteroid preparations (e.g., betamethasone dipropionate 0.05% gel; clobetasol propionate 0.05% cream, foam, gel, lotion, solution, or shampoo; hydrocortisone valerate 0.2% cream; mometasone furoate 0.1% cream, lotion, or ointment) should not be applied to the face or intertriginous areas (e.g., axilla, groin).207,212,213,214,215,216,217,218,219,220,221

Because the formulation of dermatologic corticosteroid products affects percutaneous penetration and subsequent activity of the drug, extemporaneous preparation or dilution of most commercially available products with another vehicle may result in decreased effectiveness.

The area of skin to be treated may be thoroughly cleansed before topical application of corticosteroids to reduce the risk of infection. However, some clinicians believe that, unless an occlusive dressing is used, cleansing of the treated area is unnecessary and may be irritating. Topical corticosteroids are generally applied sparingly in thin films and rubbed gently into the affected area 1-4 times daily. When a favorable response is achieved, the frequency of application or concentration of the corticosteroid is reduced to the minimum necessary to maintain control and avoid relapse and, if possible, the drug should be discontinued.

For occlusive dressing therapy, the affected area is soaked or washed to remove scales and a corticosteroid cream, lotion, or ointment is applied in a thin film or is rubbed gently into the lesion and another thin film applied. After applying the corticosteroid, the affected area is covered with a thin, pliable plastic film which is sealed to adjacent normal skin with adhesive tape or held in place by a gauze or elastic bandage. If the affected area is moist, the edges of the plastic film may be incompletely sealed or the film may be punctured to allow excess moisture to escape. For added moisture in dry lesions, the corticosteroid may be covered with a dampened cloth before the plastic film is applied or the affected area may be briefly soaked in water before application of the drug and plastic film. Thin polyethylene gloves may be used on the hands and fingers, plastic garment bags may be used on the trunk or buttocks, a tight shower cap may be used for the scalp, or whole-body suits may be used instead of plastic film to provide occlusion. Flurandrenolide tape may be used alone as an occlusive dressing for small areas.

The frequency of occlusive dressing changes depends on the condition being treated; cleansing of the skin and reapplication of the corticosteroid are essential at each dressing change. The occlusive dressing is usually left in place for 12-24 hours and therapy is repeated as needed. Some manufacturers state that the occlusive dressing may be left in place for 3-4 days at a time in resistant conditions, because theoretically the longer the occlusive dressing is left in place at one time, the more rapidly the dermatoses respond to topical corticosteroid therapy. However, most clinicians recommend intermittent use of occlusive dressings for 12 hours daily to reduce the risk of adverse effects (particularly infection) and systemic absorption and for greater convenience. For example, the corticosteroid and an occlusive dressing may be used at night, and the topical corticosteroid or a bland emollient may be used without an occlusive dressing during the day. In patients with extensive lesions, sequential occlusion of only one portion of the body at a time may be preferable to whole-body occlusion.

Systemic Effects

In general, topical application of corticosteroids to the skin does not provoke clinical evidence of systemic absorption. However, adverse systemic corticosteroid effects may occur when the drugs are used on large areas of the body, for prolonged periods of time, with an occlusive dressing, and/or in infants and children or when potent agents (e.g., those in group I) are used. (See Cautions: Precautions and Contraindications.) Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria have occurred in some patients receiving topical corticosteroids. Recovery of HPA-axis function is generally prompt and complete following discontinuance of the drug. In some patients, signs and symptoms of steroid withdrawal may occur, necessitating supplemental systemic corticosteroid therapy. Reversible HPA-axis suppression has occurred following topical dosages as low as 2 g of the 0.05% clobetasol propionate cream or ointment (1 mg of the drug) daily or 7 g of the 0.05% betamethasone dipropionate cream in an optimized vehicle (3.5 mg of betamethasone) daily or following repeated application of 14 g of the 0.05% betamethasone dipropionate ointment in an optimized vehicle (7 mg of betamethasone) daily in patients with psoriasis. Numbness of fingers has been reported in patients receiving topical clobetasol propionate preparations. In at least one patient receiving hydrocortisone buteprate cream, paresthesia has been reported.

Rectal administration or topical application of corticosteroids to the genitourinary tract for prolonged periods produces systemic effects. For cautions in the systemic use of corticosteroids, see the Corticosteroids General Statement 68:04.

Local Effects

Topical corticosteroids may cause adverse dermatologic effects. Adverse dermatologic effects are most likely to occur in intertriginous and facial areas and are most severe with fluorinated corticosteroids; fluorinated derivatives should be used with caution on the face. Local adverse corticosteroid effects occur most frequently with occlusive dressings, especially with prolonged therapy, and may require discontinuing the occlusive dressing.

Topical corticosteroids may cause atrophy of the epidermis, subcutaneous tissue, and dermal collagen and drying and cracking or tightening of the skin. Epidermal thinning, telangiectasia, increased fragility of cutaneous blood vessels, purpura, and atrophic striae may also occur. Other adverse dermatologic effects of topical corticosteroids include acne, acneiform eruption, vesiculation, irritation, pruritus, hypertrichosis, rosacea-like eruptions on the face, erythema, hyperesthesia, urticaria, perioral dermatitis, burning or stinging sensation, folliculitis, hypopigmentation, and alopecia. Skin ulceration has occurred in patients with impaired circulation who were treated with topical corticosteroids. Local pain or burning and rectal bleeding have occurred rarely with rectal administration of hydrocortisone as an enema.

Adverse dermatologic effects of topical corticosteroids usually improve when the drug is discontinued but may persist for long periods; atrophic striae may be permanent. When prolonged (2 months or more) topical fluorinated corticosteroid therapy is discontinued, pustular “rebound” may occur, especially on the face, perianal region, or genitals. Although improvement usually occurs spontaneously within a few weeks, some patients may require treatment with a systemic antibiotic (e.g., tetracycline) and a topical nonfluorinated corticosteroid (e.g., hydrocortisone) and/or sulfur.

In addition to the other adverse dermatologic effects of topical corticosteroid therapy, maceration of the skin and miliaria may occur, especially when occlusive dressings are used. Stripping of the epidermis and purpura have occurred with flurandrenolide tape dressings.

Topically applied corticosteroids are generally nonsensitizing, but allergic contact dermatitis may occur rarely. Allergic contact dermatitis associated with topical corticosteroids usually is diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical preparations that do not contain corticosteroids; such an observation should be corroborated with appropriate diagnostic patch testing.

Dermatologic infection may occur with topical corticosteroid therapy, particularly when an occlusive dressing is used. The anti-inflammatory activity of the drugs can also mask the manifestations of infection.

Precautions and Contraindications

Patients receiving large doses of a potent topical corticosteroid applied to extensive areas or under an occlusive dressing should be evaluated periodically for evidence of HPA-axis suppression by using the urinary free cortisol test, plasma cortisol test, or corticotropin (ACTH) stimulation test. If HPA-axis suppression is evident, an attempt should be made to withdraw the drug, reduce the frequency of application, or substitute a less potent topical corticosteroid.

Patients receiving topical corticosteroids should be instructed to use the preparations only as directed by the physician, only for the disorder for which it was prescribed, and for no longer than the time period prescribed. Unless occlusive dressings are part of the prescribed regimen, patients should be instructed that treated areas of skin should not be bandaged or otherwise covered or wrapped as to be occlusive. Occlusive dressings (including flurandrenolide tape) should not be used on weeping or exudative lesions, and flurandrenolide tape should not be used in intertriginous areas. Because thermal homeostasis may be impaired when occlusive dressings cover large areas, they should be removed if body temperature increases. Care should be taken to avoid the risk of suffocation with the plastic occlusive material. Some potent topical corticosteroids (e.g., betamethasone dipropionate, clobetasol propionate) should not be used with occlusive dressings because of the risk of adverse systemic effects. (See Dosage and Administration in the individual monographs in 84:06.08.)

Because certain areas of the body may be more susceptible to atrophic changes than others following treatment with corticosteroids,215,221 certain topical corticosteroid preparations (e.g., betamethasone dipropionate 0.05% gel; clobetasol propionate 0.05% cream, foam, gel, lotion, solution, or shampoo; hydrocortisone valerate 0.2% cream; mometasone furoate 0.1% cream, lotion, or ointment) should not be applied to the face or intertriginous areas (e.g., axilla, groin).207,212,213,214,215,216,217,218,219,220,221

Patients should be carefully monitored when topical corticosteroids are used in the treatment of psoriasis, because exacerbation of the disease or development of pustular psoriasis may occur during topical corticosteroid therapy or when the drugs are withdrawn.

Some commercially available formulations of topical corticosteroids contain sulfites that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

If skin irritation or contact dermatitis occurs during topical corticosteroid therapy, the drug should be discontinued and appropriate therapy initiated. It should be kept in mind that occlusive plastic dressings rarely may cause local or hypersensitivity reactions.

Topical corticosteroids should not be used in patients with markedly impaired circulation since skin ulceration has occurred in these patients following use of the drugs.

Topical corticosteroids should be used with caution and occlusive dressings should not be used in patients with primary skin infection. If secondary infection of the inflammatory lesion(s) develops, the occlusive dressing should be discontinued and appropriate topical anti-infective therapy initiated. If the infection does not respond promptly to such therapy, the manufacturers recommend that corticosteroid therapy be discontinued until the infection has been controlled. Some manufacturers state that topical corticosteroids are contraindicated in patients with tuberculosis of the skin, dermatologic fungal infections, and cutaneous or systemic viral infection, including vaccinia and varicella and herpes simplex of the eye or adjacent skin. However, most clinicians believe topical corticosteroids can be used with caution if the infection is treated. Corticosteroids reportedly may produce false-negative results with the nitroblue-tetrazolium test for bacterial infections.

The immunosuppressive effects of corticosteroids may be associated with impairment of the normal function of T cells and macrophages; such impairment may result in activation of latent infection or exacerbation of intercurrent infections, including those caused by Candida , Mycobacterium , Toxoplasma , Strongyloides , Pneumocystis , Cryptococcus , Nocardia , and ameba. Corticosteroid-containing preparations should be used with caution in patients with impaired T-cell function or in those receiving other immunosuppressive therapy.

Ocular instillation should be avoided when topical corticosteroids are applied on the eyelids or skin near the eyes because of the risk of corticosteroid-induced open-angle glaucoma.

Rectal corticosteroid therapy should be used with caution in patients with severe ulcerative disease, and only after adequate proctologic examination, because of the risk of intestinal perforation. Rectal corticosteroid therapy is contraindicated in patients with intestinal obstruction, abscess, impending perforation, peritonitis, extensive fistulas, and fresh intestinal anastomoses or sinus tracts.

Topical corticosteroid therapy is contraindicated in patients hypersensitive to any component of the preparation.

Pediatric Precautions

Pediatric patients may be more susceptible to topical corticosteroid-induced HPA-axis suppression and Cushing's syndrome than mature individuals because of a greater skin surface area-to-body weight ratio. In open-label studies, adrenal suppression occurred in 14-17% of children 9-12 years of age, 23-32% of children 6-8 years of age, 29-38% of children 2-5 years of age, and 36-50% of infants 3 months to 1 year of age who received topical betamethasone dipropionate creams (including those formulated in an optimized [augmented] vehicle) or ointments for the treatment of atopic dermatitis.209,210,211 HPA-axis suppression, Cushing's syndrome, and intracranial hypertension have occurred in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include retardation of linear growth, delayed weight gain, low plasma cortisol concentrations, and lack of response to corticotropin (ACTH) stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Topical corticosteroid therapy in children should be limited to the minimum amount necessary for therapeutic efficacy; chronic topical corticosteroid therapy may interfere with growth and development. Parents should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, since such garments may constitute occlusive dressings. The manufacturer of Lotrisone^® cream states that use of this preparation in the treatment of diaper dermatitis is not recommended.

Pregnancy, Fertility, and Lactation

Pregnancy

Safe use of topical corticosteroids during pregnancy has not been established. Although there are no adequate and controlled studies to date in humans, potent corticosteroids have been shown to be teratogenic in animals following topical application. Topical corticosteroids should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. The drugs should not be used on extensive areas, in large amounts, or for prolonged periods in pregnant women.

Fertility

It is not known whether topical corticosteroids affect fertility. However, reproduction studies in rats using subcutaneous dosages of clobetasol propionate up to 50 mcg/kg daily have revealed an increase in the incidence of fetal resorption and a decrease in the number of living fetuses at the highest dose.

Lactation

It is not known whether topical corticosteroids are distributed into milk; however, systemic corticosteroids are distributed into milk. Topical corticosteroids should be used with caution in nursing women.

Pharmacology

Following topical application, corticosteroids produce anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Corticosteroids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Corticosteroids, especially the fluorinated corticosteroids, have antimitotic activity on cutaneous fibroblasts and the epidermis.

Tachyphylaxis to the anti-inflammatory effects of the corticosteroids (as shown by vasoconstrictor assay) may occur with repeated application although the clinical importance of this effect is unknown. Following 3-times daily application to normal skin at the same site, diminished vasoconstrictor response may occur within 4-5 days. Withdrawal of the drug for 2-4 days restores response, although maximum vasoconstrictor response may be diminished; when application of the drug is reinstated, tachyphylaxis recurs.

Pharmacokinetics

Percutaneous penetration of corticosteroids varies among individual patients and can be increased by the use of occlusive dressings, by increasing the concentration of the corticosteroid, and by using different vehicles. The use of an occlusive dressing with hydrocortisone for 96 hours substantially enhances percutaneous penetration of the drug; however, such use for up to 24 hours does not appear to alter penetration of topically applied hydrocortisone. Fluorinated corticosteroids apparently do not penetrate the dermis to a greater extent than does hydrocortisone.

Following topical application of a corticosteroid to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation; however, absorption is markedly increased when the skin has lost its keratin layer and can be increased by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema). The drugs are absorbed to a greater degree from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole. Even after washing the area being treated, prolonged absorption of the corticosteroid occurs, possibly because the drug is retained in the stratum corneum.

Topical application of corticosteroids to the mucosa of the genitourinary or lower intestinal tract may result in substantial systemic absorption of the drugs. In healthy individuals, as much as 30-90% of rectally administered hydrocortisone as a retention enema may be absorbed. Greater amounts of hydrocortisone may be absorbed rectally if the intestinal mucosa is inflamed.

Corticosteroids vary in the extent to which they are bound to plasma proteins.

Following percutaneous penetration of a topical corticosteroid, the drug that is systemically absorbed probably follows the metabolic pathways of systemically administered corticosteroids. (See Pharmacokinetics: Elimination, in the Corticosteroids General Statement 68:04.) Corticosteroids usually are metabolized in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites are excreted in bile.

Chemistry

Hydrocortisone or synthetic derivatives of hydrocortisone are used topically as anti-inflammatory agents. These corticosteroids are 21-carbon steroids with the general structure above.

In the corticosteroids, an 11β-hydroxyl group is required for anti-inflammatory activity. Corticosteroids having a ketone group at C 11 (e.g., cortisone and prednisone) must be reduced to their corresponding 11-hydroxyl analogs (hydrocortisone and prednisolone) to be pharmacologically active. This reduction apparently does not occur quickly enough in dermal tissues for these drugs to be effective topically. Anti-inflammatory corticosteroids may have substitutions at positions 6, 9, and 16. Structural modifications of hydrocortisone affect the topical anti-inflammatory activity, and multiple modifications may produce more pronounced effects than would be predicted on the basis of individual changes. The presence of a C 1 to C 2 double bond enhances anti-inflammatory activity. Although substitution of an α-methyl group on C 6 has no consistent effect on activity, a 6α-fluoro substituent enhances anti-inflammatory activity. Substitution of a chlorine atom for the hydroxyl group at position 21 also increases anti-inflammatory activity. Substitution of a fluorine atom in the 9α-position, an acetonide group at positions 16 and 17, omission of the hydroxyl group at position 17 or 21, or esterification of the hydroxyl group at 17 or 21 profoundly increases anti-inflammatory activity. Substitution at C 16 of an α- or β-methyl group has no consistent effect on anti-inflammatory activity.

Only references cited for selected revisions after 1984 are available electronically.

200. Food and Drug Administration. Topical corticosteroids class labeling guideline. (Undated.) Available from: Professional Labeling Branch, Division of Drug Advertising and Labeling, Food and Drug Administration, Rockville, MD.

201. Cornell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol . 1985; 121:63-7. [PubMed 3881088]

202. Cornell RC, Stoughton RB. The use of topical steroids in psoriasis. Dermatol Clin . 1984; 2:397-409.

203. Parish LC, Witkowski JA, Muir JG. Topical corticosteroids. Int J Dermatol . 1985; 24:435-6. [PubMed 4055197]

204. Beveridge GW, Fairburn E, Finn OA et al. A comparison of nystatin cream with nystatin/triamcinolone acetonide combination cream in the treatment of candidal inflammation of the flexures. Curr Med Res Opin . 1977; 4:584-7. [PubMed 326494]

205. Food and Drug Administration. Certain drugs containing antibiotic, corticosteroid, and antifungal components; reevaluation. [Docket No. 84N-0067; DESI No. 10826] Fed Regist . 1985; 50:15227-8.

206. Dermik Laboratories Inc. Psorcon^® ointment prescribing information. Blue Bell, PA; 1985 Oct.

207. Connetics Corp. Olux^® foam 0.05% (clobetasol propionate prescribing information. Palo Alto, CA; 2004 Jan.

208. Connetics Corp, Palo Alto, CA; Personal communication.

209. Schering Corporation. Diprosone^® (betamethasone dipropionate) 0.05% cream prescribing information. Kenilworth, NJ; undated.

210. Schering Corporation. Diprosone^® (betamethasone dipropionate) 0.05% ointment prescribing information. Kenilworth, NJ; 2001 May.

211. Schering Corporation. Diprolene^® AF (augmented betamethasone dipropionate) 0.05% cream prescribing information. Kenilworth, NJ; 2001 Oct.

212. Schering Corporation. Diprolene^® (betamethasone dipropionate) gel 0.05% prescribing information. Kenilworth, NJ; 2000 Jan.

213. GlaxoSmithKline. Temovate E^® (clobetasol propionate) emollient cream 0.05% prescribing information. Pittsburgh, PA; 2002 Aug.

214. GlaxoSmithKline. Temovate^® (clobetasol propionate) gel 0.05% prescribing information. Pittsburgh, PA; 2002 Aug.

215. GlaxoSmithKline. Temovate^® (clobetasol propionate) scalp application 0.05% prescribing information. Pittsburgh, PA; 2002 Aug.

216. Westwood Squibb Pharmaceuticals, Inc. Westcort^® (hydrocortisone valerate) cream 0.2% prescribing information. Princeton, NJ; 2001 Oct.

217. Schering Corporation. Elocon^® (mometasone furoate) cream 0.1% prescribing information. Kenilworth, NJ; 2004 Mar.

218. Schering Corporation. Elocon^® (mometasone furoate) lotion 0.1% prescribing information. Kenilworth, NJ; 2003 Jul.

219. Schering Corporation. Elocon^® (mometasone furoate) ointment 0.1% prescribing information. Kenilworth, NJ; 2002 Nov.

220. Galderma Laboratories. Clobex^® (clobetasol propionate) lotion 0.05% prescribing information. Fort Worth, TX; 2003 Jul.

221. Galderma Laboratories. Clobex^® (clobetasol propionate) shampoo 0.05% prescribing information. Fort Worth, TX; 2004 Jan.

222. Taro. Fluocinonide gel 0.05% prescribing information. Hawthorne, NY; 1997 Jan.

223. Taro. Fluocinonide ointment 0.05% prescribing information. Hawthorne, NY; 1998 Aug.

224. Taro. Fluocinonide topical solution 0.05% prescribing information. Bramalea, ON, Canada; 1998 Feb.

225. Hill. Capex® (fluocinolone acetonide) shampoo 0.01% prescribing information. Sanford, FL; 2000 Jul

226. Fougera. Triamcinolone acetonide cream 0.025%, 0.1%, 0.5% prescribing information. Melville, NY; 2001 Mar.