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  • CLASSES

    Plain Topical Corticosteroids
    Topical Scalp Anti-inflammatories, with Corticosteroids

    DEA CLASS

    Rx

    DESCRIPTION

    Topical, synthetic fluorinated corticosteroid used for moderate-severe corticosteroid-responsive dermatoses, including psoriasis; drug is the most potent topical corticosteroid.

    COMMON BRAND NAMES

    Clobevate, Clobex, Clodan, Cormax, Embeline, Embeline E, Olux, Olux-E, Temovate, Temovate E

    HOW SUPPLIED

    Clobetasol/Clobetasol Propionate/Clobevate/Embeline/Temovate Topical Gel: 0.05%
    Clobetasol/Clobetasol Propionate/Clobex Topical Lotion: 0.05%
    Clobetasol/Clobetasol Propionate/Clobex Topical Spray: 0.05%
    Clobetasol/Clobetasol Propionate/Clobex/Clodan Topical Shampoo: 0.05%
    Clobetasol/Clobetasol Propionate/Cormax/Embeline/Embeline E/Temovate/Temovate E Topical Cream: 0.05%
    Clobetasol/Clobetasol Propionate/Cormax/Embeline/Temovate Topical Sol: 0.05%
    Clobetasol/Clobetasol Propionate/Cormax/Embeline/Temovate/Temovate E Topical Ointment: 0.05%
    Clobetasol/Clobetasol Propionate/Olux/Olux-E Topical Foam: 0.05%

    DOSAGE & INDICATIONS

    For the treatment of moderate-to-severe inflammatory manifestations, including pruritus, of corticosteroid-responsive dermatologic disorders such as alopecia areata, atopic dermatitis, contact dermatitis, generalized exfoliative dermatitis, Rhus dermatitis due to plants like poison ivy, seborrheic dermatitis, eczema (including severe hyperkeratotic eczema, severe nummular eczema, and severe eczematous conditions of the hands or feet), granuloma annulare, keloids, cutaneous lichen planus, lichen simplex chronicus, lichen striatus, subacute cutaneous and discoid lupus erythematosus, pretibial myxedema, necrobiosis lipoidica diabeticorum, pemphigoid, pemphigus, pityriasis rosea, sarcoidosis, sunburn, or urticaria.
    NOTE: Acute exudative inflammation, as occurs with poison ivy, may be best treated with a non-emollient cream or gel formulation, which are drying. Dry, scaly dermatoses may be best treated with emollient creams or ointments. Lower potency corticosteroids should be used on the face and intertriginous areas.
    NOTE: Systemic therapy or intralesional injection of corticosteroids may be necessary for some conditions based on the type and severity of the disorder or inadequate response to topical therapy.
    For the treatment of plaque-type psoriasis.
    Topical dosage (cream, gel, or ointment)
    Adults, Adolescents, and Children >= 12 years

    Apply a thin layer to the affected skin areas twice daily, once in the morning and once at night. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Neonates, Infants, and Children < 12 years

    Safety and efficacy have not been established.

    Topical dosage (emollient cream ONLY)
    Adults and Adolescents >= 16 years

    Apply a thin layer to the affected skin areas twice daily, once in the morning and once at night. Treatment must be limited to 2 consecutive weeks if the body surface area treated is > 10%. If the body surface area treated is 5—10%, treatment can be extended to 4 consecutive weeks. Amounts greater than 50 g per week should not be used. In one study of 35 patients, use of 0.4—0.5 gm twice daily of clobetasol propionate emollient cream was significantly more effective than the emollient vehicle alone in reducing symptoms after 4 weeks of treatment and at the 2 week post-treatment follow-up period. No significant adverse events were noted.

    Topical dosage (foam)
    Adults, Adolescents, and Children >= 12 years

    Apply to the psoriatic areas twice daily, once in the morning and once at night. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Topical dosage (spray solution)
    Adults

    Spray directly onto the affected area twice daily, once in the morning and once at night, for up to 4 consecutive weeks. After the first 2 weeks, limit  use to localized lesions of moderate to severe plaque psoriasis that have not shown significant improvement. Do not exceed 50 grams (one 59 mL bottle) per week.

    Topical dosage (lotion ONLY)
    Adults

    Apply to the affected areas twice daily, once in the morning and once at night. Rub in gently and completely. May be used for up to 4 consecutive weeks; limit use beyond 2 weeks to very localized treatment of unresolved moderate to severe plaque psoriasis (not to exceed 10% of body surface area). Recommended maximum dose of 50 grams per week.

    Topical dosage (scalp solution)
    Adults, Adolescents, and Children >= 12 years

    Apply to the psoriatic scalp areas twice daily, once in the morning and once at night. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Topical dosage (shampoo)
    Adults

    Once daily, apply to dry, psoriatic scalp areas, leave in place for 15 minutes, then lather and rinse. Limit treatment to 4 consecutive weeks and a maximum of 50 ml or 50 gram weekly.

    For the alternative treatment of recalcitrant oral vesiculoerosive disease† including oral lichen planus†, mucous membrane pemphigus†, aphthous ulcer† and chronic oral erythema multiforme†.
    Topical dosage (Dental topical preparation† of clobetasol ointment in Orabase)
    Adults

    Apply a thin coating directly to the lesion(s) twice daily until signs and symptoms have receded. In one double-blind clinical trial, 55 patients were treated up to 4 weeks with either clobetasol propionate or fluocinonide ointment in Orabase. Both medications provided relief of pain and erythema, and decreased lesion size. Common side effects included oral candidiasis, hypogeusia, and burning sensation at the site of application.

    Topical dosage (non-emollient cream ONLY)
    Adults, Adolescents, and Children >= 12 years

    Apply a thin layer to the affected skin areas twice daily, in the morning and in the evening. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Children†

    Safety and efficacy have not been established and use is not recommended by manufacturer. In one study, the cream was applied once daily to the affected areas without occlusion for the treatment of atopic dermatitis. Clobetasol propionate treatment at this dose was associated with a fall in serum cortisol levels. In another small trial, clobetasol butyrate 0.05% cream (not available in the US) applied to the atopic areas twice daily for 4 weeks was reported effective. Urinary cortisol excretion was not altered by the clobetasol butyrate treatment, which was compared to fluticasone propionate 0.05% cream.

    Topical dosage (emollient cream ONLY)
    Adults and Adolescents >= 16 years

    Apply a thin layer to the affected skin areas twice daily, once in the morning and once at night. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Topical dosage (topical/scalp solution)
    Adults, Adolescents, and Children >= 12 years

    Apply to the affected scalp areas twice daily, once in the morning and once at night. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Topical dosage (gel, foam, and ointment)
    Adults, Adolescents, and Children >= 12 years

    Apply to the affected areas twice daily, once in the morning and once at night. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams per week.

    Topical dosage (lotion ONLY)
    Adults

    Apply to the affected areas twice daily, once in the morning and once at night. Rub in gently and completely. Limit treatment to 2 consecutive weeks and a maximum dose of 50 grams (50 ml or 1.75 fluid ounces) per week.

    For the treatment of vulvar lichen sclerosus†.
    Topical dosage (cream)
    Adult females

    Apply a thin layer to the affected vulvar, labial, and perineal areas twice daily, once in the morning and once at night. Treatment must be limited to 2 consecutive weeks, and amounts greater than 50 g per week should not be used. In a retrospective, uncontrolled analysis of 36 women with biopsy-proven lichen sclerosis, the initial clobetasol treatment course provided remission of symptoms in 77% of patients, and 47% noted an improvement in tissue appearance at one year of follow-up. The authors noted that intermittent clobetasol applications may be needed to maintain results.

    For the alternative treatment of vision-threatening periocular capillary hemangioma† in infancy and early childhood.
    Topical dosage (cream)
    Children and Infants

    Limited reports have used topical clobetasol propionate cream as an alternative to intralesional corticosteroid injections. Treatment was prescribed with 0.05% clobetasol propionate cream applied to the area twice daily for 2 weeks, followed by a 1-week intermission. The cycle was repeated as needed. The 3 cases responded within 4 months to the topical treatment. Children were closely monitored for adrenal suppression. Clobetasol application was reserved for instances in which the risks of the disease (e.g., permanent visual loss) to the infant or the young child outweighed the potential risks of clobetasol treatment. Because the involution of the hemangioma occurs at a slower rate than would intralesional injection, topical clobetasol would not be appropriate in instances of acute, severe visual axis occlusion.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    50 mL/week scalp or topical solutions and shampoo; 59 mL/week spray solution; 50 g/week other topicals.

    Geriatric

    50 mL/week scalp or topical solutions and shampoo; 59 mL/week spray solution; 50 g/week other topicals.

    Adolescents

    >= 16 years: Safety and efficacy of lotion, shampoo, and spray solution have not been established; 50 g/week of other formulations.
    13 to < 16 years: Safety and efficacy of emollient cream, lotion, shampoo, and spray solution have not been established; 50 g/week of other formulations.

    Children

    >= 12 years: Safety and efficacy of emollient cream, lotion, shampoo, and spray solution have not been established; 50 g/week of other formulations.
    < 12 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: Best results are obtained when topical corticosteroids of adequate strength are used for specified lengths of time. Patients who fail to respond to clobetasol treatment after 1—4 weeks should be re-evaluated.
    NOTE: Discontinue once control of the treated condition has been achieved. Intermittent application may need to be continued to maintain remission or control of the condition in some cases. Some authorities recommend cyclic applications (i.e., 2 weeks of clobetasol treatment followed by 1 week of lubrication only) for chronic conditions like psoriasis. The lowest effective maintenance application should be used. Other options include changing to a less potent topical corticosteroid for maintenance and control of inflammation and symptoms.

    Topical Administration

    For topical dermatologic use only. Not for ophthalmic, oral, or intravaginal use. Generally not recommended for use on the face or intertriginous areas.
    Restrict application to the active lesions or affected areas and try to avoid normal surrounding skin.
    Do not use clobetasol propionate preparations with occlusive dressings. Instruct patients not to bandage, cover, or wrap area in any way that may be occlusive.

    Cream/Ointment/Lotion Formulations

    Cream, emollient cream, gel, or ointment:
    Wash hands before and after application. Use gloves if required by universal precautions. Apply sparingly in a thin film and rub gently into affected area.
    The amount of cream or ointment needed to cover a certain area can be calculated. A 1 g application of cream covers 100 cm2 of skin. The entire skin surface of the average size adult will be covered by 30 g of topical steroid cream.

    Other Topical Formulations

    Scalp solution:
    Wash hands before and after application. Use gloves if required by universal precautions. Apply sparingly in a thin film to the affected areas of the scalp; rub in gently and completely.
    Topical foam: 
    Invert the can and dispense a small amount of foam (up to a maximum of a golf-ball-size dollop) into the cap of the can, onto a saucer or other cool surface, or directly on the lesion, taking care to avoid contact with the eyes. Dispensing directly onto hands is not recommended, as the foam will begin to melt immediately upon contact with warm skin. If applying to the scalp, move the hair away from the affected area so that the foam can be applied. Gently massage into affected scalp area until the foam disappears. Repeat until entire affected area is treated. Wash hands before and after treatment.
    Topical spray: 
    Wash hands before and after treatment. Spray directly onto the affected skin areas; rub in gently but completely.
    Topical shampoo: 
    Wash hands before and after treatment. Do not wet hair prior to use. Apply directly to the affected area of the scalp. Rub in gently; leave on the scalp for 15 minutes. Instruct patients not to cover their head while the shampoo is on the scalp. After 15 minutes, add water, lather and rinse completely.

    Extemporaneous Compounding-Topical

    Dental topical preparation for application to oral vesiculoerosive disease:
    NOTE: Clobetasol is not approved by the FDA for dental administration.
    An extemporaneous preparation of clobetasol for buccal or oral mucous membrane application can be compounded by combining clobetasol propionate ointment in a 1:1 ratio with a plasticized hydrocarbon gel (Orabase-plain). No stability data are currently available.

    STORAGE

    Clobevate:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Clobex:
    - Protect from freezing
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Clodan:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Cormax:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Embeline:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Embeline E:
    - Do not refrigerate
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Olux:
    - Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Olux-E:
    - Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
    - Flammable, keep away from heat and flame
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Olux-Olux-E Complete Pack:
    - Avoid exposure to heat
    - Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Temovate:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Temovate E:
    - Do not refrigerate
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Corticosteroid hypersensitivity

    Clobetasol is contraindicated in any patient with a history of corticosteroid hypersensitivity and hypersensitivity to clobetasol or any ingredients in the preparation. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to clobetasol should not receive any form of clobetasol. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.

    Cushing's syndrome, hepatic disease, hypothalamic-pituitary-adrenal (HPA) suppression, occlusive dressing, skin abrasion

    Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing's syndrome in some patients. Clobetasol propionate has been shown to suppress the HPA axis at doses as low as 2 g/day. Conditions which increase systemic absorption include application of high-potency corticosteroids, use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), use in pediatric patients, use in patients with hepatic disease, and the use of an occlusive dressing. Clobetasol propionate preparations should not be used with occlusive dressings. Patients receiving large doses of a potent topical corticosteroid like clobetasol should be evaluated periodically for evidence of HPA axis suppression and manifestations of Cushing's syndrome. If these effects are noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation. Infrequently, signs and symptoms of withdrawal may occur, requiring supplemental systemic corticosteroids. It is recommended that the administration of clobetasol creams, ointments, gels, or topical solutions be limited to no more than 14 days duration, in order to limit the risk of systemic effects. Clobetasol propionate emollient creams may be administered for up to 4 weeks duration if applied to no more than 5—10% of body surface area. The total weekly dose limit of 50 g or 50 mL of a 0.05% preparation should not be exceeded for any clobetasol preparation.

    Diabetes mellitus

    Topical corticosteroids, including clobetasol, should be used with caution in patients with diabetes mellitus. Exacerbation of diabetes may occur with systemic absorption of the topical corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in diabetic patients.

    Children, growth inhibition, increased intracranial pressure, infants, neonates

    Efficacy and adverse reaction data in the pediatric population are limited for topical clobetasol; therefore use in neonates, infants, or children under 12 years of age is not recommended. Children and infants may absorb proportionally larger amounts of topical corticosteroids due to a larger skin surface area to body weight ratio, and therefore are more susceptible to developing systemic toxicity, especially with very-high-potency products. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, growth inhibition (linear growth retardation and delayed weight gain), and increased intracranial pressure have been reported in children receiving topical corticosteroids. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Clobetasol is not approved to treat diaper dermatitis. If children are being treated in the diaper area, tight-fitting diapers or plastic pants should be avoided as these garments may act as an occlusive dressing and increase systemic absorption of the drug.

    Pregnancy

    Clobetasol is classified as FDA pregnancy risk category C. Corticosteroids have been shown to be teratogenic after dermal, oral, and subcutaneous administration in laboratory animals. There are no adequate and well-controlled studies of teratogenic effects from topical application of clobetasol in pregnant women. Clobetasol has greater potency, and thus greater teratogenic potential, than other topical corticosteroids. According to the manufacturer, clobetasol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids, including clobetasol, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women.

    Breast-feeding

    Clobetasol has not been studied during breast feeding, however cortisol is a normal component of breast milk. While the American Academy of Pediatrics does not comment on the use of clobetasol during breast-feeding, it does consider some systemic corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding. It is not known whether topical administration of clobetasol could result in sufficient systemic absorption to produce detectable quantities in breast milk; however, increased blood pressure has been reported in an infant whose mother applied a topical corticosteroid ointment directly to the nipples. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application. Most authorities recommend caution when prescribing topical corticosteroids to breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Fungal infection, herpes infection, infection, measles, peripheral vascular disease, varicella, viral infection

    The normal inflammatory response to local infections can be masked by clobetasol. Application of topical corticosteroids to areas of infection, including tuberculosis of the skin, dermatologic fungal infection, and cutaneous or systemic viral infection (e.g., herpes infection, measles, varicella), should be initiated or continued only if the appropriate anti-infective treatment is instituted. If the infection does not respond to the antimicrobial therapy, the concurrent use of the topical corticosteroid should be discontinued until the infection is controlled. Topical corticosteroids may delay the healing of non-infected wounds, such as venous stasis ulcers. Use clobetasol preparations with caution in patients with markedly impaired circulation or peripheral vascular disease; skin ulceration has been reported in these patients following topical corticosteroid use.

    Acne rosacea, acne vulgaris, cataracts, glaucoma, ocular exposure, ophthalmic administration, perioral dermatitis

    As with other potent fluorinated topical corticosteroids, clobetasol should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis. Clobetasol may aggravate these conditions. Clobetasol preparations should not be applied to the face, groin, or axillae. Care should be taken to avoid use around the eyes; ophthalmic administration should be avoided. Visual impairment, ocular hypertension and worsened cataracts have been reported with ocular exposure to other high potency topical corticosteroids. Preexisting glaucoma may be aggravated if clobetasol is used in the periorbital area.

    Geriatric, skin atrophy

    Topical corticosteroids should be used for brief periods, or under close medical supervision in patients with evidence of pre-existing skin atrophy. Geriatric patients may be more likely to have preexisting skin atrophy secondary to aging. Purpura and skin lacerations that may raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the use of topical corticosteroids in geriatric patients. Topical clobetasol clinical trials included insufficient numbers of elderly patients to do a separate analysis of efficacy and safety in this population. Based on available data, no dosage adjustments are required for elderly patients receiving topical clobetasol. Use of lower potency topical corticosteroids also may be necessary in some patients.

    Tobacco smoking

    The foam formulation of clobetasol is flammable. Avoid use near a fire or flame, including tobacco smoking during or immediately after application.

    ADVERSE REACTIONS

    Severe

    skin atrophy / Delayed / 0-2.0
    papilledema / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    visual impairment / Early / Incidence not known
    ocular hypertension / Delayed / Incidence not known

    Moderate

    erythema / Early / 1.0-10.0
    withdrawal / Early / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    Cushing's syndrome / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    cataracts / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known

    Mild

    maculopapular rash / Early / 1.0-10.0
    pruritus / Rapid / 1.0-10.0
    skin irritation / Early / 2.0-10.0
    xerosis / Delayed / 1.0-10.0
    striae / Delayed / 0-2.0
    acneiform rash / Delayed / 0-2.0
    infection / Delayed / 0-2.0
    skin hypopigmentation / Delayed / 0-2.0
    folliculitis / Delayed / 0-2.0
    miliaria / Delayed / 0-2.0
    hypertrichosis / Delayed / 0-2.0
    telangiectasia / Delayed / 0-2.0
    vesicular rash / Delayed / 0.3-0.3
    ocular irritation / Rapid / 0.3-0.3
    alopecia / Delayed / 0.3-0.3
    headache / Early / 0.3-0.3

    DRUG INTERACTIONS

    Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
    Metyrapone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.

    PREGNANCY AND LACTATION

    Pregnancy

    Clobetasol is classified as FDA pregnancy risk category C. Corticosteroids have been shown to be teratogenic after dermal, oral, and subcutaneous administration in laboratory animals. There are no adequate and well-controlled studies of teratogenic effects from topical application of clobetasol in pregnant women. Clobetasol has greater potency, and thus greater teratogenic potential, than other topical corticosteroids. According to the manufacturer, clobetasol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids, including clobetasol, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women.

    Clobetasol has not been studied during breast feeding, however cortisol is a normal component of breast milk. While the American Academy of Pediatrics does not comment on the use of clobetasol during breast-feeding, it does consider some systemic corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding. It is not known whether topical administration of clobetasol could result in sufficient systemic absorption to produce detectable quantities in breast milk; however, increased blood pressure has been reported in an infant whose mother applied a topical corticosteroid ointment directly to the nipples. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application. Most authorities recommend caution when prescribing topical corticosteroids to breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2 , an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.

    PHARMACOKINETICS

    Clobetasol is administered topically to the skin as a cream, gel, ointment, or topical solution.
     
    Because clobetasol is fluorinated and also contains a substituted 17-hydroxyl group, it is not metabolized in the skin. Repeated application results in a cumulative depot effect in the skin, which may lead to a prolonged duration of action and increased systemic absorption. Due to the fact that circulating levels are below the level of detection, the use of pharmacodynamic endpoints for assessing the systemic exposure of topical clobetasol is necessary. Once in the systemic circulation, clobetasol is metabolized in the liver, but systemic metabolism has not been fully quantified. Excretion of clobetasol propionate and its metabolites occurs via the urine and bile.

    Topical Route

    The extent of percutaneous absorption of the topical corticosteroids is dependent on many factors, including the pharmaceutical vehicle and the integrity of the epidermis. Absorption after topical application of clobetasol is increased in areas that have skin damage, inflammation, or occlusion, or in areas where the stratum corneum is thin such as the eyelids, genitalia, axillae, and face. The use of occlusive dressings with the application of clobetasol enhances penetration into the skin, and may increase the chance of systemic absorption. Ointments have a hydrating effect, are lipophilic, and enhance the penetration of clobetasol into the skin. Clobetasol gels, foams, and solutions also have enhanced topical penetration versus cream preparations. Once absorbed, maximal vasoconstrictive effects of clobetasol occur within 1.5 hours of application. Anti-inflammatory effects are usually not seen for hours after clobetasol application, since the mechanism of action requires alterations in synthesis of proteins.