Clobetasol Propionate Vaginal Cream

Overview of Clobetasol Propionate Vaginal Cream

Dosage Strength of Clobetasol Propionate Vaginal Cream

0.05% 30 mL Pump

General Information

Clobetasol is a topical, synthetic fluorinated corticosteroid. Clobetasol is used to relieve the inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses and psoriasis. Clobetasol is one of the most potent topical corticosteroids, and is usually recommended for short-term or cyclic therapy only. Very high potency topical corticosteroids are used as an alternative to systemic therapy for localized conditions. Long-term use can lead to systemic side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression. Clobetasol was first approved by the FDA in 1985.

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.

Route-Specific Pharmacokinetics:

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.

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.

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.1

Children†: Safety and efficacy have not been established and use is not recommended by manufacturer.1 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.2

Neonates and Infants: Safety and efficacy have not been established.

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.1

Neonates, Infants, and Children < 12 years: Safety and efficacy have not been established.

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.3

† Off-label indication

Contraindications/Precautions

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.4

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.5

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.

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.5 6

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. Guidelines recommend mild to moderate potency agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birthweight has been reported with use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. There are no adequate and well-controlled studies of teratogenic effects from topical application of clobetasol in pregnant women. Corticosteroids have been shown to be teratogenic after dermal, oral, and subcutaneous administration in animal studies. Clobetasol has greater potency, and thus greater teratogenic potential, than other topical corticosteroids. After subcutaneous clobetasol propionate administration to pregnant mice and rabbits, increased malformations, such as cleft palate and skeletal abnormalities, were observed.7 8 9 10 11

It is not known whether topical administration of clobetasol could result in sufficient systemic absorption to produce detectable quantities in breast milk to cause issues during breast-feeding; the manufacturers recommend to use with caution.7 8 9 10 However, most dermatologists stress that topical corticosteroids can be safely used during lactation.12 If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. 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.

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.

As with other potent fluorinated topical corticosteroids, clobetasol should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis as clobetasol may aggravate these conditions. Clobetasol preparations should not be applied to the face, groin, vagina, or axillae. Care should be taken to avoid use around the eyes; ocular exposure should be avoided. If unintended contact happens, the patient should rinse the exposed area well with water. Visual impairment, ocular hypertension and 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. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.7 8 9 10

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.

The foam formulation of clobetasol is flammable. Avoid use near a fire or flame, including tobacco smoking during or immediately after application.5

Pregnancy

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. Guidelines recommend mild to moderate potency agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birthweight has been reported with use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. There are no adequate and well-controlled studies of teratogenic effects from topical application of clobetasol in pregnant women. Corticosteroids have been shown to be teratogenic after dermal, oral, and subcutaneous administration in animal studies. Clobetasol has greater potency, and thus greater teratogenic potential, than other topical corticosteroids. After subcutaneous clobetasol propionate administration to pregnant mice and rabbits, increased malformations, such as cleft palate and skeletal abnormalities, were observed.7 8 9 10 11

Breast-feeding

It is not known whether topical administration of clobetasol could result in sufficient systemic absorption to produce detectable quantities in breast milk to cause issues during breast-feeding; the manufacturers recommend to use with caution.7 8 9 10 However, most dermatologists stress that topical corticosteroids can be safely used during lactation.12 If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. 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.

Adverse Reactions/Side Effects

When used for recommended treatment periods of 14 days or less, clobetasol topical preparations are usually well tolerated. The most frequently reported adverse reactions to clobetasol therapy are local in nature and include burning sensations, pruritus, and skin irritation. Burning and stinging sensations are more common with gel, emollient cream, and topical scalp foam/solution preparations of clobetasol and occur in 2—10% of patients. Other local adverse reactions reported in less than 2% of patients treated with clobetasol include acneiform rash, transient erythema, folliculitis, miliaria, perioral dermatitis, secondary infection, skin atrophy, skin hypopigmentation, skin peeling or cracking, xerosis, hypertrichosis, telangiectasia, and striae. Purpura and maculopapular rash may also occur. Additional adverse reactions related to scalp application of clobetasol include alopecia, vesicular rash, ocular irritation, and headache in roughly 0.3% of patients. Headache may be a clinical sign of elevated intracranial pressure. Adverse dermatologic effects are more likely to occur in intertriginous and facial areas, and tend to be more severe with fluorinated topical corticosteroids like clobetasol. Adverse dermatologic side effects of clobetasol are also more frequent with concurrent use of occlusive dressings. Some dermatologic effects, such as skin atrophy and striae, occur even with intermittent applications of high-potency topical corticosteroids, and may be permanent with prolonged treatment. If irritation develops, discontinue topical corticosteroids and institute appropriate therapy. The anti-inflammatory activity of topical corticosteroids may mask manifestations of infection. In the presence of dermatological infections, institute the use of an appropriate antifungal or antibacterial agent. If a favorable response does not promptly occur, discontinue the corticosteroid until the infection has been adequately controlled.

Signs and symptoms of corticosteroid withdrawal may occur with clobetasol dose reduction or discontinuation, and supplemental systemic corticosteroids may be needed. For example, disease flare may occur and HPA axis suppression may be present.

Systemic absorption of topical corticosteroids such as clobetasol can produce reversible hypothalamic-pituitary-adrenal (HPA) suppression with possible adrenocortical insufficiency after treatment discontinuation. In some patients, systemic absorption can produce manifestations of Cushing's syndrome, hypertension, hyperglycemia, and glycosuria. Percutaneous absorption of clobetasol is dependent on many factors including the vehicle, the integrity of the epidermal barrier, duration of use, and use of an occlusive dressing. Children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. HPA axis suppression and increased intracranial pressure have been reported in children receiving topical corticosteroids. Manifestations of adrenocortical insufficiency in children include linear growth inhibition, delayed weight gain, low plasma cortisol concentrations, and absence of response to ACTH stimulation. Clinical signs of increased intracranial pressure include bulging fontanelles, headaches, and bilateral papilledema (i.e., pseudotumor cerebri). Clobetasol is a very-high-potency corticosteroid, and the risk of HPA axis suppression is greater than with other topical corticosteroids. However, the risk appears to be dose related. It is estimated that after 1 week of use of clobetasol at a dose of 3.5 grams twice daily (i.e., a 50-gram tube of clobetasol per week) over a 30% body surface area, 75% of adult patients will experience some degree of HPA axis suppression. In contrast, only 10% of adult patients using the equivalent of one 15-gram tube of clobetasol per week will have HPA axis suppression. One 4-week study of clobetasol emollient cream used in doses of 0.4—0.5 g twice daily in adult patients with plaque-type psoriasis resulted in no significant effects on serum cortisol concentrations or tolerability.13 Periodically evaluate patients applying clobetasol to a large surface area or to areas under occlusion for evidence of HPA axis suppression (using the ACTH stimulation test and urinary free cortisol test). To minimize risk of HPA axis suppression, discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, reduce the frequency of application, or substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid.

Case reports describe the development of extensive visual impairment in patients secondary to the onset of glaucoma or ocular hypertension during the use of potent topical corticosteroids to treat severe atopic eczema of the face. Such adverse effects, if they occur, could lead to blindness. Cataracts have also been reported, usually with large doses or therapy greater than 6 months. The use of topical corticosteroids may also increase the risk of posterior subcapsular cataracts and retinopathy (central serous chorioretinopathy). Clobetasol is generally not recommended for application to the face. Any patient who develops changes in vision while applying clobetasol to the scalp or other areas should be evaluated for ocular hypertension. Low potency corticosteroids (e.g., hydrocortisone, dexamethasone) have been reported to be safer for short-term use around the eye area.78 9 10

In general, excessive use of corticosteroids can lead to impaired wound healing. Since clobetasol is a topical corticosteroid, it should not be applied directly on or near healing wounds. A propensity for skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.

Tolerance may occur with the prolonged use of topical corticosteroids. Tolerance is usually described as a decreased acute vasoconstrictive response to the agent after a period of days to weeks. This may explain the dramatic responses noted initially by patients early in topical corticosteroid treatment and an apparent diminished response with time. Tolerance is reversible and may be attenuated by interrupted or cyclic schedules of application (e.g., clobetasol is given twice daily for 2—3 weeks, followed by a 1-week intermission).

Allergic contact dermatitis with corticosteroids such as clobetasol is usually diagnosed by observing a failure to heal. Appropriate diagnostic patch testing may help with the diagnosis.

Storage

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

  • 1. a. b. c. Clobetasol propionate cream, gel, and ointment package insert. Melville, NY: E. Fougera & Co.; 2007 Dec.
  • 2. Wolkerstorfer A, Strobos MA, Glazenberg EJ, et al. Fluticasone propionate 0.05% cream once daily versus clobetasol butyrate 0.05% cream twice daily in children with atopic dermatitis. J Am Acad Dermatol 1998;39:226-31.
  • 3. Lorenz B, Kaufman RH, Kutzner SK. Lichen sclerosus. Therapy with clobetasol propionate. J Reprod Med 1998;43:790-4.
  • 4. Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol 2002;89(5):439-445.
  • 5. a. b. c. Olux (clobetasol propionate) Foam package insert. Research Triangle Park, NC: Stiefel Laboratories, Inc.; 2018 Apr.
  • 6. Temovate (clobetasol propionate gel) package insert. Pittsburgh, PA: GSK Consumer Healthcare LP; 2002 Aug.
  • 7. a. b. c. d. e. f. Temovate-E (clobetasol propionate) emollient cream package insert. Duluth, GA: PharmaDerm; 2006 Mar.
  • 8. a. b. c. d. e. f. Olux-E (clobetasol propionate) Foam package insert. Research Triangle Park, NC: Stiefel Laboratories, Inc; 2018 May.
  • 9. a. b. c. d. e. f. Clobex Spray (clobetasol propionate) package insert. Fort Worth, TX: Galderma Laboratories; 2012 Aug.
  • 10. a. b. c. d. e. f. Impoyz (clobetasol propionate) cream 0.025% package insert. San Antonio, TX: Promius Pharma, LLC: 2017 Nov.
  • 11. a. b. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy. J Am Acad Dermatol. 2014;70:401.e1-14. Review.
  • 12. a. b. Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II. Lactation. J Am Acad Dermatol. 2014;70:417.e1-10. Review.
  • 13. Jorizzo JL, Magee K, Stewart DM, et al. Clobetasol propionate emollient 0.05%: hypothalamic-pituitary-adrenal-axis safety and four-week clinical efficacy results in plaque-type psoriasis. Cutis 1997;60:55-60.

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