Clobetasol Propionate

None. None.

• Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested. ( Error! Hyperlink reference not valid. )
• Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. ( Error! Hyperlink reference not valid. )
• Systemic absorption may require periodic evaluation for HPA axis suppression. Modify use if HPA axis suppression develops. ( Error! Hyperlink reference not valid. )
• Children may be more susceptible to systemic toxicity from use of topical corticosteroids. ( Error! Hyperlink reference not valid. , 8.4)
• Clobetasol propionate spray may increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. ( Error! Hyperlink reference not valid. )
• Local adverse reactions with topical corticosteroids may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. ( Error! Hyperlink reference not valid. )
• Clobetasol propionate spray is flammable; keep away from heat or flame. ( Error! Hyperlink reference not valid. ) 5.1 Effects on the Endocrine System Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested. Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, using the Cosyntropin Stimulation Test, clobetasol propionate spray, 0.05% demonstrated rates of suppression that were comparable after 2 and 4 weeks of twice-daily use (19% and 15 to 20%, respectively), in adult patients with moderate to severe plaque psoriasis (≥20% BSA). In these studies, HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30 minutes post cosyntropin stimulation [ see Clinical Pharmacology ( 12 ) ]. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure. An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure. Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids [ see Use in Specific Populations ( 8.4 ) ]. 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids, including clobetasol propionate spray, may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including topical clobetasol products [ see Adverse Reactions ( 6.2 ) ].
• Avoid contact of clobetasol propionate spray with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Local Adverse Reactions with Topical Corticosteroids The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence:
• folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria. 5.4 Allergic Contact Dermatitis Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing. 5.5 Concomitant Skin Infections In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of clobetasol propionate spray, 0.05% should be discontinued until the infection has been adequately controlled. 5.6 Flammable Contents Clobetasol propionate spray, 0.05% is flammable; keep away from heat or flame.

• Risk Summary There are no available data on clobetasol propionate spray use in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Observational studies suggest an increased risk of low birthweight in infants with the maternal use of potent or very potent topical corticosteroids ( see Data ).
• Advise pregnant women that clobetasol propionate spray may increase the risk of having a low birth weight infant and to use clobetasol propionate spray on
• the smallest area of skin and for the shortest duration possible.
• Animal reproduction studies have not been conducted with clobetasol propionate spray.
• In an animal reproduction study, subcutaneous administration of clobetasol propionate to pregnant rats at doses greater than 12.5 mcg/kg/day during the period of organogenesis caused an increase in malformations (increased incidence of umbilical hernia) ( see Data ).
• The available data do not allow calculation of relevant comparisons between the systemic exposure of clobetasol propionate in animal studies to the systemic exposure that would be expected in humans after topical use of clobetasol propionate spray.
• The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
• All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
• In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
• Data Human Data Available observational studies in pregnant women did not identify a drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency.
• However, when the dispensed amount of potent or very potent topical corticosteroids exceeded 300 g during the entire pregnancy, maternal use was associated with an increased risk of low birth weight in infants.
• Animal Data Clobetasol propionate is absorbed percutaneously, and when administered subcutaneously it caused malformations in both the rabbit and the mouse.
• Clobetasol propionate has greater potential for adverse developmental effects than steroids that are less potent.
• The effect of clobetasol propionate on pregnancy outcome and development of offspring was studied in the rat.
• Clobetasol propionate was administered subcutaneously to female rats twice daily (0, 12.5, 25, and 50 mcg/kg/day) from day 7 of presumed gestation through day 25 of lactation or day 24 presumed gestation for those rats that did not deliver a litter.
• The maternal no-observed-adverse-effect-level (NOAEL) for clobetasol propionate was less than 12.5 mcg/kg/day due to reduced body weight gain and feed consumption during the gestation period.
• The reproductive NOAEL in the dams was 25 mcg/kg/day based on prolonged delivery at 50 mcg/kg/day.
• The NOAEL for viability and growth in the offspring was 12.5 mcg/kg/day based on incidence of stillbirths, reductions in pup body weights on days 1 and 7 of lactation, increased pup mortality, increases in the incidence of umbilical hernia, and increases in the incidence of pups with cysts on the kidney at higher dose levels during the preweaning period.
• The weights of the epididymides and testes were significantly reduced at higher dosages.
• Despite these changes, there were no effects on the mating and fertility of the offspring.
• IN SPECIFIC POPULATIONS
• 8.1 Pregnancy Risk Summary There are no available data on clobetasol propionate spray use in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Observational studies suggest an increased risk of low birthweight in infants with the maternal use of potent or very potent topical corticosteroids ( see Data ).
• Advise pregnant women that clobetasol propionate spray may increase the risk of having a low birth weight infant and to use clobetasol propionate spray on
• the smallest area of skin and for the shortest duration possible.
• Animal reproduction studies have not been conducted with clobetasol propionate spray.
• In an animal reproduction study, subcutaneous administration of clobetasol propionate to pregnant rats at doses greater than 12.5 mcg/kg/day during the period of organogenesis caused an increase in malformations (increased incidence of umbilical hernia) ( see Data ).
• The available data do not allow calculation of relevant comparisons between the systemic exposure of clobetasol propionate in animal studies to the systemic exposure that would be expected in humans after topical use of clobetasol propionate spray.
• The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
• All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
• In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
• Data Human Data Available observational studies in pregnant women did not identify a drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency.
• However, when the dispensed amount of potent or very potent topical corticosteroids exceeded 300 g during the entire pregnancy, maternal use was associated with an increased risk of low birth weight in infants.
• Animal Data Clobetasol propionate is absorbed percutaneously, and when administered subcutaneously it caused malformations in both the rabbit and the mouse.
• Clobetasol propionate has greater potential for adverse developmental effects than steroids that are less potent.
• The effect of clobetasol propionate on pregnancy outcome and development of offspring was studied in the rat.
• Clobetasol propionate was administered subcutaneously to female rats twice daily (0, 12.5, 25, and 50 mcg/kg/day) from day 7 of presumed gestation through day 25 of lactation or day 24 presumed gestation for those rats that did not deliver a litter.
• The maternal no-observed-adverse-effect-level (NOAEL) for clobetasol propionate was less than 12.5 mcg/kg/day due to reduced body weight gain and feed consumption during the gestation period.
• The reproductive NOAEL in the dams was 25 mcg/kg/day based on prolonged delivery at 50 mcg/kg/day.
• The NOAEL for viability and growth in the offspring was 12.5 mcg/kg/day based on incidence of stillbirths, reductions in pup body weights on days 1 and 7 of lactation, increased pup mortality, increases in the incidence of umbilical hernia, and increases in the incidence of pups with cysts on the kidney at higher dose levels during the preweaning period.
• The weights of the epididymides and testes were significantly reduced at higher dosages.
• Despite these changes, there were no effects on the mating and fertility of the offspring.
• 8.2 Lactation Risk Summary There is no information regarding the presence of clobetasol propionate in human milk or its effects on the breastfed infant or on milk production.
• It is not known whether topical administration of clobetasol propionate could result in sufficient systemic absorption to produce detectable quantities in human milk.
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clobetasol propionate spray and any potential adverse effects on the breastfed infant from clobetasol propionate spray or from the underlying maternal condition.
• Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use clobetasol propionate spray on
• the smallest area of skin and for the shortest duration possible while breastfeeding.
• Advise breastfeeding women not to apply clobetasol propionate spray directly to the nipple and areola to
• avoid direct infant exposure [ see Use in Specific Populations ( 8.4 ) ].
• 8.4 Pediatric Use Use in patients under 18 years of age is not recommended, because safety has not been established and because numerically high rates of HPA axis suppression were seen with other clobetasol propionate topical formulations.
• Safety and effectiveness in pediatric patients treated with clobetasol propionate spray, 0.05% have not been established [ see Warnings and Precautions (5.1) ].
• Because of higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than
• adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids.
• They are therefore also at greater risk of glucocorticosteroid insufficiency during and/or after withdrawal of treatment.
• Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.
• HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids.
• Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation.
• Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
• 8.5 Geriatric Use Clinical studies of clobetasol propionate spray, 0.05% did not include sufficient numbers of patients aged 65 and over to adequately determine whether they respond differently than younger patients.
• In two randomized, vehicle controlled clinical trials, 21 of the 240 patients (9%) were over the age of 65.
• In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Topically applied clobetasol propionate spray, 0.05% can be absorbed in sufficient amount to produce systemic effects [ see Warnings and Precautions (5.1) ].