Spectro

Indicação

O spray CLOBEX®, 0,05%, é uma formulação tópica de corticosteróide potente super alta, indicada para o tratamento da psoríase em placas moderada a grave que afeta até 20% da área da superfície corporal (BSA) em pacientes com 18 anos ou mais. A dosagem total não deve exceder 50 g (59 mL ou 2 fl. oz.) por semana. Não use mais de 26 sprays por aplicação ou 52 sprays por dia. O tratamento deve ser limitado a 4 semanas consecutivas.

Os pacientes devem ser instruídos a usar o spray CLOBEX®, 0,05% pelo tempo mínimo necessário para alcançar os resultados desejados. O uso em pacientes com menos de 18 anos de idade não é recomendado porque a segurança não foi estabelecida e porque foram observadas taxas numericamente altas de supressão do eixo HPA com outras formulações tópicas de propionato de clobetasol.

Limitações de uso

O spray CLOBEX®, 0,05% não deve ser usado na face, axilas ou virilha. Spray CLOBEX®, 0,05% não deve ser usado se houver atrofia no local do tratamento. O spray CLOBEX®, 0,05% não deve ser usado no tratamento de rosácea ou dermatite perioral.

A espuma espectro é um corticosteróide indicado para o tratamento da psoríase em placas moderada a grave do couro cabeludo e da psoríase em placas leve a moderada de regiões não escalpadas do corpo, excluindo a face e as áreas intertriginosas em pacientes com 12 anos ou mais.

Spectro Ointment é indicado para tratamento a curto prazo de manifestações inflamatórias e pruríticas de dermatoses responsivas a corticosteróides moderadas a graves. O tratamento além de duas semanas consecutivas não é recomendado e a dose total não deve exceder 50 g por semana, devido ao potencial do medicamento para suprimir o eixo hipotálamo-hipófise-adrenal (HPA).

Este produto não é recomendado em pacientes pediátricos com menos de 12 anos de idade.

O spray CLOBEX®, 0,05%, é apenas para uso tópico, e não para uso oftalmológico, oral ou intravaginal.

Spray CLOBEX®, 0,05% deve ser pulverizado diretamente nas áreas afetadas da pele duas vezes ao dia e esfregado suavemente e completamente.

A dosagem total não deve exceder 50 g (59 mL ou 2 onças fluidas) por semana, devido ao potencial do medicamento para suprimir o eixo hipotálamo-hipófise-adrenal (HPA). Não use mais de 26 sprays por aplicação ou 52 sprays por dia.

Spray CLOBEX®, 0,05% contém um corticosteróide tópico; portanto, o tratamento deve ser limitado a 4 semanas. A terapia deve ser descontinuada quando o controle for alcançado. O tratamento além de 2 semanas deve ser limitado a lesões localizadas de psoríase em placas moderada a grave que não melhoraram suficientemente após as duas semanas iniciais de tratamento com o spray CLOBEX®, 0,05%. Se nenhuma melhora for observada dentro de duas semanas, pode ser necessária uma reavaliação do diagnóstico. Antes de prescrever por mais de 2 semanas, quaisquer benefícios adicionais da extensão do tratamento para 4 semanas devem ser ponderados em relação ao risco de supressão do eixo HPA.

O uso em pacientes pediátricos com menos de 18 anos não é recomendado devido ao potencial de supressão do eixo HPA.

A menos que seja dirigido pelo médico, o spray CLOBEX®, 0,05% não deve ser usado com curativos oclusivos.

Aplique uma fina camada de espuma Spectro nas áreas afetadas da pele duas vezes ao dia.

Spectro Foam é um corticosteróide tópico de alta potência; portanto, limite o tratamento para 2 semanas consecutivas. Os pacientes não devem usar mais de 50 gramas por semana ou mais de 21 capfuls por semana, devido ao potencial do medicamento para suprimir o eixo hipotálamo-hipófise-adrenal (HPA).

A terapia deve ser descontinuada quando o controle for alcançado.

A espuma Spectro não deve ser usada com curativos oclusivos, a menos que seja dirigido por um médico.

Espuma Espectro é apenas para uso tópico. Não é para uso oral, oftalmológico ou intravaginal.

Evite o contato com os olhos. Lave as mãos após cada aplicação.

Evite o uso no rosto, virilha ou axilas ou se houver atrofia da pele no local do tratamento.

Uma fina camada de Spectro Ointment deve ser aplicada com fricção suave na área da pele afetada duas vezes ao dia, uma vez pela manhã e outra à noite.

O Spectro Ointment é potente; portanto, o tratamento deve ser limitado a duas semanas consecutivas e quantidades superiores a 50 g por semana não devem ser usadas. Spectro Ointment não deve ser usado com curativos oclusivos.

Nenhum.

Espectro (propionato de clobetasol) A espuma é contra-indicada em pacientes hipersensíveis ao propionato de clobetasol, a outros corticosteróides ou a qualquer ingrediente desta preparação.

O Spectro Ointment está contra-indicado em pacientes hipersensíveis ao propionato de clobetasol, a outros corticosteróides ou a qualquer ingrediente nesta preparação.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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, CLOBEX® Spray, 0.05% demonstrated rates of suppression that were comparable after 2 and 4 weeks of twice-daily use (19% and 15-20%, 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 μg/dL 30-min post cosyntropin stimulation.

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.

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.

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.

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 CLOBEX® Spray, 0.05% should be discontinued until the infection has been adequately controlled.

Flammable Contents

CLOBEX® Spray, 0.05% is flammable; keep away from heat or flame.

Patient Counseling Information

Information for Patients

Patients using topical corticosteroids should receive the following information and instructions:

• This medication is to be used as directed by the physician and should not be used longer than the prescribed time period.
• This medication should not be used for any disorder other than that for which it was prescribed.
• Do not use other corticosteroid-containing products while using CLOBEX® Spray, 0.05% unless directed by your physician.
• The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.
• Patients should wash their hands after applying the medication.
• Patients should report any signs of local or systemic adverse reactions to the physician.
• Patients should inform their physicians that they are using CLOBEX® Spray, 0.05% if surgery is contemplated.
• If you go to another doctor for illness, injury or surgery, tell that doctor you are using CLOBEX® Spray, 0.05%.
• This medication is for external use only. It should not be used on the face, underarms, or groin area. Also avoid contact with the eyes and lips.
• As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.
• Patients should not use more than 50 g (59 mL or 2 fl.oz.) per week of CLOBEX® Spray, 0.05%.
• Do not use more than 26 sprays per application or 52 sprays per day.
• This medication is flammable; avoid heat, flame or smoking when applying this product.

Instructions to the Pharmacist:

1. Remove the spray pump from the wrapper
2. Remove and discard the cap from the bottle
3. Keeping the bottle vertical, insert the spray pump into the bottle and turn clockwise until well-fastened
4. Dispense the bottle with the spray pump inserted

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Clobetasol propionate was not carcinogenic to rats when topically applied for 2 years at concentrations up to 0.005% which corresponded to doses up to 11 μg/kg/day (ratio of animal dose to proposed human dose of 0.03 on a mg/m²/day basis). Clobetasol propionate at concentrations up to 0.001% did not increase the rate of formation of ultra violet light-induced skin tumors when topically applied to hairless mice 5 days per week for a period of 40 weeks.

Clobetasol propionate was negative in the in vitro mammalian chromosomal aberration test and in the in vivo mammalian erythrocyte micronucleus test

The effect of subcutaneously administered clobetasol propionate on fertility and general reproductive toxicity was studied in rats at doses of 0, 12.5, 25, and 50 μg/kg/day. Males were treated beginning 70 days before mating and females beginning 15 days before mating through day 7 of gestation. A dosage level of less than 12.5 μg/kg/day clobetasol propionate was considered to be the no-observed-effect-level (NOEL) for paternal and maternal general toxicity based on decreased weight gain and for male reproductive toxicity based on increased weights of the seminal vesicles. The female reproductive NOEL was 12.5 μg/kg/day (ratio of animal dose to proposed human dose of 0.03 on a mg/m²/day basis) based on reduction in the numbers of estrous cycles during the pre-cohabitation period and an increase in the number of nonviable embryos at higher doses.

Use In Specific Populations

Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Therefore, CLOBEX® Spray, 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.

Clobetasol propionate is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and the mouse.

Clobetasol propionate has greater teratogenic potential 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 μg/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 NOEL for clobetasol propionate was less than 12.5 μg/kg/day due to reduced body weight gain and feed consumption during the gestation period. The reproductive NOEL in the dams was 25 μg/kg/day (ratio of animal dose to proposed human dose of 0.07 on a mg/m²/day basis) based on prolonged delivery at a higher dose level. The no-observed-adverse-effect-level (NOAEL) for viability and growth in the offspring was 12.5 μg/kg/day (ratio of animal dose to proposed human dose of 0.03 on a mg/m²/day basis) 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.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, caution should be exercised when CLOBEX® Spray, 0.05% is administered to a nursing woman.

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 CLOBEX® Spray, 0.05% have not been established.

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.

Geriatric Use

Clinical studies of CLOBEX® 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.

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Effects On Endocrine System

Spectro Foam can cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or after withdrawal of treatment. Factors that predispose a patient to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test.

In a trial evaluating the effects of Spectro Foam on the HPA axis, 13 subjects applied Spectro Foam to at least 20% of involved body surface area for 14 days. HPA axis suppression was identified in 5 out of 13 subjects (38%).

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid.

Cushing’s syndrome and hyperglycemia may also occur due to the systemic effects of the topical corticosteroid. These complications are rare and generally occur after prolonged exposure to excessively large doses, especially of high-potency topical corticosteroids.

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios.

Ophthalmic Adverse Reactions

Use of topical corticosteroids, including Spectro Foam, 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.

Avoid contact of Spectro Foam with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

Allergic Contact Dermatitis

Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing.

Flammable Contents

Spectro Foam is flammable. Avoid fire, flame, or smoking during and immediately following application.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION and Instructions For Use)

Effects On Endocrine System

Spectro Foam may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including Spectro Foam, may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. Concomitant use of multiple corticosteroid-containing products may increase the total systemic exposure to topical corticosteroids. Patients should inform their physician(s) that they are using Spectro Foam if surgery is contemplated.

Ophthalmic Adverse Reactions

Advise patients to report any visual symptoms to their healthcare providers.

Local Adverse Reactions

Report any signs of local adverse reactions to the physician. Advise patients that local reactions and skin atrophy are more likely to occur with occlusive use or prolonged use.

Pregnancy

Advise pregnant women of the potential risk to a fetus and to use Spectro Foam on the smallest area of skin and for the shortest duration possible.

Lactation

Advise a woman to use Spectro Foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Spectro Foam directly to the nipple and areola to avoid direct infant exposure.

Important Administration Instructions

Inform patients of the following:

• Avoid use of Spectro Foam on the face, underarms, or groin areas unless directed by the physician.
• Do not occlude the treatment area with bandage or other covering, unless directed by the physician.
• Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, contact the physician.
• For proper dispensing of foam, hold the can upside down and depress the actuator. Dispensing directly onto hands is not recommended (unless the hands are the affected area), as the foam will begin to melt immediately upon contact with warm skin.
• Limit treatment to 2 consecutive weeks. Use no more than 50 grams of Spectro Foam per week, or more than 21 capfuls per week.
• Avoid use of Spectro Foam in the diaper area, as diapers or plastic pants may constitute occlusive dressing.
• The product is flammable; avoid heat, flame, and smoking when applying this product.
• Do not use other corticosteroid-containing products without first consulting with the physician.

Spectro is a registered trademark of Stiefel Laboratories, Inc., a GSK Company, exclusively licensed to the Mylan Companies.

For additional information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or visit www.Spectro.com.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Spectro Foam or clobetasol propionate.

In a 90-day repeat-dose toxicity study in rats, topical administration of clobetasol propionate foam at dose concentrations from 0.001% to 0.1% or from 0.03 to 0.3 mg/kg/day of clobetasol propionate resulted in a toxicity profile consistent with long-term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression, and opportunistic fungal and bacterial infections. A no observable adverse effect level could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk for carcinogenesis.

Clobetasol propionate was nonmutagenic in the Ames test, the mouse lymphoma test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test. In the in vivo mouse micronucleus test, a positive finding was observed at 24 hours, but not at 48 hours, following oral administration at a dose of 2,000 mg/kg.

Studies in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

Use In Specific Populations

Pregnancy

Risk Summary

There are no available data on Spectro Foam use in pregnant women to inform of a drug-associated risk for adverse developmental outcomes.

Published data report a significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. Advise pregnant women of the potential risk to a fetus and to use Spectro Foam on the smallest area of skin and for the shortest duration possible (see Data). In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits. No comparison of animal exposure with human exposure was computed.

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 background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Multiple observational studies found no significant associations between maternal use of topical corticosteroids of any potency and congenital malformations, preterm delivery, or fetal mortality. However, when the dispensed amount of potent or very potent topical corticosteroid exceeded 300 g during the entire pregnancy, use was associated with an increase in low birth weight infants [adjusted RR, 7.74 (95% CI, 1.49–40.11)]. In addition, a small cohort study, in which 28 sub-Saharan women using potent topical corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during pregnancy, noted a higher incidence of low birth weight infants in the exposed group. The majority of exposed subjects treated large areas of the body (a mean quantity of 60 g/month (range, 12–170g) over long periods of time.

Animal Data

Embryofetal development studies conducted with clobetasol propionate in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and malformations at all dose levels tested down to 0.03 mg/kg. Malformations seen included cleft palate and skeletal abnormalities.

Lactation

Risk Summary

There is no information regarding the presence of clobetasol propionate in breast milk or its effects on the breastfed infant or on milk production. Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. 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 Spectro Foam and any potential adverse effects on the breastfed infant from Spectro Foam or from the underlying maternal condition.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breast milk, use Spectro Foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Spectro Foam directly to the nipple and areola to avoid direct infant exposure.

Pediatric Use

Safety and effectiveness of Spectro Foam in patients younger than 12 years of age have not been established; therefore, use in children younger than 12 years is not recommended.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity when they are treated with topical drugs. They are, therefore, also at greater risk of adrenal insufficiency upon the use of topical corticosteroids.

Rare systemic toxicities such as Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients especially those with prolonged exposure to large doses of high potency topical corticosteroids.

Local adverse reactions including striae have also been reported with use of topical corticosteroids in pediatric patients.

Avoid use of Spectro Foam in the treatment of diaper dermatitis.

Geriatric Use

Clinical studies of Spectro Foam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.

WARNINGS

No information provided.

PRECAUTIONS

General

Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g per day. Systemic absorption of topical corticosteroids has resulted in reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

Conditions that augment systemic absorption include the application of more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid.

Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids.

Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity (See PRECAUTIONS: Pediatric Use).

If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.

In the presence of dermatologic infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

Certain areas of the body, such as the face, groin, and axillae, are more prone to atrophic changes than other areas of the body following treatment with corticosteroids. Frequent observation of the patient is important if these areas are to be treated.

As with other potent topical corticosteroids, Spectro Ointment should not be used in the treatment of rosacea and perioral dermatitis. Topical corticosteroids in general should not be used in the treatment of acne or as sole therapy in widespread plaque psoriasis.

Laboratory Tests

The following tests may be helpful in evaluating HPA axis suppression:

Urinary free cortisol test
ACTH stimulation test

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids.

Studies to determine mutagenicity with prednisolone have revealed negative results.

Pregnancy

Teratogenic Effects: Pregnancy Category C: The more potent corticosteroids have been shown to be teratogenic in animals after dermal application. Clobetasol propionate has not been tested for teratogenicity by this route; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and the mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.

There are no adequate and well-controlled studies of the teratogenic effects of topically applied corticosteroids, including clobetasol, in pregnant women. Therefore, clobetasol and other topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and they should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

Nursing Mothers

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are prescribed for a nursing woman.

Pediatric Use

Use of Spectro Ointment in pediatric patients under 12 years of age is not recommended.

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio.

HPA axis suppression, Cushing's syndrome, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Geriatric Use

Clinical studies of clobetasol propionate scalp application, 0.05% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious.

Experiência em ensaios clínicos

Como os ensaios clínicos são conduzidos em condições muito variadas, as taxas de reação adversa observadas nos ensaios clínicos de um medicamento não podem ser diretamente comparadas às taxas nos ensaios clínicos de outro medicamento e podem não refletir as taxas observadas na prática.

Em ensaios clínicos controlados com spray CLOBEX®, 0,05%, a reação adversa mais comum foi a queima no local da aplicação [40% dos indivíduos tratados com spray CLOBEX®, 0,05% e 47% dos indivíduos tratados com veículo em spray]. Outras reações adversas comumente relatadas para o spray CLOBEX®, 0,05% e veículo em spray, respectivamente, são observadas na Tabela 1.

Tabela 1: Reações adversas comumente recorrentes (≥ 1% de incidência)

A maioria das reações adversas locais foi classificada como leve a moderada e não é afetada por idade, raça ou sexo.

A absorção sistêmica de corticosteróides tópicos produziu supressão do eixo hipotálamo-hipófise-adrenal (HPA), manifestações da síndrome de Cushing, hiperglicemia e glucosúria em alguns pacientes.

Experiência pós-comercialização

Como essas reações são relatadas voluntariamente a partir de uma população de tamanho incerto, nem sempre é possível estimar com segurança sua frequência ou estabelecer uma relação causal com a exposição a medicamentos.

As seguintes reações adversas foram identificadas durante o uso pós-aprovação do spray CLOBEX®, 0,05%.

Pele:Queimação, prurido, eritema, dor, irritação, erupção cutânea, descamação, urticária e dermatite de contato.

As seguintes reações adversas são discutidas em mais detalhes em outras seções da rotulagem :

• Efeitos no sistema endócrino
• Reações adversas oftálmicas

Experiência em ensaios clínicos

Como os ensaios clínicos são conduzidos em condições muito variadas, as taxas de reação adversa observadas nos ensaios clínicos de um medicamento não podem ser diretamente comparadas às taxas nos ensaios clínicos de outro medicamento e podem não refletir as taxas observadas na prática clínica.

Em um ensaio clínico controlado envolvendo 188 indivíduos com psoríase do couro cabeludo, não foram relatadas reações adversas localizadas no couro cabeludo nos indivíduos tratados com espuma Spectro. Em 2 ensaios clínicos controlados com Spectro Foam em 360 indivíduos com psoríase de regiões não escalpadas, os eventos adversos localizados que ocorreram nos indivíduos tratados com Spectro Foam incluíram queima no local da aplicação (10%), secura no local da aplicação (<1%) e outras reações no local da aplicação (4%).

Em ensaios controlados maiores com outras formulações de propionato de clobetasol, as reações adversas locais mais frequentemente relatadas incluíram queimação, picada, irritação, prurido, eritema, foliculite, rachaduras e fissuras da pele, dormência dos dedos, atrofia da pele e telangiectasia (todos menos de 2%).

Experiência pós-comercialização

Como as reações adversas são relatadas voluntariamente de uma população de tamanho incerto, nem sempre é possível estimar com segurança sua frequência ou estabelecer uma relação causal com a exposição ao medicamento.

As reações adversas locais aos corticosteróides tópicos podem incluir: estrias, coceira, erupções acneiformes, hipopigmentação, dermatite perioral, dermatite alérgica de contato, infecção secundária, hipertricose e miliária.

As reações adversas oftálmicas podem incluir: catarata, glaucoma, aumento da pressão intra-ocular e coriorretinopatia serosa central.

O Spectro Ointment é geralmente bem tolerado quando usado por períodos de tratamento de duas semanas. As reações adversas mais frequentes relatadas para pomada de propionato de clobetasol foram locais e incluíram sensação de queimação, irritação e coceira. Estes ocorreram em aproximadamente 0,5% dos pacientes. Reações adversas menos frequentes foram picada, rachaduras, eritema, foliculite, dormência dos dedos, atrofia da pele e telangiectasia, que ocorreram em aproximadamente 0,3% dos pacientes.

As seguintes reações adversas locais são relatadas com pouca frequência quando corticosteróides tópicos são usados conforme recomendado. Essas reações estão listadas em uma ordem de ocorrência aproximadamente decrescente: queimação, coceira, irritação, secura, foliculite, hipertricose, erupções acneiformes, hipopigmentação, dermatite perioral, dermatite alérgica de contato, maceração da pele, infecção secundária, atrofia da pele, estrias e miliária. A absorção sistêmica de corticosteróides tópicos produziu supressão reversível do eixo HPA, manifestações da síndrome de Cushing, hiperglicemia e glucosúria em alguns pacientes. Em casos raros, acredita-se que o tratamento (ou retirada do tratamento) da psoríase com corticosteróides tenha exacerbado a doença ou provocado a forma pustular da doença, pelo que é recomendada uma cuidadosa supervisão do paciente.

O spray CLOBEX® aplicado topicamente, 0,05% pode ser absorvido em quantidade suficiente para produzir efeitos sistêmicos.

Espectro (propionato de clobetasol) aplicado topicamente A espuma pode ser absorvida em quantidades suficientes para produzir efeitos sistêmicos. Vejo PRECAUÇÕES.

O Spectro Ointment aplicado topicamente pode ser absorvido em quantidades suficientes para produzir efeitos sistêmicos (ver PRECAUÇÕES).

Ensaio Vasoconstritor

Spray CLOBEX®, 0,05% está na faixa super alta de potência, como demonstrado em um estudo vasoconstritor em indivíduos saudáveis quando comparado com outros corticosteróides tópicos. No entanto, escores semelhantes de branqueamento não implicam necessariamente equivalência terapêutica.

Supressão do Eixo Hipotalâmico-Pituitária-Adrenal (HPA)

O efeito do spray CLOBEX®, 0,05% na função do eixo hipotálamo-hipófise-adrenal (HPA) foi investigado em adultos em dois estudos. No primeiro estudo, pacientes com psoríase em placas cobrindo pelo menos 20% do corpo aplicaram o spray CLOBEX®, 0,05% duas vezes ao dia por até 4 semanas. 15% (2 em 13) dos pacientes apresentaram supressão adrenal após 4 semanas de uso com base no Teste de Estimulação de Cosyntropin. A supressão do laboratório foi transitória; todos os indivíduos voltaram ao normal após a interrupção do uso de drogas. No segundo estudo, pacientes com psoríase em placas cobrindo pelo menos 20% do corpo aplicaram o spray CLOBEX®, 0,05% duas vezes ao dia por 2 ou 4 semanas. 19% (4 em 21) dos pacientes tratados por 2 semanas e 20% (3 em 15) dos pacientes tratados por 4 semanas apresentaram supressão adrenal no final do tratamento com base no Teste de Estimulação de Cosintropina. A supressão do laboratório foi transitória; todos os indivíduos voltaram ao normal após a interrupção do uso de drogas. Nestes estudos, a supressão do eixo HPA foi definida como estimulação do nível sérico de cortisol ≤ 18 μg / dL 30 minutos após a cosyntropina (ACTH 1-24).

Num ensaio farmacocinético controlado, 5 de 13 indivíduos apresentaram supressão reversível das supra-renais a qualquer momento durante os 14 dias de terapia com Spectro Foam aplicada a pelo menos 20% da área da superfície corporal envolvida. Dos 13 indivíduos estudados, 1 de 9 com psoríase foi suprimida após 14 dias e todos os 4 indivíduos com dermatite atópica apresentaram níveis anormais de cortisol indicativos de supressão adrenal em algum momento após o início da terapia com Spectro Foam (veja a Tabela 1 abaixo).

Tabela 1: Assuntos com supressão reversível do eixo HPA a qualquer momento durante o tratamento

A extensão da absorção percutânea de corticosteróides tópicos é determinada por muitos fatores, incluindo o veículo, a integridade da barreira epidérmica e a oclusão.

Os corticosteróides tópicos podem ser absorvidos da pele intacta normal. A inflamação e outros processos de doenças na pele podem aumentar a absorção percutânea.

Não há dados humanos sobre a distribuição de corticosteróides nos órgãos do corpo após aplicação tópica. No entanto, uma vez absorvidos pela pele, os corticosteróides tópicos são manipulados por vias metabólicas semelhantes aos corticosteróides administrados sistemicamente. Eles são metabolizados, principalmente no fígado, e são excretados pelos rins. Além disso, alguns corticosteróides e seus metabólitos também são excretados na bílis.

Os corticosteróides tópicos podem ser absorvidos pela pele saudável intacta. A extensão da absorção percutânea de corticosteróides tópicos é determinada por muitos fatores, incluindo a formulação do produto e a integridade da barreira epidérmica. Oclusão, inflamação e / ou outros processos de doenças na pele também podem aumentar a absorção percutânea. Uma vez absorvidos pela pele, os corticosteróides tópicos são metabolizados, principalmente no fígado, e depois são excretados pelos rins. Alguns corticosteróides e seus metabólitos também são excretados na bílis.