Dermexane

Indication

Le spray CLOBEX®, 0,05% est une formulation corticostéroïde topique très puissante indiquée pour le traitement du psoriasis en plaques modéré à sévère affectant jusqu'à 20% de la surface corporelle (BSA) chez les patients âgés de 18 ans ou plus. La posologie totale ne doit pas dépasser 50 g (59 ml ou 2 fl. oz.) par semaine. N'utilisez pas plus de 26 pulvérisations par application ou 52 pulvérisations par jour. Le traitement doit être limité à 4 semaines consécutives.

Les patients doivent être informés de l'utilisation du spray CLOBEX®, à 0,05% pendant le temps minimum nécessaire pour obtenir les résultats souhaités. L'utilisation chez les patients de moins de 18 ans n'est pas recommandée car la sécurité n'a pas été établie et parce que des taux numériquement élevés de suppression de l'axe HPA ont été observés avec d'autres formulations topiques propionate de clobétasol.

Limitations d'utilisation

CLOBEX® Spray, 0,05% ne doit pas être utilisé sur le visage, les axilles ou l'aine. CLOBEX® Spray, 0,05% ne doit pas être utilisé en cas d'atrophie au site de traitement. CLOBEX® Spray, 0,05% ne doit pas être utilisé dans le traitement de la rosacée ou de la dermatite périorale.

La mousse de dermexane est un corticostéroïde indiqué pour le traitement du psoriasis en plaques modéré à sévère du cuir chevelu et du psoriasis en plaques léger à modéré des régions non scalp du corps, à l'exclusion du visage et des zones intertriginieuses chez les patients de 12 ans et plus.

La pommade au dermexane est indiquée pour le traitement à court terme des manifestations inflammatoires et prurigineuses des dermatoses sensibles aux corticostéroïdes modérées à sévères. Le traitement au-delà de deux semaines consécutives n'est pas recommandé et la posologie totale ne doit pas dépasser 50 g par semaine en raison du potentiel du médicament à supprimer l'axe hypothalamicpituitaire-adrénal (HPA).

Ce produit n'est pas recommandé chez les patients pédiatriques de moins de 12 ans.

CLOBEX® Spray, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use.

CLOBEX® Spray, 0.05% should be sprayed directly onto the affected skin areas twice daily and rubbed in gently and completely.

The total dosage should not exceed 50 g (59 mL or 2 fluid ounces) per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Do not use more than 26 sprays per application or 52 sprays per day.

CLOBEX® Spray, 0.05% contains a topical corticosteroid; therefore treatment should be limited to 4 weeks. Therapy should be discontinued when control has been achieved. Treatment beyond 2 weeks should be limited to localized lesions of moderate to severe plaque psoriasis that have not sufficiently improved after the initial 2 weeks of treatment with CLOBEX® Spray, 0.05%. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Before prescribing for more than 2 weeks, any additional benefits of extending treatment to 4 weeks should be weighed against the risk of HPA axis suppression.

Use in pediatric patients younger than 18 years is not recommended because of the potential for HPA axis suppression.

Unless directed by physician, CLOBEX® Spray, 0.05% should not be used with occlusive dressings.

Apply a thin layer of Dermexane Foam to the affected skin areas twice daily.

Dermexane Foam is a super-high-potency topical corticosteroid; therefore, limit treatment to 2 consecutive weeks. Patients should not use greater than 50 grams per week or more than 21 capfuls per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis.

Therapy should be discontinued when control is achieved.

Dermexane Foam should not be used with occlusive dressings unless directed by a physician.

Dermexane Foam is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

Avoid contact with eyes. Wash hands after each application.

Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site.

A thin layer of Dermexane Ointment should be applied with gentle rubbing to the affected skin area twice daily, once in the morning and once at night.

Dermexane Ointment is potent; therefore, treatment must be limited to two consecutive weeks, and amounts greater than 50 g per week should not be used. Dermexane Ointment is not to be used with occlusive dressings.

None.

Dermexane (clobetasol propionate) Foam is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

Dermexane Ointment is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

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

Dermexane 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 Dermexane Foam on the HPA axis, 13 subjects applied Dermexane 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 Dermexane 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 Dermexane 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

Dermexane 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

Dermexane Foam may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including Dermexane 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 Dermexane 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 Dermexane Foam on the smallest area of skin and for the shortest duration possible.

Lactation

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

Important Administration Instructions

Inform patients of the following:

• Avoid use of Dermexane 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 Dermexane Foam per week, or more than 21 capfuls per week.
• Avoid use of Dermexane 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.

Dermexane 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.Dermexane.com.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Dermexane 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 Dermexane 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 Dermexane 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 Dermexane Foam and any potential adverse effects on the breastfed infant from Dermexane Foam or from the underlying maternal condition.

Clinical Considerations

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

Pediatric Use

Safety and effectiveness of Dermexane 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 Dermexane Foam in the treatment of diaper dermatitis.

Geriatric Use

Clinical studies of Dermexane 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, Dermexane 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 Dermexane 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.

Expérience des essais cliniques

Étant donné que les essais cliniques sont menés dans des conditions très variables, les taux d'effets indésirables observés dans les essais cliniques d'un médicament ne peuvent pas être directement comparés aux taux dans les essais cliniques d'un autre médicament et peuvent ne pas refléter les taux observés dans la pratique.

Dans les essais cliniques contrôlés avec CLOBEX® Spray, 0,05%, l'effet indésirable le plus courant brûlait au site d'application [40% des sujets traités avec CLOBEX® Spray, 0,05% et 47% des sujets traités avec Spray Vehicle]. Les autres effets indésirables fréquemment rapportés pour le pulvérisateur CLOBEX®, 0,05% et le véhicule pulvérisateur, respectivement, sont indiqués dans le tableau 1.

Tableau 1: Effets indésirables fréquents (≥ 1% d'incidence)

La plupart des effets indésirables locaux ont été jugés légers à modérés et ne sont pas affectés par l'âge, la race ou le sexe.

L'absorption systémique des corticostéroïdes topiques a produit une suppression de l'axe hypothalamo-hypophyse-adrénal (HPA), des manifestations du syndrome de Cushing, une hyperglycémie et une glucosurie chez certains patients.

Expérience post-commercialisation

Étant donné que ces réactions sont rapportées volontairement à partir d'une population de taille incertaine, il n'est pas toujours possible d'estimer de manière fiable leur fréquence ou d'établir une relation causale avec l'exposition au médicament.

Les effets indésirables suivants ont été identifiés lors de l'utilisation post-approbation du spray CLOBEX®, 0,05%.

Peau:Brûlure, prurit, érythème, douleur, irritation, éruption cutanée, pelage, urticaire et dermatite de contact.

Les effets indésirables suivants sont discutés plus en détail dans d'autres sections de l'étiquetage:

• Effets sur le système endocrinien
• Effets indésirables ophtalmiques

Expérience des essais cliniques

Étant donné que les essais cliniques sont menés dans des conditions très variables, les taux d'effets indésirables observés dans les essais cliniques d'un médicament ne peuvent pas être directement comparés aux taux dans les essais cliniques d'un autre médicament et peuvent ne pas refléter les taux observés dans la pratique clinique.

Dans un essai clinique contrôlé portant sur 188 sujets atteints de psoriasis du cuir chevelu, aucun effet indésirable localisé du cuir chevelu n'a été signalé chez les sujets traités par la mousse de dermexane. Dans 2 essais cliniques contrôlés avec de la mousse de dermexane chez 360 sujets atteints de psoriasis de régions non scalp, les événements indésirables localisés survenus chez les sujets traités par la mousse de dermexane comprenaient la combustion au site d'application (10%), la sécheresse au site d'application (<1%) et d'autres réactions au site d'application (4%).

Dans les essais contrôlés plus importants avec d'autres formulations de propionate de clobétasol, les effets indésirables locaux les plus fréquemment rapportés ont inclus des brûlures, des picotements, une irritation, un prurit, un érythème, une folliculite, des fissures et des fissures cutanées, un engourdissement des doigts, une atrophie cutanée et une télangiectasie (tous moins de 2%).

Expérience post-commercialisation

Étant donné que les effets indésirables sont signalés volontairement par une population de taille incertaine, il n'est pas toujours possible d'estimer de manière fiable leur fréquence ou d'établir une relation causale avec l'exposition au médicament.

Les effets indésirables locaux des corticostéroïdes topiques peuvent inclure: stries, démangeaisons, éruptions acnéiformes, hypopigmentation, dermatite périorale, dermatite de contact allergique, infection secondaire, hypertrichose et miliaire.

Les effets indésirables ophtalmiques peuvent inclure: cataractes, glaucome, augmentation de la pression intraoculaire et choriorétinopathie séreuse centrale.

La pommade au dermexane est généralement bien tolérée lorsqu'elle est utilisée pendant des périodes de traitement de deux semaines. Les effets indésirables les plus fréquemment rapportés pour la pommade au propionate de clobétasol ont été locaux et ont inclus une sensation de brûlure, une irritation et des démangeaisons. Ceux-ci se sont produits chez environ 0,5% des patients. Les effets indésirables moins fréquents étaient des picotements, des fissures, des érythèmes, des folliculiites, un engourdissement des doigts, une atrophie cutanée et une télangiectasie, survenus chez environ 0,3% des patients.

Les effets indésirables locaux suivants sont rarement rapportés lorsque des corticostéroïdes topiques sont utilisés comme recommandé. Ces réactions sont répertoriées dans un ordre d'occurrence approximativement décroissant: brûlure, démangeaisons, irritation, sécheresse, folliculite, hypertrichose, éruptions acnéiformes, hypopigmentation, dermatite périorale, dermatite de contact allergique, macération de la peau, infection secondaire, atrophie cutanée, stries et la miliaria. L'absorption systémique des corticostéroïdes topiques a produit une suppression réversible de l'axe HPA, des manifestations du syndrome de Cushing, de l'hyperglycémie et de la glucosurie chez certains patients. Dans de rares cas, le traitement (ou le retrait du traitement) du psoriasis avec des corticostéroïdes aurait exacerbé la maladie ou provoqué la forme pustuleuse de la maladie, une surveillance attentive du patient est donc recommandée.

Spray CLOBEX® appliqué par voie topique, 0,05% peut être absorbé en quantité suffisante pour produire des effets systémiques.

La mousse de dermexane (propionate de clobétasol) appliquée par voie topique peut être absorbée en quantités suffisantes pour produire des effets systémiques. Voir PRÉCAUTIONS.

La pommade au dermexane appliquée par voie topique peut être absorbée en quantités suffisantes pour produire des effets systémiques (voir PRÉCAUTIONS).

Dosage Vasoconstricteur

Le spray CLOBEX®, 0,05% est dans la gamme de puissance ultra-élevée, comme démontré dans une étude vasoconstricteur chez des sujets sains par rapport à d'autres corticostéroïdes topiques. Cependant, des scores blanchissants similaires n'impliquent pas nécessairement une équivalence thérapeutique.

Suppression de l'axe hypothalamo-pituitaire-adrénal (HPA)

L'effet du spray CLOBEX®, 0,05% sur la fonction d'axe hypothalamo-hypophyse-adrénal (HPA) a été étudié chez l'adulte dans deux études. Dans la première étude, des patients atteints de psoriasis en plaques couvrant au moins 20% de leur corps ont appliqué le spray CLOBEX®, 0,05% deux fois par jour pendant 4 semaines maximum. 15% (2 sur 13) des patients ont présenté une suppression surrénale après 4 semaines d'utilisation sur la base du test de stimulation de la cosyntropine. La suppression en laboratoire était transitoire; tous les sujets sont revenus à la normale après l'arrêt de la consommation de drogues. Dans la deuxième étude, les patients atteints de psoriasis en plaques couvrant au moins 20% de leur corps ont appliqué le spray CLOBEX®, 0,05% deux fois par jour pendant 2 ou 4 semaines. 19% (4 sur 21) des patients traités pendant 2 semaines et 20% (3 sur 15) des patients traités pendant 4 semaines ont présenté une suppression surrénale à la fin du traitement sur la base du test de stimulation de la cosyntropine. La suppression en laboratoire était transitoire; tous les sujets sont revenus à la normale après l'arrêt de la consommation de drogues. Dans ces études, la suppression de l'axe HPA a été définie comme un taux de cortisol sérique ≤ 18 μg / dL 30 minutes après la stimulation par cosyntropine (ACTH 1-24).

Dans un essai pharmacocinétique contrôlé, 5 des 13 sujets ont connu une suppression réversible des glandes surrénales à tout moment au cours des 14 jours de traitement par la mousse de dermexane appliquée à au moins 20% de la surface corporelle impliquée. Sur les 13 sujets étudiés, 1 sur 9 atteints de psoriasis a été supprimé après 14 jours et les 4 sujets atteints de dermatite atopique avaient des taux de cortisol anormaux indiquant une suppression surrénale à un moment donné après le début du traitement par la mousse de dermexane (voir tableau 1 ci-dessous).

Tableau 1: Sujets présentant une suppression réversible de l'axe HPA à tout moment pendant le traitement

L'ampleur de l'absorption percutanée des corticostéroïdes topiques est déterminée par de nombreux facteurs, notamment le véhicule, l'intégrité de la barrière épidermique et l'occlusion.

Les corticostéroïdes topiques peuvent être absorbés par une peau intacte normale. L'inflammation et d'autres processus pathologiques dans la peau peuvent augmenter l'absorption percutanée.

Il n'y a pas de données humaines concernant la distribution de corticostéroïdes aux organes du corps après application topique. Néanmoins, une fois absorbés par la peau, les corticostéroïdes topiques sont manipulés par des voies métaboliques similaires aux corticostéroïdes administrés par voie systémique. Ils sont métabolisés, principalement dans le foie, puis excrétés par les reins. De plus, certains corticostéroïdes et leurs métabolites sont également excrétés dans la bile.

Les corticostéroïdes topiques peuvent être absorbés par une peau saine intacte. L'ampleur de l'absorption percutanée des corticostéroïdes topiques est déterminée par de nombreux facteurs, notamment la formulation du produit et l'intégrité de la barrière épidermique. L'occlusion, l'inflammation et / ou d'autres processus pathologiques dans la peau peuvent également augmenter l'absorption percutanée. Une fois absorbés par la peau, les corticostéroïdes topiques sont métabolisés, principalement dans le foie, puis excrétés par les reins. Certains corticostéroïdes et leurs métabolites sont également excrétés dans la bile.