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Siliq is intended for patients who are candidates for systemic therapy "...
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 [see CLINICAL PHARMACOLOGY].
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.
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]
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.
CLOBEX® Spray, 0.05% is flammable; keep away from heat or flame.
Patient Counseling Information
[See FDA-approved patient labeling (PATIENT 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:
- Remove the spray pump from the wrapper
- Remove and discard the cap from the bottle
- Keeping the bottle vertical, insert the spray pump into the bottle and turn clockwise until well-fastened
- Dispense the bottle with the spray pump inserted
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
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.
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.
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 [see WARNINGS AND PRECAUTIONS].
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.
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.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 9/14/2012
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