Topically applied CLOBEX® Spray, 0.05% can be absorbed in sufficient amount to produce systemic effects.
Topically applied Clarelux (clobetasol propionate) Foam can be absorbed in sufficient amounts to produce systemic effects. See PRECAUTIONS.
Topically applied Clarelux Ointment can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In controlled, clinical trials with CLOBEX® Spray, 0.05%, the most common adverse reaction was burning at the site of application [40% of subjects treated with CLOBEX® Spray, 0.05% and 47% of subjects treated with Spray Vehicle]. Other commonly reported adverse reactions for CLOBEX® Spray, 0.05% and Spray Vehicle, respectively, are noted in Table 1.
Table 1 : Commonly Occurring Adverse Reactions ( ≥ 1% Incidence)
| Adverse Reaction | Clobetasol Propionate 0.05% Spray (N=120) | Vehicle Spray (N=120) |
| System Organ Class | ||
| General disorders and administration site conditions | 50 (42%) | 56 (47%) |
| Application site burning | 48 (40%) | 56 (47%) |
| Application site dryness | 2 (2%) | 0 (0%) |
| Application site irritation | 1 (1%) | 0 (0%) |
| Application site pain | 1 (1%) | 2 (2%) |
| Application site pigmentation changes | 1 (1%) | 0 (0%) |
| Application site pruritus | 4 (3%) | 3 (3%) |
| Infections and infestations | 17 (14%) | 12 (10%) |
| Nasopharyngitis | 6 (5%) | 3 (3%) |
| Pharyngitis streptococcal | 1 (1%) | 0 (0%) |
| Upper respiratory tract infection | 10 (8%) | 2 (2%) |
| Skin and subcutaneous tissue disorders | 4 (3%) | 2 (2%) |
| Eczema asteatotic | 2 (2%) | 0 (0%) |
Most local adverse reactions were rated as mild to moderate and they are not affected by age, race or gender.
Systemic absorption of topical corticosteroids has produced hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.
Postmarketing ExperienceBecause these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been identified during post-approval use of CLOBEX® Spray, 0.05%.
Skin:Burning, pruritus, erythema, pain, irritation, rash, peeling, urticaria, and contact dermatitis.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In a controlled clinical trial involving 188 subjects with psoriasis of the scalp, there were no localized scalp adverse reactions reported in the subjects treated with Clarelux Foam. In 2 controlled clinical trials with Clarelux Foam in 360 subjects with psoriasis of non-scalp regions, localized adverse events that occurred in the subjects treated with Clarelux Foam included application site burning (10%), application site dryness (<1%), and other application site reactions (4%).
In larger controlled trials with other clobetasol propionate formulations, the most frequently reported local adverse reactions have included burning, stinging, irritation, pruritus, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, skin atrophy, and telangiectasia (all less than 2%).
Postmarketing ExperienceBecause adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Local adverse reactions to topical corticosteroids may include: striae, itching, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria.
Ophthalmic adverse reactions may include: cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy.
Clarelux Ointment is generally well tolerated when used for two-week treatment periods. The most frequent adverse reactions reported for clobetasol propionate ointment have been local and have included burning sensation, irritation, and itching. These occured in approximately 0.5% of the patients. Less frequent adverse reactions were stinging, cracking, erythema, folliculitis, numbness of fingers, skin atrophy, and telangiectasia, which occurred in approximately 0.3% of the patients.
The following local adverse reactions are reported infrequently when topical corticosteroids are used as recommended. These reactions are listed in an approximately decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria. Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. In rare instances, treatment (or withdrawal of treatment) of psoriasis with corticosteroids is thought to have exacerbated the disease or provoked the pustular form of the disease, so careful patient supervision is recommended.
CLOBEX® Spray, 0.05% is in the super-high range of potency as demonstrated in a vasoconstrictor study in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.
Hypothalamic-Pituitary-Adrenal (HPA) Axis SuppressionThe effect of CLOBEX® Spray, 0.05% on hypothalamic-pituitary-adrenal (HPA) axis function was investigated in adults in two studies. In the first study, patients with plaque psoriasis covering at least 20% of there body applied CLOBEX® Spray, 0.05% twice daily for up to 4 weeks. 15% (2 out of 13) of patients displayed adrenal suppression after 4 weeks of use based on the Cosyntropin Stimulation Test. The laboratory suppression was transient; all subjects returned to normal after cessation of drug use. In the second study, patients with plaque psoriasis covering at least 20% of their body applied CLOBEX® Spray, 0.05% twice daily for either 2 or 4 weeks. 19% (4 out of 21) of patients treated for 2 weeks and 20% (3 out of 15) of patients treated for 4 weeks displayed adrenal suppression at the end of treatment based on the Cosyntropin Stimulation Test. The laboratory suppression was transient; all subjects returned to normal after cessation of drug use. In these studies, HPA axis suppression was defined as serum cortisol level ≤ 18 μg/dL 30-min post cosyntropin (ACTH 1-24) stimulation.
In a controlled pharmacokinetic trial, 5 of 13 subjects experienced reversible suppression of the adrenals at any time during the 14 days of therapy with Clarelux Foam applied to at least 20% of involved body surface area. Of the 13 subjects studied, 1 of 9 with psoriasis was suppressed after 14 days and all 4 of the subjects with atopic dermatitis had abnormal cortisol levels indicative of adrenal suppression at some time after starting therapy with Clarelux Foam (See Table 1 below).
Table 1: Subjects With Reversible HPA Axis Suppression at Any Time During Treatment
| Dermatosis | Clarelux Foam |
| Psoriasis | 1 of 9 |
| Atopic Dermatitisa | 4 of 4 |
| a Clarelux Foam is not indicated for non-scalp atopic dermatitis, as the safety and efficacy of Clarelux Foam in non-scalp atopic dermatitis has not been established. Use in children under 12 years of age is not recommended. |
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion.
Topical corticosteroids can be absorbed from normal intact skin. Inflammation and other disease processes in the skin may increase percutaneous absorption.
There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through metabolic pathways similar to systemically administered corticosteroids. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.
Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation and the integrity of the epidermal barrier. Occlusion, inflammation, and/or other disease processes in the skin may also increase percutaneous absorption. Once absorbed through the skin, topical corticosteroids are metabolized, primarily in the liver, and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.
