Clobex Spray 0.050 %

Interactions with herbal products have not been established.

Interactions with food have not been established. However, given the topical route of administration, such interactions seem unlikely.

Interactions with other drugs have not been established.

Interactions with laboratory tests have not been established.

To date, there have not been any documented interactions with Clobex Spray (clobetasol propionate solution), 0.05%.

treatment should be limited to adult patients, aged 18 years of age and older

Clobex Spray (clobetasol propionate solution), 0.05% should be applied to the affected skin areas twice daily and rubbed in gently and completely.

Treatment with Clobex Spray, 0.05% should be limited to four weeks. Treatment beyond two weeks should be limited to localized lesions of moderate to severe plaque psoriasis that have not sufficiently improved after the initial two weeks of treatment with Clobex Spray, 0.05%.

Total dosage of the product should not exceed 50 mL per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Therapy should be discontinued when control has been achieved. If no improvement is seen within two weeks, reassessment of diagnosis may be necessary.

Clobex Spray (clobetasol propionate solution), 0.05% is not indicated for long-term use. Patients should be instructed to use Clobex Spray for the minimum amount of time necessary. Intermittent use has not been studied.

Clobex Spray, 0.05% should not be used with occlusive dressings.

Clobex Spray, 0.05% should be applied to the affected skin areas twice daily and rubbed in gently and completely.

In the event of a missed dose, Clobex Spray, 0.05% should be applied as soon as possible after the missed dose is remembered. If this is close to the scheduled application time for the next dose, the subject should wait and apply the next scheduled dose. The usual schedule should be resumed thereafter.

The most common adverse reaction reported with Clobex Spray (clobetasol propionate solution), 0.05% is burning at the application site. Other common adverse reactions are local site effects as well, including pruritus, dryness, pain, hyperpigmentation around resolving plaque, irritation, and atrophy. Most local adverse events were rated as mild to moderate and were not affected by age, race or gender.

One serious, unexpected adverse event, designated as possibly related to treatment by the clinical investigator, was reported during the clinical trial programme with Clobex Spray, 0.05%. This severe event was reported as paranoid delusions in a subject with a seven-year history of intermittent methamphetamine use. Although the event was thought to be related to methamphetamine use by the treating psychiatrist, the possibility of a treatment relationship to clobetasol propionate solution (i.e., spray) could not be absolutely ruled out by the investigator.

Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

The following additional local adverse reactions have been reported with topical corticosteroids in general, and they may occur more frequently with the use of occlusive dressings, use over a prolonged period of time, or use over large surface areas, especially with higher potency corticosteroids, including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence: irritation, dryness, itching, burning, local irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, skin atrophy, atrophy of subcutaneous tissues, telangiectasia, hypertrichosis, change in pigmentation, secondary infection, striae and miliaria. If applied to the face, acne rosacea or perioral dermatitis can occur. When occlusive dressings are used, pustules, milaria, folliculitis and pyoderma may occur. In rare instances, treatment of psoriasis with systemic or very potent topical corticosteroids (or their withdrawal) is thought to have provoked the pustular form of the disease.

One subject treated for four weeks with Clobex Spray 0.05% experienced an elevated WBC, which was designated by the investigator as possibly related to treatment.

Treatment Related Adverse Events (At Least Possibly Related) Occurring at a Frequency of ≥1% of Subjects in at Least One Group (Clinical Studies TI01-01008 and TI01-01010 Combined)

No data are available.

Limited data are available. See Warnings and Precautions.

Clinical studies of Clobex Spray, 0.05%, did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be made with caution reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Use in those under 18 years of age is not recommended.

Clobex Spray (clobetasol propionate solution), 0.05% should not be used under occlusive dressing, over extensive areas, or on the face, axillae, or scrotum, as sufficient absorption may occur to give rise to adrenal suppression and other systemic effects.

In the presence of fungal infections, an appropriate antifungal treatment should be instituted and Clobex Spray, 0.05% should be discontinued until the fungal infection is cured. In the presence of a bacterial infection, an appropriate antibacterial agent should be instituted. If a favorable response does not occur promptly, Clobex Spray, 0.05% should be discontinued until the bacterial infection is adequately controlled.

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

• ACTH stimulation test

  
  

• A.M. plasma cortisol test

  
  

• Urinary free cortisol test

Systemic absorption of topical corticosteroids has caused reversible adrenal suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.

Conditions which increase systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of adrenal suppression (see Monitoring and Laboratory Tests). If adrenal 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 upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids. For information on systemic supplementation, see the Prescribing Information for those products.

Two studies were conducted to evaluate the effect of twice daily applications of Clobex Spray, 0.05% on HPA axis function in adults with plaque psoriasis covering at least 20% of their body. Study duration was two or four weeks. In the first study four of 14 (29%) patients displayed adrenal suppression after four weeks of use. In the second study, four of 19 (21%) of patients in the two week treatment group and four of 17 (24%) of patients in the four week treatment group displayed adrenal suppression. Suppression was transient, and all patients had returned to normal within 15-16 days of therapy cessation.

Safety and effectiveness of Clobex Spray, 0.05% have been established in patients 18 years and older. Insufficient data have been obtained in patients under the age of 18 years. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults for HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal 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. Therefore, use is not recommended in patients under the age of 18 years.

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 an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

If irritation develops, Clobex Spray, 0.05% should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by a failure to heal rather than by noting a clinical exacerbation, as is the case with most products not containing a corticosteroid.

Clobex Spray, 0.05% should not be used on plaques close to the eye because of the risk of increased intraocular pressure, glaucoma, and cataracts.

There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobex Spray, 0.05% should be used during pregnancy only if its benefit justifies the potential risk to the fetus. The extent of exposure during the clinical trials with Clobex Spray, 0.05% was very limited (one case).

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 human milk. Because many drugs are excreted in human milk, caution should be exercised when Clobex Spray, 0.05% is administered to a nursing woman.

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin while inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids, including clobetasol propionate and its metabolites, are also excreted in the bile.

Clobetasol propionate is a super-high potency topical corticosteroid. Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A₂ inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A₂.

The vasoconstriction capacity of Clobex Spray (clobetasol propionate solution), 0.05% is comparable to that of cream formulations of clobetasol propionate and superior to that of amcinonide cream, 0.1%.