Clobex Shampoo 0.050 %

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. Due to the fact that circulating levels are well below the level of detection, the use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary. 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.

Clobex (clobetasol propionate) is a super-high potency topical corticosteroid. Like other topical corticosteroids, Clobex Shampoo (clobetasol propionate shampoo, 0.05%) 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.

Clinical studies of Clobetasol Propionate Shampoo, 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, 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.

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

Long term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate. Clobetasol propionate did not produce any increase in chromosomal aberrations in Chinese hamster ovary cells in vitro in the presence or absence of metabolic activation. Clobetasol propionate was also negative in the micronucleus test in mice after oral administration. Studies of the effect of Clobex Shampoo on fertility have not been performed.

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 Shampoo is administered to a nursing woman.

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis 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.

The effect of Clobex Shampoo (clobetasol propionate, 0.05%) on HPA axis suppression was evaluated in one study in adolescents 12 to 17 years of age. In this study, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with Clobex Shampoo applied once daily.

Conditions which increase systemic absorption include the application of the more potent corticosteroids, 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 HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol 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 topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

If irritation develops, Clobex Shampoo (clobetasol propionate shampoo, 0.05%) should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation, as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

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 Shampoo should be discontinued until the infection has been adequately controlled.

Although Clobex Shampoo is intended for the topical treatment of moderate to severe scalp psoriasis, it should be noted that 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. Clobex Shampoo should not be used on the groin or axillae. Avoid any contact of the drug product with the facial skin, eyes and lips. In case of contact, rinse thoroughly with water all parts of the body that came in contact with the shampoo.

Suitable precautions should be taken when using topical corticosteroids in patients with stasis dermatitis and other skin diseases with impaired circulation.

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 in laboratory animals. A teratogenicity study of clobetasol propionate in rats using the dermal route resulted in dose related material toxicity and fetal effects from 0.05 to 0.5 mg/kg/day. These doses are approximately 0.1 to 1.0 times, respectively, the maximum human topical dose of clobetasol propionate from Clobex Shampoo. Abnormalities seen included low fetal weights, umbilical herniation, cleft palate, reduced skeletal ossification, and other skeletal abnormalities. Clobetasol propionate administered to rats subcutaneously at a dose of 0.1 mg/kg from day 17 of gestation to day 21 postpartum was associated with prolongation of gestation, decreased number of offspring, increased perinatal mortality of offspring, delayed eye opening and delayed hair appearance in surviving offspring. Some increase in offspring perinatal mortality was also observed at a dose of 0.05 mg/kg. Doses of 0.05 and 0.1 mg/kg are approximately 0.1 and 0.2 fold the maximum human topical dose of clobetasol propionate from Clobex Shampoo.

There have been no adequate and well controlled studies in pregnant women. Clobex Shampoo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Safety and effectiveness of Clobex Shampoo 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 of 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.

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

1. This medication is to be used as directed by the physician and should not be used longer than the prescribed time period. Patients should not use more than 50 g (50 mL) per week of clobetasol propionate shampoo 0.05%. It is for external use only. Avoid contact with the eyes.

   
   

2. Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.

   
   

3. This medication should not be used for any disorder other than that for which it was prescribed.

   
   

4. The scalp area should not be covered while the medication is on the scalp (e.g., shower cap, bathing cap) so as to be occlusive unless directed by the physician.

   
   

5. Patients should report to their physician any signs of local adverse reactions.

   
   

6. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician.

   
   

7. Patients should wash their hands after applying the medication.

   
   

8. Patients should inform their physician(s) that they are using Clobex Shampoo if surgery is contemplated.

   
   

For additional information, see Information for the Patient.

In the event of overdose, systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. (See Precautions.)