CLOBEX
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clobetasol propionate shampoo
Galderma Laboratories, L.P.
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| FULL PRESCRIBING INFORMATION: CONTENTS* | |
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
Clobex Shampoo is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe forms of scalp psoriasis in patients 18 years of age and older. Treatment should be limited to 4 consecutive weeks of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. There were insufficient numbers of non-Caucasian patients to determine whether they responded differently than Caucasian patients with regards to efficacy and safety.
2 DOSAGE AND ADMINISTRATION
Clobex Shampoo should be applied onto dry (not wet) scalp once a day in a thin film to the affected areas only, and left in place for 15 minutes before lathering and rinsing.
Move the hair away from the scalp so that one of the affected areas is exposed. Position the bottle over the lesion. Apply a small amount of the shampoo directly onto the lesion, letting the product naturally flow from the bottle (gently squeeze the bottle), avoiding any contact of the product with the facial skin, eyes or lips. In case of contact, rinse thoroughly with water. Spread the product so that the entire lesion is covered with a thin uniform film. Massage gently into the lesion and repeat for additional lesion(s). Wash your hands after applying Clobex Shampoo.
Leave the shampoo in place for 15 minutes, then add water, lather and rinse thoroughly all parts of the scalp and body that came in contact with the shampoo (e.g., hands, face, neck and shoulders). Avoid contact with eyes and lips. Minimize contact to non-affected areas of the body. Although no additional shampoo is necessary to cleanse your hair, you may use a non-medicated shampoo if desired. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week. Clobex Shampoo should not be used with occlusive dressings unless directed by a physician.
3 DOSAGE FORMS AND STRENGTHS
Shampoo: 0.05%
4 CONTRAINDICATIONS
Use of Clobex Shampoo is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.
5 WARNINGS AND PRECAUTIONS
HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS FUNCTION
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 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 corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings or use on occluded areas. 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. 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.
The effect of Clobex Shampoo 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 for 15 minutes to a dry scalp before lathering and rinsing.
If irritation develops, Clobex Shampoo 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 face, groin or axillae. Avoid any contact of the drug product with the eyes and lips. In case of contact, rinse thoroughly with water all parts of the body that came in contact with the shampoo.
Treatment should be limited to 4 consecutive weeks. As with other corticosteroids, therapy should be discontinued when control is achieved.
6 ADVERSE REACTIONS
In clinical trials with Clobex Shampoo, the following adverse reactions have been reported: burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia.
The table below summarizes selected adverse events that occurred in at least 1% of subjects in the Phase 2 and 3 studies for scalp psoriasis.
| Body System | Clobetasol | Vehicle |
| Propionate Shampoo | Shampoo | |
| N=558 | N=127 | |
| Skin and Appendages | 49 (8.8%) | 28 (22.0%) |
| Discomfort Skin | 26 (4.7%) | 16 (12.6%) |
| Pruritus | 3 (0.5%) | 9 (7.1%) |
| Body As A Whole | 33 (5.9%) | 12 (9.4%) |
| Headache | 10 (1.8%) | 1 (0.8%) |
The following additional local adverse reactions have been reported infrequently with other topical corticosteroids, and they may occur more frequently with the use of occlusive dressings, especially with higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: hypopigmentation, perioral dermatitis, allergic contact dermatitis, 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.
6.1 Laboratory Tests
The cortrosyn stimulation test may be helpful in evaluating patients for HPA axis suppression.
6.2 Teratogenic Effects
Pregnancy Category C: 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.
A teratogenicity study of clobetasol propionate in rats using the dermal route resulted in dose related maternal 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 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.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects: Pregnancy C: There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobex Shampoo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.3 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 quanitities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clobex Shampoo is administered to a nursing woman.
8.4 Pediatric Use
The effect of Clobex Shampoo 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 for 15 minutes to a dry scalp before lathering and rinsing. Only one of the five subjects who had suppression was tested for recovery of HPA axis, and this subject recovered after 2 weeks.
No studies have been performed in patients under the age of 12. 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 cortico-steroids in infants and children. Therefore, use is not recommended in patients under the age of 18. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios.
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.
8.5 Geriatric Use
Clinical studies of Clobetasol Propionate Shampoo did not include sufficient numbers of patients aged 65 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.
11 DESCRIPTION
Clobex Shampoo contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. The chemical name of clobetasol propionate is 21-chloro-9-fluoro-11β, 17-dihydroxy-16β-methylpregna- 1, 4-diene-3, 20-dione 17-propionate.
Clobetasol propionate has a molecular weight of 466.97 (CAS Registry Number 25122-46-7). The molecular formula is C25H32CIFO5. Clobetasol propionate is a white to practically white crystalline, odorless powder insoluble in water.
Each mL of Clobex Shampoo contains clobetasol propionate, 0.05%, in a shampoo base consisting of alcohol, citric acid, coco-betaine, polyquaternium-10, purified water, sodium citrate, and sodium laureth sulfate.
12 CLINICAL PHARMACOLOGY
Like other topical corticosteroids, Clobex Shampoo 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.
12.1 Mechanism of Action
The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear.
12.3 Pharmacokinetics
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, while inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Due to the fact that circulating levels of corticosteroids are usually below the limit of detection following application, there are no human data regarding the pharmacokinetics of topical cortico-steroids. In such cases pharmacodynamic end points, including both hypothalamic-pituitary-adrenal (HPA) axis testing and topical vasoconstriction, are used as surrogates in the assessments of systemic exposure and relative potency, respectively.
Clobex Shampoo is in the super-high range of potency in vasoconstrictor studies.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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 conducted.
14 CLINICAL STUDIES
The safety and efficacy of Clobex Shampoo has been evaluated in two clinical trials involving 290 patients with moderate to severe scalp psoriasis. In both trials, patients were treated with either Clobex Shampoo or the corresponding vehicle applied once daily for 15 minutes before lathering and rinsing for a period of 4 weeks. Efficacy results are presented in the table below.
| CLOBEX® Shampoo | CLOBEX® Shampoo Vehicle | |||
| n(%) | n(%) | |||
| Study A | Study B | Study A | Study B | |
| 1 Success rate defined as the proportion of patients with a-0 (clear) or 1 (minimal) on a 0 to 5 point physician’s Global Severity Scale for scalp psoriasis. | ||||
| 2 At four (4) weeks or last observation recorded for a subject during the treatment period (baseline if no post-baseline data were available). | ||||
| 3 Patients with 0 (clear) on a 0 to 3 point scalp psoriasis parameter scale. | ||||
| Total Number of Patients | 95 | 99 | 47 | 49 |
| Success Rate1-at Endpoint2 | 40 (42.1%) | 28 (28.3%) | 1 (2.1%) | 5 (10.2%) |
| Subjects with Scalp Psoriasis | ||||
| 17 (17.9%) | 12 (12.1%) | 3 (6.4%) | 1 (2.0%) | |
| Parameter Clear (None) at Endpoint | 21 (22.1%) | 15 (15.2%) | 0 (0%) | 2 (4.1%) |
| 35 (36.8%) | 34 (34.3%) | 5 (10.6%) | 5 (10.2%) | |
| Erythema3
Scaling3 Plaque Thickening3 | ||||
Clinical studies of Clobetasol Propionate Shampoo did not include sufficient numbers of non-Caucasian patients to determine whether they respond differently than Caucasian patients with regards to efficacy and safety.
16 HOW SUPPLIED
Clobex Shampoo is supplied in 4 fl.oz. (118 mL) bottles. NDC 0299-3847-04
STORAGE AND HANDLING
Keep it tightly closed. Store it at controlled room temperature 68˚F to 77˚F (20˚C-25˚C).
17 INFORMATION FOR PATIENTS
Patients using topical corticosteroids should received the following information and instructions:
Use of Clobex Shampoo in patients younger than 18 years of age is not recommended due to numerically high rates of HPA axis suppression.
This medication is to be used as directed by the physician and should not be used longer than the prescribed time period. It is for external use only. Avoid contact with the eyes.
This medication should not be used for any disorder other than that for which it was prescribed.
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.
Patients should report any signs of local or systemic adverse reactions to their physician.
As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician.
Patients should wash their hands after applying the medication and they should inform their physician(s) that they are using Clobex Shampoo if surgery is contemplated.
Patients should not use more than 50 g (50 mL or 1.75 fl. oz.) per week of Clobex Shampoo.
PACKAGE LABEL
Rx Only
NDC 0299-3847-04
Clobex®
(clobetasol propionate)
SHAMPOO
0.05%
4 FL OZ
(118 mL)
GALDERMA
For External Use Only.
Not for Ophthalmic Use.
Usual dosage: Apply a thin film to affected areas of the scalp once daily; apply on dry scalp and leave in place for 15 minutes before lathering and rinsing. Do not apply CLOBEX® (clobetasol propionate) Shampoo, 0.05% to the face, underarms or groin, and avoid contact with eyes and lips. Do not use for longer than 4 weeks. See package insert for complete prescribing information.
Each mL contains: Active ingredient: clobetasol propionate, 0.05%.
Excipients: alcohol, citric acid, coco-betaine, polyquaternium-10, purified water, sodium citrate, and sodium laureth sulfate.
Storage: Keep tightly closed. Store at controlled room temperature 68°F to 77°F (20°C-25°C).
US Patent Pending
Marketed by:
GALDERMA LABORATORIES, L.P.
Fort Worth, Texas 76177 USA
Manufactured by:
DPT Laboratories, Ltd.
San Antonio, Texax 78215 USA
GALDERMA is a registered trademark.
310147-0509
| CLOBEX
clobetasol propionate shampoo |
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA021644 | 03/01/2004 | |
| Labeler - Galderma Laboratories, L.P. (047350186) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| DPT Laboratories, Ltd. | 832224526 | MANUFACTURE | |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Galderma Production Canada Inc | 251676961 | MANUFACTURE | |