CLOBEX - clobetasol propionate shampoo
Galderma Laboratories, L.P.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use CLOBEX® Shampoo safely and effectively. See full prescribing information for CLOBEX® Shampoo. CLOBEX® (clobetasol propionate) Shampoo, 0.05% for topical use only Initial U.S. Approval: 1985
INDICATIONS AND USAGE
CLOBEX (clobetasol propionate) Shampoo, 0.05% is a corticosteroid indicated for the treatment of moderate to severe scalp psoriasis in subjects 18 years of age and older. (1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Shampoo, 0.05% (3)
WARNINGS AND PRECAUTIONS
Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis at the lowest doses tested. (5.1)
The most common adverse reactions are burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia. (6.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
CLOBEX Shampoo, 0.05%, is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe forms of scalp psoriasis in subjects 18 years of age and older. Treatment should be limited to 4 consecutive weeks. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week.
Patients should be instructed to use CLOBEX Shampoo, 0.05%, for the minimum time period necessary to achieve the desired results [see Dosage and Administration (2)].
Use in patients younger than 18 years of age is not recommended due to numerically high rates of hypothalamic-pituitary-adrenal (HPA) axis suppression [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].
CLOBEX Shampoo, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use.
CLOBEX Shampoo, 0.05%, 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.
The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week.
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, 0.05%.
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.
Treatment should be limited to 4 consecutive weeks. As with other corticosteroids, therapy should be discontinued when control is achieved. If complete disease control is not achieved after 4 weeks of treatment with CLOBEX Shampoo, 0.05%, treatment with a less potent topical steroid may be substituted. If no improvement is seen within 4 weeks, reassessment of the diagnosis may be necessary.
CLOBEX Shampoo, 0.05%, should not be used with occlusive dressings (shower cap or bathing cap) unless directed by a physician.
Shampoo, 0.05%, w/w. Each gram of CLOBEX Shampoo, 0.05%, contains 0.5 mg of clobetasol propionate in a translucent, colorless to pale yellow viscous liquid.
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.
The effect of CLOBEX (clobetasol propionate) Shampoo, 0.05% on HPA axis suppression was evaluated in one trial in adolescents 12 to 17 years of age. In this trial, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with CLOBEX (clobetasol propionate) Shampoo, 0.05% applied once daily for 15 minutes to a dry scalp before lathering and rinsing.
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 adrenocorticotropic hormone (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.
Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.
Use of more than one corticosteroid-containing product at the same time may increase the total systemic exposure.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios [see Use in Specific Populations (8.4)].
If irritation develops, CLOBEX 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. Clinical diagnosis of allergic contact dermatitis can be confirmed with patch testing.
In the presence of dermatologic 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, 0.05%, should be discontinued until the infection has been adequately controlled.
Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids.
Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis.
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 clinical trials with CLOBEX Shampoo, 0.05%, the following adverse reactions have been reported: headache, burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia.
Table 1 summarizes selected adverse reactions that occurred in at least 1% of subjects in the Phase 2 and 3 studies for scalp psoriasis.
CLOBEX Shampoo, 0.05%
Vehicle Shampoo, 0.05%
|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%)|
Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.
Because 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 Shampoo, 0.05%.
Teratogenic effects: Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Therefore, CLOBEX Shampoo, 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 no-observed-effect-level (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 human milk. Because many drugs are excreted in human milk, caution should be exercised when CLOBEX Shampoo, 0.05%, is administered to a nursing woman.
Use of CLOBEX Shampoo, 0.05%, in patients under 18 years old is not recommended due to potential for HPA axis suppression [see Warnings and Precautions (5.1)].
The effect of CLOBEX (clobetasol propionate) Shampoo, 0.05%, on HPA axis suppression was evaluated in one trial in adolescents 12 to 17 years of age with moderate to severe scalp psoriasis with involvement of at least 25% of the scalp. In this trial, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with CLOBEX (clobetasol propionate) Shampoo, 0.05%, applied once daily for 15 minutes to a dry scalp before lathering and rinsing. Only 1 of the 5 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 corticosteroids in infants and children. Therefore, use is not recommended in patients under the age of 18.
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.
Clinical studies of CLOBEX Shampoo, 0.05%, did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. 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.
Topically applied, CLOBEX Shampoo, 0.05%, can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1)].
CLOBEX (clobetasol propionate) Shampoo, 0.05%, contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical 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.
It has the following structural formula:
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 gram of CLOBEX (clobetasol propionate) Shampoo, 0.05%, contains 0.5 mg of clobetasol propionate in a translucent, colorless to pale yellow viscous liquid shampoo base consisting of alcohol, citric acid, coco-betaine, polyquaternium-10, purified water, sodium citrate, and sodium laureth sulfate.
Like other topical corticosteroids, CLOBEX (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.
CLOBEX Shampoo, 0.05%, is in the super-high range of potency as demonstrated in vasoconstrictor studies in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.
Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression
In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, use of CLOBEX (clobetasol propionate) Shampoo, 0.05%, resulted in demonstrable HPA axis suppression in 5 out of 12 (42%) adolescent subjects [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].
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.
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.
The safety and efficacy of CLOBEX Shampoo, 0.05%, have been evaluated in two clinical trials involving 290 subjects with moderate to severe scalp psoriasis. In both trials, subjects 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 Table 2 below.
|CLOBEX Shampoo, 0.05% N (%)||Shampoo Vehicle n (%)|
|Study A||Study B||Study A||Study B|
|Total Number of Subjects||95||99||47||49|
|Success Rate1 at Endpoint2||40 (42.1%)||28 (28.3%)||1 (2.1%)||5 (10.2%)|
Subjects with Scalp Psoriasis Parameter
Clear (None) at Endpoint
|17 (17.9%)||12 (12.1%)||3 (6.4%)||1 (2.0%)|
|21 (22.1%)||15 (15.2%)||0 (0%)||2 (4.1%)|
|Plaque Thickening3||35 (36.8%)||34 (34.3%)||5(10.6%)||5 (10.2%)|
1Success rate defined as the proportion of subjects with a-0 (clear) or 1 (minimal) on a 0 to 5 point physician's Global Severity Scale for scalp psoriasis.
2At four (4) weeks or last observation recorded for a subject during the treatment period (baseline if no post-baseline data were available).
3Subjects with 0 (clear) on a 0 to 3 point scalp psoriasis parameter scale.
Clinical studies of CLOBEX Shampoo, 0.05%, did not include sufficient numbers of non-Caucasian subjects to determine whether they respond differently than Caucasian subjects with regards to efficacy and safety.
CLOBEX Shampoo, 0.05%, is a translucent, colorless to pale yellow viscous liquid, supplied in 4 fl. oz. (118 mL) bottles.
Storage: Keep tightly closed. Store at USP controlled room temperature 68˚ to 77˚F (20˚ - 25˚C), with excursions permitted between 59˚ and 86˚F (15˚ - 30˚C).
See FDA-approved patient labeling (Patient Information)
Information for Patients
Inform the patient using topical corticosteroids to adhere to following instructions:
Important: For use on the scalp only. Do not get CLOBEX Shampoo near or in your eyes, mouth or vagina.
Read the Patient Information that comes with CLOBEX Shampoo before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.
What is CLOBEX Shampoo?
You should not use CLOBEX Shampoo:
CLOBEX Shampoo should not be used in children under 18 years of age.
What should I tell my doctor before using CLOBEX Shampoo?
Before you use CLOBEX Shampoo, tell your doctor if you:
Talk to your doctor about the best way to feed your baby if you use CLOBEX Shampoo.
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids. You should not use other products that contain corticosteroids while you are using CLOBEX Shampoo. Ask your doctor or pharmacist if you are not sure.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist if you get a new medicine.
How should I use CLOBEX Shampoo?
See the “Instructions for Use” at the end of the Patient Information for detailed information about the right way to use CLOBEX Shampoo.
What are the possible side effects of CLOBEX Shampoo?
CLOBEX Shampoo can pass through your skin. Too much CLOBEX Shampoo passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check how well your adrenal glands are working.
The most common side effects of CLOBEX Shampoo include:
If you go to another doctor for illness, injury or surgery, tell that doctor that you are using CLOBEX Shampoo.
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of CLOBEX Shampoo. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Galderma Laboratories, L.P. at 1-866-735-4137.
How should I store CLOBEX Shampoo?
Keep CLOBEX Shampoo and all medicines out of the reach of children.
General information about CLOBEX Shampoo
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use CLOBEX Shampoo for a condition for which it was not prescribed. Do not give CLOBEX Shampoo to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information leaflet summarizes the most important information about CLOBEX Shampoo. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about CLOBEX Shampoo that is written for health professionals.
What are the ingredients in CLOBEX Shampoo?
Active ingredient: clobetasol propionate
Inactive ingredients (shampoo base): alcohol, citric acid, coco-betaine, polyquaternium-10, purified water, sodium citrate and sodium laureth sulfate.
Instructions for Use
Important: For use on the scalp only. Do not get CLOBEX Shampoo near or in your eyes, mouth or vagina.
Read the Instructions for Use that comes with CLOBEX Shampoo before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.
How to apply CLOBEX Shampoo to your scalp:
Your hair should be dry when you apply CLOBEX Shampoo to your scalp.
Do not get CLOBEX Shampoo on your face, in your eyes or on your lips. If CLOBEX Shampoo does get on these areas, rinse well with water.
Step 1: To apply CLOBEX Shampoo to your scalp, part your hair at the area where it is to be applied.
Step 2: Hold the bottle of CLOBEX Shampoo over the affected area. Gently squeeze the bottle and apply a small amount of shampoo to the affected area.
Step 3: Gently rub CLOBEX Shampoo into the affected area so that only the affected area is covered with a thin, even layer of CLOBEX Shampoo.
Step 4: Repeat Steps 1 through 3 to apply CLOBEX Shampoo to other affected areas on your scalp as instructed by your doctor.
Step 5: Wash your hands after applying CLOBEX Shampoo.
Step 6: Leave CLOBEX Shampoo on your scalp for 15 minutes. You should not bandage or cover your head with a shower cap, bathing cap, or a towel while CLOBEX Shampoo is on your scalp, unless your doctor tells you to.
Step 7: After 15 minutes have passed, wet your hair with water. Lather and rinse your hair and scalp completely. Rinse any other parts of your body that come into contact with CLOBEX Shampoo, such as your hands, face, neck and shoulders.
No other shampoo is needed, but you may wash your hair with a non-medicated shampoo after using CLOBEX Shampoo.
This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.
GALDERMA LABORATORIES, L.P.
Fort Worth, Texas 76177 USA
DPT Laboratories, Ltd.
San Antonio, Texas 78215 USA
G Production Inc.
Baie d’Urfé, QC, H9X 3S4 Canada
Made in Canada
GALDERMA is a registered trademark.
US Patent Nos. 7,316,810 and 7,700,081
Clobex® (clobetasol propionate)
4 FL OZ
For External Use Only.
Not for Ophthalmic Use.
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 68F to 77F (20C-25C).
US Patent Pending
GALDERMA LABORATORIES, L.P.
Fort Worth, Texas 76177 USA
G Production Inc.
Baie d'Urfe, QC, H9X 3S4 Canada
Made in Canada
GALDERMA is a registered trademark.
clobetasol propionate shampoo
|Labeler - Galderma Laboratories, L.P. (047350186)|
|DPT Laboratories, Ltd.||832224526||manufacture(0299-3847)|
|G Production, Inc.||251676961||manufacture(0299-3847)|