CLOBETASOL PROPIONATE
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clobetasol propionate shampoo
Sandoz, Inc.
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Clobetasol Propionate Shampoo, 0.05%, 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. 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 mL of Clobetasol Propionate Shampoo, 0.05%, 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
Like other topical corticosteroids, 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.
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
corticosteroids. 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.
In studies evaluating the potential for
hypothalamic-pituitary-adrenal (HPA) axis suppression, use of Clobetasol Propionate Shampoo, 0.05%, resulted in demonstrable HPA axis
suppression in 5 out of 12 (42%) adolescent patients (see PRECAUTIONS).
Clobetasol Propionate Shampoo is in the super-high range of potency in vasoconstrictor studies.
The safety and efficacy of Clobetasol Propionate Shampoo, 0.05% has been evaluated in two clinical trials involving 290 patients with moderate to severe scalp psoriasis. In both trials, patients were treated with either Clobetasol Propionate 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.
| Clobetasol Propionate Shampoo n (%) Study A | Clobetasol Propionate Shampoo n (%) Study B | Clobetasol Propionate Shampoo Vehicle n (%) Study A | Clobetasol Propionate Shampoo Vehicle n (%) Study B |
Total Number of Patients | 95 | 99 | 47 | 49 |
Sucess Rate1 at Endpoint2 | 40 (42.1%) | 28 (28.3%) | 1 (2.1%) | 5 (10.2%) |
Subjects with Scalp Psoriasis Parameter Clear (None) at Endpoint Erythema3 Scaling3 Plaque Thickening3 |
17 (17.9%) 21 (22.1%) 35 (36.8%) |
12 (12.1% 15 (15.2%) 34 (34.3%) |
3 (6.4%) 0 (0%) 5 (10.6%) |
1 (2.0%) 2 (4.1%) 5 (10.2%) |
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.
Clinical studies of Clobetasol Propionate Shampoo, 0.05% did, not include sufficient numbers of non-Caucasian patients to determine whether they respond differently than Caucasian patients with regards to efficacy and safety.
Clobetasol Propionate 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 (see PRECAUTIONS). Treatment should be limited to 4 consecutive weeks
because of the potential for the drug to suppress the
hypothalamic-pituitary-adrenal (HPA) axis. The total dosage should not exceed 50
g (50 mL or 1.75 fl. oz.) per week (see DOSAGE AND ADMINISRATION).
Patients should be instructed to use Clobetasol Propionate Shampoo,
0.05%, for the minimum time period necessary to achieve the desired results (see PRECAUTIONS).
Use in patients younger than 18 years of age is not recommended
due to numerically high rates of HPA axis suppression (see PRECAUTIONS, Pediatric Use).
There were insufficient numbers
of non-Caucasian patients to determine whether they responded differently than
Caucasian patients with regards to efficacy and safety.
Use of Clobetasol Propionate Shampoo, 0.05%, is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.
General: 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 Clobetasol Propionate Shampoo, 0.05% on HPA axis suppression was
evaluated in one study in adolescents 12 to 17 years of age. In th is study, 5
of 12 evaluable subjects developed suppression of their HPA axis following 4
weeks of treatment with Clobetasol Propionate Shampoo, 0.05% applied
once daily for 15 minutes to a dry scalp before lathering and
rinsing.
Pediatric patients may be more susceptible to systemic toxicity from
equivalent doses due to their larger skin surface to body mass ratios. (see PRECAUTIONS - Pediatric Use).
If irritation develops, Clobetasol Propionate 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 Clobetasol Propionate Shampoo should be discontinued until the infection has been
adequately controlled.
Although Clobetasol Propionate 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. Clobetasol Propionate 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.
The cortrosyn stimulation test may be helpful in evaluating patients for HPA axis suppression.
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 Clobetasol Propionate Shampoo, 0.05% on fertility have not been conducted.
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 Clobetasol Propionate 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 Clobetasol Propionate Shampoo.
There are no adequate and
well-controlled studies of the teratogenic potential of clobetasol propionate in
pregnant women. Clobetasol Propionate Shampoo should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
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 Clobetasol Propionate Shampoo, 0.05%, is administered to a nursing woman.
Use of Clobetasol Propionate Shampoo, 0.05%, in patients under 18 years old is not recommended
due to potential for HPA axis suppression (see PRECAUTIONS: General).
The effect of Clobetasol Propionate Shampoo, 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 Clobetasol Propionate Shampoo, 0.05%, 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 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 Clobetasol Propionate Shampoo, 0.05%, 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.
In clinical trials with Clobetasol Propionate 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 Propionate Shampoo N=558 | Vehicle Shampoo N=127 |
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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%) |
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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.
Topically applied, Clobetasol Propionate Shampoo can be absorbed in sufficient amounts to produce systemic effects. (see PRECAUTIONS).
Clobetasol Propionate 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 Clobetasol Propionate 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.
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 four weeks of treatment with Clobetasol Propionate 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. Clobetasol Propionate Shampoo should not be used with occlusive
dressings unless directed by a physician.
Clobetasol Propionate Shampoo is supplied in 4 fl.oz. (118 mL) bottles.
NDC 0781-7137-04
For External Use Only
Not for Ophthalmic (Eye) Use
Clobetasol Propionate Shampoo,
0.05%
Read the Patient Information that comes with Clobetasol Propionate Shampoo before you start using it and each time you get a refill. There may be
new information. This leaflet does not take the place of talking with your
doctor about your medical condition or your treatment.
What is the most important information I should know about Clobetasol Propionate Shampoo?
What is Clobetasol Propionate Shampoo?
Clobetasol Propionate Shampoo is a
medicine called a topical (skin use only) corticosteroid. It is used for a short
time to treat forms of scalp psoriasis. Clobetasol Propionate Shampoo is a super-high potent
(very strong) topical corticosteroid. It is very important that you use Clobetasol Propionate Shampoo only as directed in order to avoid serious side effects.
Who should not use Clobetasol Propionate Shampoo?
Do not use Clobetasol Propionate Shampoo if you are
allergic to any of its ingredients, or to any other corticosteroid. The active
ingredient is clobetasol propionate. See the end of this leaflet for a complete
list of ingredients in Clobetasol Propionate Shampoo. Ask your doctor or pharmacist if you
need a list of other corticosteroids.
Clobetasol Propionate Shampoo is not recommended for
use by patients under 18 years of age. Children have smaller body sizes and have
a higher chance of side effects.
What should I tell my
doctor before using Clobetasol Propionate Shampoo?
Tell your doctor:
Rx only
Manufactured by:
G Production Inc.
Baie d’Urfé, QC, H9X 3S4 Canada for
Sandoz Inc.
Princeton, NJ 08540
Made in Canada.
P51964-0
Revised: October 2011
CLOBETASOL PROPIONATE
clobetasol propionate shampoo |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
NDA authorized generic | NDA021644 | 12/22/2011 |
Labeler - Sandoz, Inc. (110342024) |
Establishment | |||
Name | Address | ID/FEI | Operations |
G Production, Inc. | 251676961 | manufacture |
Revised: 01/2011 Sandoz, Inc.