CLOSEL CREAM

CLOBETASOL PROPIONATE- Clobetasol propionate cream

Clobetasol Propionate Cream, USP, 0.05%

Rx only

FOR TOPICAL DERMATOLOGIC USE ONLLY – NOT FOR OPHTHALMIC, ORAL, OR

INTRAVAGINAL USE.

DESCRIPTION
Clobetasol Propionate Cream USP, 0.05% contain the active compound Clobetasol
propionate, a synthetic corticosteroid, for topical dermatologic use.
Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a
slight degree of mineralocorticoid activity.
Chemically, Clobetasol propionate is (11ß,16ß)-21-chloro-9-fluoro-11-hydroxy-16-
methyl-17-(1-oxopropoxy)-pregna-1,4-diene-3,20-dione, and it has the following
structural formula:

Clobetasol propionate has the molecular formula C25H32CIFO5 and a molecular weight of
467. It is a white to cream-colored crystalline powder insoluble in water.
Clobetasol propionate cream contains Clobetasol propionate 0.5 mg/g in a cream base
composed of cetyl alcohol, citric acid, glycol stearate, lanolin oil, methylparaben, PEG-8
stearate, polysorbate 60, propylene glycol, propylparaben, purified water, sodium citrate,
stearyl alcohol, and white petrolatum. Sodium hydroxide may be used to adjust pH.
CLINICAL PHARMACOLOGY
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 lipocortin’s.

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.

Pharmacokinetics
The extent of percutaneous absorption of topical corticosteroids is determined by many
factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressing
with hydrocortisone for up to 24 hours has not been demonstrated to increase
penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances
penetration. Topical corticosteroids can be absorbed from normal intact skin.
Inflammation and/or other disease processes in the skin may increase percutaneous
absorption.
Studies performed with Clobetasol propionate cream. indicate that they are in the super-
high range of potency as compared with other topical corticosteroids.

INDICATIONS AND USAGE

Clobetasol propionate cream are super-high potency corticosteroid formulations indicated
for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive
dermatoses. Treatment beyond 2 consecutive weeks is not recommended, and the total
dosage should not exceed 50 g/week because of the potential for the drug to suppress
the hypothalamic-pituitary-adrenal (HPA) axis. Use in pediatric patients under 12 years of
age is not recommended.
As with other highly active corticosteroids, therapy should be discontinued when control
has been achieved. If no improvement is seen within 2 weeks, reassessment of the
diagnosis may be necessary.

CONTRAINDICATIONS
Clobetasol Propionate Cream USP, 0.05% are contraindicated in those patients with a
history of hypersensitivity to any of the components of the preparations.

PRECAUTIONS

General
Clobetasol propionate cream should not be used in the treatment of rosacea or perioral
dermatitis, and should not be used on the face, groin, or axillae.
Systemic absorption of topical corticosteroids can produce reversible HPA axis
suppression with the potential for glucocorticosteroid insufficiency after withdrawal from
treatment. Manifestations of Cushing syndrome, hyperglycemia, and glucosuria can also be
produced in some patients by systemic absorption of topical corticosteroids while on
therapy.
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.
Patients receiving super-potent corticosteroids should not be treated for more than 2
weeks at a time, and only small areas should be treated at any one time due to the
increased risk of HPA suppression.
Clobetasol propionate cream produced HPA axis suppression when used at doses as
low as 2 g/day for 1 week in patients with eczema.
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 corticosteroid.
Recovery of HPA axis function is generally prompt upon discontinuation of topical
corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may
occur that require supplemental systemic corticosteroids. For information on systemic
supplementation, see prescribing information for those products.
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 cream .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.
If concomitant skin infections are present or develop, an appropriate antifungal or
antibacterial agent should be used. If a favorable response does not occur promptly,
use of Clobetasol propionate cream .should be discontinued until the infection has been
adequately controlled.

Information for Patients

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

1. This medication is to be used as directed by the physician. It is for external use

only. Avoid contact with the eyes.
2. This medication should not be used for any disorder other than that for which it
was prescribed.
3. The treated skin area should not be bandaged, otherwise covered, or wrapped
so as to be occlusive unless directed by the physician.
4. Patients should report any signs of local adverse reactions to the physician.

Laboratory Tests
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
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic
potential of Clobetasol propionate.
Studies in the rat following subcutaneous administration at dosage levels up to 50
mcg/kg/day revealed that the females exhibited an increase in the number of resorbed
embryos and a decrease in the number of living fetuses at the highest dose.
Clobetasol propionate was nonmutagenic in 3 different test systems: the Ames test, the
Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation
test.

Pregnancy
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.
Clobetasol propionate has not been tested for teratogenicity when applied topically;
however, it is absorbed percutaneously, and when administered subcutaneously it was a
significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater
teratogenic potential than steroids that are less potent.
Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the
highest dose tested (1 mg/ kg) and teratogenicity at a l dose levels tested down to
0.03 mg/ kg. These doses are approximately 1.4 and 0.04 times, respectively, the
human topical dose of Clobetasol propionate cream and ointment. Abnormalities seen
included cleft palate and skeletal abnormalities.
In rabbits, Clobetasol propionate was teratogenic at doses of 3 and 10 mcg/ kg. These
doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of
Clobetasol propionate cream and ointment. Abnormalities seen included cleft palate,
cranioschisis, and other skeletal abnormalities.
There are no adequate and we l-controlled studies of the teratogenic potential of Clobetasol
propionate in pregnant women. Clobetasol propionate cream should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 quantities in human milk. Because
many drugs are excreted in human milk, caution should be exercised when Clobetasol
propionate cream or ointment is administered to a nursing woman.

Pediatric Use
Safety and effectiveness of Clobetasol propionate cream .in pediatric patients have not
been established. Use in pediatric patients under 12 years of age is not recommended.
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.
syndrome when they are treated with topical corticosteroids. They are therefore also at
greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects
including striae have been reported with inappropriate use of topical corticosteroids in
infants and children.
HPA axis suppression, Cushing 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 fontane les, headaches, and bilateral.
papilledema.

Geriatric Use
A limited number of patients at or above 65 years of age have been treated with
Clobetasol propionate cream (n = 231) and with Clobetasol propionate ointment
(n=101) in US and non-US clinical trials. While the number of patients is too small to
permit separate analysis of efficacy and safety, the adverse reactions reported in this
population were similar to those reported by younger patients. Based on available data, no
adjustment of dosage of Clobetasol propionate cream .in geriatric patients is warranted.

ADVERSE REACTIONS
In controlled clinical trials, the most frequent adverse reactions reported for Clobetasol
propionate cream were burning and stinging sensation in 1% of treated patients. Less
frequent adverse reactions were itching, skin atrophy, and cracking and fissuring of the
skin.
In controlled clinical trials, the most frequent adverse events reported for Clobetasol
propionate ointment were burning sensation, irritation, and itching in 0.5% of treated
patients. Less frequent adverse reactions were stinging, cracking, erythema, folliculitis,
numbness of fingers, skin atrophy, and telangiectasia.
Cushing syndrome has been reported in infants and adults as a result of prolonged use
of topical Clobetasol propionate formulations.
The following additional local adverse reactions have been reported with topical
corticosteroids, and they may occur more frequently with the use of occlusive dressings
and higher potency corticosteroids. These reactions are listed in an approximately
decreasing order of occurrence: dryness, acneiform eruptions, hypopigmentation, perioral
dermatitis, allergic contact dermatitis, secondary infection, irritation, striae, and miliaria.

OVERDOSAGE
Topica lly applied Clobetasol propionate cream can be absorbed in sufficient amounts to
produce systemic effects (see PRECAUTIONS).
DOSAGE AND ADMINISTRATION
Apply a thin layer of Clobetasol propionate cream or ointment to the affected skin areas
twice daily and rub in gently and completely (see INDICATIONS AND USAGE).
Clobetasol propionate cream .are super-high potency topical corticosteroids; therefore,
treatment should be limited to 2 consecutive weeks and amounts greater than
50 g/week should not be used.
As with other highly active corticosteroids, therapy should be discontinued when control
has been achieved. If no improvement is seen within 2 weeks, reassessment of
diagnosis may be necessary.
Clobetasol propionate cream .should not be used with occlusive dressings.
Geriatric Use: In studies where geriatric patients (65 years of age or older, see
PRECAUTIONS) have been treated with Clobetasol propionate cream or ointment, safety
did not differ from that in younger patients; therefore, no dosage adjustment is
recommended.

HOW SUPPLIED
Clobetasol Propionate Cream, USP, 0.05% is supplied in 20-g tubes.
Store cream between 30° C (59° and 86° F).
Clobetasol propionate cream should not be refrigerated.
Marketing Authorization Holder:
Giuliano’s pharmacy
Unit A, Plot 11-13 Dukes Road, Butabika
Kampala, Uganda

Manufacturer:
By Bellazuri Limited with German Technology
Unit A, Plot 11-13 Dukes Road, Butabika
Kampala, Uganda
Rx only