Alya Putri Khairani C

1
Clobetasol Propionate and Urea Cream
Clobetasol Propionate
Description
Clobetasol Propionate contains 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. Clobetasol is commonly used in the form of cream and ointment

Each gram of the 0.05% cream contains Clobetasol Propionate 0.5 mg in a cream base of Propylene glycol,
Glyceryl monostearate, Cetostearyl alcohol, Glyceryl stearate, PEG 100 stearate, White wax, Chlorocresol,
Sodium citrate anhydrous, Citric acid anhydrous, and Purified water.

Each gram of the 0.05% ointment contains Clobetasol Propionate 0.5 mg in a base of Propylene glycol,
Sorbitan sesquioleate, and White petrolatum

Mechanism of Action
Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive
properties.
(1) Anti-inflammatory
Corticosteroids are thought to exert their potent anti-inflammatory effects by inhibiting the release of
Phospholipase A2, an enzyme responsible for the formation of Prostaglandins, Leukotrienes, and other
derivatives of the Arachidonic Acid pathway. Genes known to be upregulated by corticosteroids and that play a
role in the resolution of inflammation include Lipocortin and p11/Calpactin-binding proteins. Lipocortin I
inhibits phospholipase A2, reducing the release of Arachidonic Acid from phospholipids. Corticosteroids also
decrease the release of Interleukin 1 (IL-1), a pro-inflammatory cytokine, from Keratinocytes. Other proposed
mechanisms for the anti-inflammatory effects of corticosteroids include inhibition of phagocytosis and
stabilization of lysosomal membranes of phagocytizing cells
(2) Immunosuppresive effects
Corticosteroids suppress the production and effects of humoral factors involved in the inflammatory
response, inhibit leukocyte migration to sites of inflammation, and interfere with the function of endothelial
cells, granulocytes, mast cells, and fibroblasts. In addition, several cytokines are directly affected by
corticosteroids, including IL-1, Tumor Necrosis Factor- (TNF- ), Granulocyte-macrophage Colony-stimulating
Factor, and IL-8. These effects may also be a result of the steroid action on Antigen Presenting Cells (APC)
(3) Anti-prolifetarive effects
The antiproliferative effect of topical corticosteroids is mediated by inhibition of DNA synthesis and
mitosis, partly explaining the therapeutic action of these drugs in scaling dermatoses. Fibroblast
activity and collagen formation are also inhibited by topical corticosteroids
(4) Vasoconstriction
The mechanism by which corticosteroids induce vasoconstriction is not yet completely clear. It is thought to be
related to inhibition of natural vasodilators such as histamine, bradykinins, and prostaglandins. Topical steroids
cause capillaries in the superficial dermis to constrict, thus reducing erythema. The ability of a given
corticosteroid agent to cause vasoconstriction usually correlates with its anti-inflammatory potency

Pharmacokinetic

Alya Putri Khairani C

1
Topical corticosteroid research has focused on strategies to optimize potency while minimizing side effects. One
strategy is to develop compounds with enhanced anti-inflammatory effects and minimal unwanted atrophogenic
and adrenal suppressive effects. In this sense, progress has been made with the development of glucocorticoid
molecules that, while retaining high activity in the skin following topical application, are quickly broken down into
inactive metabolites, thereby mitigating systemic and possibly some local toxic effects

Indications and Usage

Certain variables must be considered when treating skin disorders with topical glucocorticoids. For example, the
responsiveness of diseases to topical glucocorticoids varies:

Responsiveness of Dermatoses to Topical Application of Corticosteroid

Highly Responsive
Psoriasis (intertriginous)
Atopic Dermatitis (children)
Seborrheic Dermatitis
Intertrigio

Moderately Responsive
Psoriasis
Atopic Dermatitis (adult)
Nummular Eczema
Primary Irritant Dermatitis
Papular Urticaria

Less Responsive
Palmo-plantar Psoariasis
Psoriasis of Nails
Dyshidrotic Eczema
Lupus Erythromatosus
Pemphigus

Parapsoriasis
Lichen planus
Lichen Simplex Chronicus
Granuloma annulare
Necrobiosis Lipoidica Diabeticorum
Sarcoidosis
Allergic Contact Dermatitis, acute
phase
Insect bites
Clobetasol Propionate ointment is a super-high potency corticosteroid formulation indicated for the relief of the
inflammatory and pruritic manifestation of corticosteroid responsive dermatoses. Treatment beyond 2 consecutive
weeks is not recommended, and the total dosage should not exceed 50 gr per week because of the potential for
the drug to suppress the Hypothalamic-Pituitary Adrenal (HPA) axis. Use in children under 23 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

Dosage Regimen
Lagos and Maibach observed in a recent review of the literature that for superpotent corticosteroids like Clobetasol,
once-daily application was as beneficial as twice-daily application. Likewise, there was no difference or only a slight
difference with once or twice daily application of potent or moderately potent corticosteroids. The authors
concluded that once-daily application of topical corticosteroids may be preferable, may decrease the risks of
side effects and tachyphylaxis, decrease the cost of therapy, and improve the patient's compliance. As a working
rule, not more than 45 g/week of potent or 100 g/week of weak or moderately potent topical corticosteroid should
be applied (without occlusion) if systemic absorption is to be avoided

Clinical Formulation
(1) Initiating Therapy
Before choosing a topical glucocorticoid preparation, one must consider the area of the body that is to be
treated because regional differences greatly affect the activity of the topical agent
Highly responsive diseases will usually respond to weak steroid preparations, whereas less-responsive
diseases require medium or high-potency topical steroids
Low-potent preparations should be used on the face and intertriginous areas
Very potent corticosteroids frequently under occlusion are usually required on Hyperkeratotic or Lichenified
Dermatoses and for disease of the palms and soles
(2) Monitoring Therapy
Application of corticosteroids to large surface areas, occlusion, higher concentrations, or more potent
derivatives directly increase the risk of Hypothalamicpituitary-axis suppression. If the latter is suspected,
laboratory analyses that include a complete blood cell count, a chemistry panel, and a baseline morning

Alya Putri Khairani C

1
cortisol level should be performed. In a patient with confirmed HPAxis suppression, the simultaneous institution
of oral steroid supplementation and a reduction of potency and amount of topical steroid are needed

Risks and Precautions

Cutaneous adverse effects can result from the small percentage of percutaneously absorbed corticosteroid or may
also result from its transient presence onto the skin. Continued use of topical corticosteroids may also lead to
tachyphylaxis. Consideration for prescribing topical corticosteroids to prevent side effects:
Highly potent formulations should be used for short periods (2 to 3 weeks) or intermittently
Reduce frequency of application (e.g., application only in the morning, alternate-day therapy, weekend
use) once disease control is partially achieved
Topical corticosteroids should be avoided on ulcerated or atrophic skin, and on skin with co-existent
infectious dermatoses
Sudden discontinuation should be avoided after prolonged use to prevent rebound phenomena
Special guidelines should be followed when treating certain body areas (e.g., intertriginous areas) or
certain populations (e.g., children or the elderly) to prevent the occurrence of local or systemic adverse
effects
Laboratory tests should be considered if systemic absorption of corticosteroids is suspected
Use combination therapy when clinically indicated (e.g., addition of topical tretinoin or keratolytics)
Complications
Atrophic changes
Dermal atrophy develops from the direct antiproliferative effects of topical corticosteroids on fibroblasts,
with inhibition of collagen and mucopolysaccharide synthesis, resulting in loss of dermal support
Acneiform reactions
The development or exacerbation of dermatoses of the face, including steroid rosacea, acne, and perioral
dermatitis, is a well-known effect of topical corticosteroids. Although steroids initially lead to the
suppression of inflammatory papules and pustules, patients become addicted because they notice that the
lesions flare when treatment is withdrawn. This frequently leads to the continued use of greater potency
topical corticosteroids
Hyperthricosis
Hypertrichosis occurs rarely in women and children who apply potent corticosteroids to the face
Pigmentary changes
Decreased pigmentation is a common side effect of topical steroid use. The pigment generally returns after
discontinuation of therapy
Development of infections
Topical corticosteroids are responsible for exacerbating and/or masking cutaneous infectious diseases. The
incidence of skin infection during corticosteroid therapy varies but is probably between 16 percent and 43
percent. Tinea versicolor, disseminated Alternaria infection, and Dermatophytosis, including Tinea
Incognito (masked dermatophyte infection), can develop. Topical corticosteroids have also an effect on
prolongation or mitigation of herpes simplex, molluscum contagiosum, and scabies infection
Allergic reactions
Persistence or worsening of skin diseases occurs as a result of contact hypersensitivity to topical
corticosteroids. The prevalence to topical corticosteroid sensitization ranges between 0.2 percent and 6.0
percent, and increases with prolonged exposure and the selection of certain drugs
Systemic adverse effects
Ocular effects : can cause Glaucoma (apply at the eye)
Suppression of the Hypothalamic-Pituitary-Adrenal Axis : can cause Iatrogenic Cushing Syndrome
Metabolic side effects : increase glucose production

Urea Cream
Definition
Urea in a compatible cream vehicle or ointment base is a keratolytic emollient (moisturizer), which is a gentle, yet
potent, tissue softener for nails and/or skin. As humectants, urea is used in concentration of 2-20% in creams and
lotions. As keratolytic agents, it is used in 20% concentration in diseases such as Ichtyosis vulgaris, Hyperkeratosis
of palms and soles, Xerosis, and Keratosis pilaris. Concentration of 30-50% applied to the nail plate have been
useful in softening the nail prior to avulsion

Mechanism of Action

Urea has a softening and moisturizing effect on the Stratum Corneum. Urea allegedly increase the water content of
Stratum Corneum, presumably as a result of the hygroscopic characteristics of this naturally occurring molecule.
Urea is a also a keratolytic. The mechanism of action appears to involve alterations in prekeratin and keratin,
leading to increased solubilization. In addition, urea may break hydrogen bonds that keep the Stratum Corneum
intact
Pharmacokinetic

Alya Putri Khairani C

1
Urea is absorbed percutaneously, although the precise amount absorbed is not well documented. It is distributed
predominantly in the extracellular space and excreted in the urine. Urea is a natural product of metabolism, and
systemic toxicities with topical application do not occur

Indication and Uses

Urea cream is indicated for use in the topical treatment for debridement and promotion of normal healing of
hyperkeratotic surface lesions, particularly where healing is retarded by local infection, necrotic tissue, fibrinous or
purulent debris or eschar

Precautions

For external use only. Avoid contact with eyes, lips, or mucous membranes

Adverse Effects

Transient stinging, burning itching or irritation may occur and normally disappear on discontinuing medication

Dosage and Administration

Apply Urea cream to affected skin area(s) or damaged mao; tissue twice a day or as directed by a physician

References:
Fitzpatricks Dermatology in General Medicine 7th edition Part 11 Section
36
www.dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?
archiveid=5866
Katzung Basic and Clinical Pharmacology 10th edition chapter X