Clovate

Cream: White semisolid mass.
Clobetasol Propionate BP 0.5% w/w, Cream base q.s.
Ointment: White semisolid mass filled in collapsible aluminium tube with white screw cap.
Each gram contains: Clobetasol Propionate BP 500 mcg (0.05% w/w) in a suitable ointment base q.s.

Pharmacotherapeutic group: Corticosteroids, very potent (group IV). ATC code: D07AD01.
Pharmacology: Pharmacodynamics: Mechanism of action: Topical corticosteroids act as anti-inflammatory agents via multiple mechanisms to inhibit late phase allergic reactions including decreasing the density of mast cells, decreasing chemotaxis and activation of eosinophils, decreasing cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibiting the metabolism of arachidonic acid.
Pharmacodynamic effects: Topical corticosteroids have anti-inflammatory, antipruritic, and vasoconstrictive properties.
Ointment: The major effect of Clobetasol propionate on skin is a non-specific anti-inflammatory response, partially due to vasoconstriction and decrease in collagen synthesis.
Pharmacokinetics: Absorption: Topical corticosteroids can be systemically absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption. Mean peak plasma clobetasol propionate concentrations of 0.63 nanogram/mL occurred in one study eight hours after the second application (13 h after an initial application) of 30 g clobetasol propionate 0.05% ointment to normal individuals with healthy skin. Following the application of a second dose of 30 g clobetasol propionate cream 0.05%, mean peak plasma concentrations were slightly higher than the ointment and occurred 10 h after application. In a separate study, mean peak plasma concentrations of approximately 2.3 nanograms/mL and 4.6 nanograms/mL occurred respectively in patients with psoriasis and eczema three hours after a single application of 25 g clobetasol propionate 0.05% ointment.
Distribution: The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection.
Metabolism: Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver.
Elimination: Topical corticosteroids are excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

For the short-term use in the treatment of steroid responsive dermatoses resistant to other less potent topical corticosteroids such as: Cream: Psoriasis (excluding widespread plaque psoriasis). Recalcitrant dermatoses, Lichen planus, Discoid lupus erythematosus, Other skin conditions which do not respond satisfactorily to less potent steroids.
Ointment: For short-term use in the treatment of steroid responsive dermatoses resistant to other less potent topical corticosteroid such as: contact dermatitis, atopic dermatitis, eczema, lichen planus, bug bites, psoriasis and alopecia areata.

Cream: Clobetasol propionate cream to be applied thinly and gently rub to the affected area once or twice daily until improvement occurs. Therapy should be discontinued when control is achieved. Apply Clobetasol propionate cream in a sufficient quantity covering the interested zone and allow adequate time for absorption after each application or as prescribed by the physician.
Ointment: Clobetasol propionate ointment to be applied sparingly to the affected area once or twice daily until improvement occurs. Therapy should be discontinued when control is achieved. Apply Clobetasol propionate ointment in a sufficient quantity covering the interested zone and massage until complete absorption of the product.
Or as prescribed by the physician.

Symptoms: Topically applied clobetasol may be absorbed in sufficient amounts to produce systemic effects. Acute overdosage is very unlikely to occur; however, in the case of chronic overdosage or misuse, the features of hypercortisolism may occur.
Management: In the event of overdose, clobetasol should be withdrawn gradually by reducing the frequency of application or by substituting a less potent corticosteroid because of the risk of glucocorticosteroid insufficiency.
Further management should be as clinically indicated or as recommended by the national poisons center, where available.

Hypersensitivity to Clobetasol propionate or any of the excipients in this product.
Cream: The following conditions should not be treated with Clobetasol propionate: Untreated cutaneous infections; Rosacea; Acne vulgaris; Pruritus without inflammation; Perianal and genital pruritus; Perioral dermatitis.
Clobetasol is contraindicated in dermatoses in children under one year of age, including dermatitis and nappy eruptions.

Cream: Cases of osteonecrosis serious infections (including necrotizing fasciitis) and systemic immunosuppression (sometimes resulting in reversible Kaposi's sarcoma lesions) have been reported with long-term use of clobetasol propionate beyond the recommended doses. In some cases patients used concomitantly other potent oral/topical corticosteroids or immunosuppressors (e.g., methotrexate, mycophenolate mofetil). If treatment with local corticosteroids is clinically justified beyond 4 weeks, a less potent corticosteroid preparation should be considered.
Clobetasol should be used with caution in patients with a history of local hypersensitivity to other corticosteroids or to any of the excipients in the preparation. Local hypersensitivity reactions may resemble symptoms of the condition under treatment.
Manifestations of hypercortisolism (Cushing's syndrome) and reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, leading to glucocorticosteroid insufficiency, can occur in some individuals as a result of increased systemic absorption of topical steroids. If either of the previously mentioned is observed, withdraw the drug gradually by reducing the frequency of application, or by substituting a less potent corticosteroid. Abrupt withdrawal of treatment may result in glucocorticosteroid insufficiency.
Risk factors for increased systemic effects are: Potency and formulation of topical steroid.
Duration of exposure: Application to a large surface area.
Use on occluded areas of skin (e.g., on intertriginous areas or under occlusive dressings (in infants the nappy may act as an occlusive dressing).
Increasing hydration of the stratum corneum.
Use on thin skin areas such as the face: Use on broken skin or other conditions where the skin barrier may be impaired.
In comparison with adults, children and infants may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic adverse effects. This is because children have an immature skin barrier and a greater surface area to body weight ratio compared with adults.
Infection risk with occlusion: Bacterial infection is encouraged by the warm, moist conditions within skin folds or caused by occlusive dressings. When using occlusive dressings, the skin should be cleansed before a fresh dressing is applied.
Use in Psoriasis: Topical corticosteroids should be used with caution in psoriasis as rebound relapses, development of tolerances, risk of generalised pustular psoriasis and development of local or systemic toxicity due to impaired barrier function of the skin have been reported in some cases. If used in psoriasis careful patient supervision is important.
Concomitant infection: Appropriate antimicrobial therapy should be used whenever treating inflammatory lesions which have become infected. Any spread of infection requires withdrawal of topical corticosteroid therapy and administration of appropriate antimicrobial therapy.
Chronic leg ulcers: Topical corticosteroids are sometimes used to treat the dermatitis around chronic leg ulcers. However, this use may be associated with a higher occurrence of local hypersensitivity reactions and an increased risk of local infection.
Application to the face: Application to the face is undesirable as this area is more susceptible to atrophic changes.
If used on the face, treatment should be limited to 5 days.
Application to the eyelids: If applied to the eyelids, care is needed to ensure that the preparation does not enter the eye, as cataract and glaucoma might result from repeated exposure. If clobetasol does enter the eye, the affected eye should be bathed in copious amounts of water.
Visual disturbance: Visual disturbance has been reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Clobetasol cream contains paraffin. Instruct patients not to smoke or go near naked flames due to the risk of severe burns. Fabric (clothing, bedding, dressings etc.) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.
Topical steroid withdrawal syndrome: Long term use of topical steroids can result in the development of rebound flares after stopping treatment (topical steroid withdrawal syndrome). A severe form of rebound flare can develop which takes the form of a dermatitis with intense redness, stinging and burning that can spread beyond the initial treatment area. It is more likely to occur when delicate skin sites such as the face and flexures are treated. Should there be a reoccurrence of the condition within days to weeks after successful treatment a withdrawal reaction should be suspected. Re-application should be with caution and specialist advise is recommended in these cases or other treatment options should be considered.
The label will state very strong steroid.
Effects on ability to drive and use machines: There have been no studies to investigate the effect of clobetasol on driving performance or the ability to operate machinery. A detrimental effect on such activities would not be anticipated from the adverse reaction profile of topical clobetasol.
Use in Children: In infants and children under 12 years of age, long-term continuous topical corticosteroid therapy should be avoided where possible, as adrenal suppression can occur Children are more susceptible to develop atrophic changes with the use of topical corticosteroids.
Duration of treatment for children and infants: Courses should be limited if possible to five days and reviewed weekly. Occlusion should not be used.
Ointment: Bacterial infections are encouraged by warm, moist conditions induced by occlusive dressings, and so the skin should be cleansed before a fresh dressing is applied. Long-term continuous therapy should be avoided where possible, particularly in infants and children, as adrenal suppression can occur even without occlusion.

Pregnancy: Cream: There are limited data from the use of clobetasol in pregnant women.
Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development.
The relevance of this finding to humans has not been established. Administration of clobetasol during pregnancy should only be considered if the expected benefit to the mother outweighs the risk to the fetus. The minimum quantity should be used for the minimum duration.
Ointment: Clobetasol propionate ointment should not be used in pregnant women unless the potential benefit justifies the potential risk to the fetus.
Lactation: Cream: The safe use of topical corticosteroids during lactation has not been established.
It is not known whether the topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Administration of clobetasol during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant.
If used during lactation clobetasol should not be applied to the breasts to avoid accidental ingestion by the infant.
Ointment: It is not known whether topically applied Clobetasol propionate is secreted in breast milk. Caution should be exercised when Clobetasol propionate ointment is prescribed to nursing women.
Fertility: Cream: There are no data in humans to evaluate the effect of topical corticosteroids on fertility.
Clobetasol administered subcutaneously to rats had no effect upon mating performance; however, fertility was decreased at the highest dose.

Cream: Adverse drug reactions (ADRs) are listed as follows by MedDRA system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000) and very rare (<1/10,000), including isolated reports.
Post-marketing data: Infections and Infestations: Very rare: Opportunistic infection.
Immune System Disorders: Very rare: Hypersensitivity, generalised rash.
Endocrine Disorders: Very rare: Hypothalamicpituitary adrenal (HPA) axis suppression: Cushingoid features: (e.g. moon face, central obesity), delayed weight gain/growth retardation in children, osteoporosis, hyperglycaemia/glucosuria, hypertension, increased weight/obesity, decreased endogenous cortisol levels, alopecia, trichorrhexis.
Skin and Subcutaneous Tissue Disorders: Common: Pruritus, local skin burning/skin pain. Uncommon: Skin atrophy*, striae*, telangiectasias*. Very rare: Skin thinning*, skin wrinkling*, skin dryness*, pigmentation changes*, hypertrichosis, exacerbation of underlying symptoms, allergic contact dermatitis/dermatitis, pustular psoriasis, erythema, rash, urticaria, acne. Not known: Withdrawal reactions - redness of the skin which may extend to areas beyond the initial affected area, burning or stinging sensation, itch, skin peeling, oozing pustules.
*Skin features secondary to local and/or systemic effects of hypothalamic-pituitary adrenal (HPA) axis suppression.
General Disorders and Administration Site Conditions: Very rare: Application site irritation/pain.
Eye disorders: Very rare: Cataract, central serous chorioretinopathy, glaucoma. Not known (cannot be estimated from available data): Vision, blurred.
Ointment: Clobetasol ointment is usually well tolerated, but if signs of hypersensitivity appear, application should be stopped immediately.

Co-administered drugs that can inhibit CYP3A4 (e.g., ritonavir and itraconazole) have been shown to inhibit the metabolism of corticosteroids leading to increased systemic exposure. The extent to which this interaction is clinically relevant depends on the dose and route of administration of the corticosteroids and the potency of the CYP3A4 inhibitor.

Ointment: For external use only.

Store at temperatures not exceeding 30°C.

Topical Corticosteroids

D07AD01 - clobetasol ; Belongs to the class of very potent (group IV) corticosteroids. Used in the treatment of dermatological diseases.

Rx