Active ingredients: Clobetasol (clobetasol propionate)
CLOBESOL 0.05% Cream
CLOBESOL 0.05% Ointment
Why is Clobesol used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Very active corticosteroids (group IV)
THERAPEUTIC INDICATIONS
Skin diseases sensitive to corticosteroids, especially the more demanding and resistant ones such as, for example, psoriasis (excluding diffuse plaque psoriasis), recurrent eczema, lichen planus and discoid lupus erythematosus and all other conditions that do not respond satisfactorily to less active steroids.
Due to its therapeutic characteristics, clobetasol propionate is able to quickly resolve even dermatological lesions resistant to other corticosteroids. After treatment with Clobesol, relapsing skin diseases generally have longer remission times and less severe relapses.
Contraindications When Clobesol should not be used
- Hypersensitivity to the active substance, to any of the excipients or to other closely related substances from a chemical point of view The following diseases should not be treated with clobetasol propionate: untreated skin infections
- Primary viral skin infections to be treated (herpes, chicken pox, etc.)
- Primary bacterial or fungal infections of the skin
- Rosacea
- Acne vulgaris
- Perioral dermatitis
- Skin ulcers
- Itching without inflammation
- Anogenital itching
- Dermatosis in infants less than 1 year of age including dermatitis and diaper rash.
Occlusive dressing is contraindicated in exudative lesions and in patients with atopic dermatitis. Generally contraindicated during pregnancy and contraindicated during lactation. The product is not for ophthalmic use.
Precautions for use What you need to know before taking Clobesol
Clobetasol propionate should be used with caution in patients with a history of local hypersensitivity to corticosteroids or to any of the excipients of the drug. Local hypersensitivity reactions (see Side Effects) may resemble symptoms of the disease being treated.
In some individuals, manifestations of hypercortisolism (Cushing's syndrome) and reversible suppression of the hypothalamic-pituitary-adrenal axis (HPA), leading to glucocorticoid insufficiency, may occur due to the "increased systemic absorption" of topical steroids. observed one of the above effects, the application of the drug should be gradually reduced by decreasing the frequency of applications or by replacing it with a less potent corticosteroid. Abrupt discontinuation of treatment may lead to glucocorticosteroid insufficiency (see Side Effects).
The risk factors for increased systemic effects are:
- Topical steroid potency and formulation
- Duration of exposure
- Application on a large surface area
- Use on occluded areas of skin for example on intertriginous areas or under occlusive dressing (in children the diaper can act as an occlusive dressing)
- Increased hydration of the stratum corneum
- Use on thin skin areas such as the face
- Use on non-intact skin or in other conditions where the skin barrier may be damaged
- Compared to adults, children can absorb proportionally more topical corticosteroids and thus be more susceptible to systemic side effects. This is due to the fact that children have an immature skin barrier and a higher surface area to body weight ratio than adults.
Children
In infants and children under the age of 12, continuous, long-term therapy with topical corticosteroids should be avoided where possible, as suppression of adrenal activity is more likely to occur.
Children are more likely to develop atrophic changes with the use of topical corticosteroids. If the use of clobetasol propionate is necessary in children, it is recommended that treatment should be limited to only a few days and be reviewed weekly.
Risk of infection in case of occlusion
Hot humid conditions in skin folds or those caused by occlusive dressing promote bacterial infections. If an occlusive dressing is used, the skin surface must be thoroughly cleansed before each renewal of the dressing.
Psoriasis
Topical corticosteroids should be used with caution in psoriasis because rebound relapses, development of tolerance, risk of generalized pustular psoriasis and development of local or systemic toxicity due to impaired skin barrier function have been reported in some cases.Therefore, if topical steroids are used in psoriasis it is important to monitor the patient closely.
Superinfections
In the case of superinfection of inflammatory lesions, "appropriate antimicrobial therapy is required. If the infection spreads, it is necessary to discontinue topical corticosteroid therapy and administer" appropriate antibacterial therapy.
Chronic leg ulcers
In some cases, topical corticosteroids are used to treat dermatitis near chronic leg ulcers. However, this use may be associated with a higher frequency of local hypersensitivity reactions and an increased risk of local infections.
Application on the face
Prolonged application on the face is not recommended as this area of the body is more susceptible to atrophic changes than other skin areas. If the drug is used on the face, treatment should be limited to only a few days.
Application on the eyelids
If the drug is applied to the eyelids, extreme caution should be used to ensure that the drug does not get into the eye, as prolonged exposure could cause cataracts and glaucoma.
If the occlusive bandage is used, the skin surface must be well washed before each renewal of the occlusive bandage, to avoid bacterial infections, which are easy to occur in the warm humid environment induced by the occlusion.
In occlusive treatments it should be borne in mind that the films used for the bandage can themselves cause sensitization phenomena. Patients should be advised to wash their hands after applying Clobesol unless the treatment involves the hands themselves.
Interactions Which drugs or foods can modify the effect of Clobesol
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Co-administration of drugs that can inhibit CYP3A4 (eg ritonavir and itraconazole) has been shown to inhibit the metabolism of corticosteroids resulting in 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.
Warnings It is important to know that:
Ask your doctor or pharmacist for advice before taking any medicine.
Fertility
There are no human data to evaluate the effect of topical corticosteroids on fertility.
Pregnancy
There are limited data on the use of clobetasol propionate in pregnant women.
Topical administration of corticosteroids during pregnancy in laboratory animals can cause abnormalities in fetal development. The relevance of this experimental finding has not been established in humans. Administration of clobetasol propionate during pregnancy should only be considered if the expected benefit to the mother outweighs any possible risk to the fetus. The minimum amount should be used for as little time as possible.
Feeding time
It has not been established whether the use of topical corticosteroids while breastfeeding is safe.
It is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities of the active substance in breast milk.
Topical administration of clobetasol propionate during lactation should only be considered if the expected benefit to the mother outweighs the risk to the baby.
If used during breastfeeding, clobetasol propionate should not be applied to the breast to avoid accidental ingestion by the baby.
Effects on ability to drive and use machines
No studies have been performed to investigate the effect of clobetasol propionate on the ability to drive and use machines. An adverse effect on these activities would not be expected given the side effect profile of topical clobetasol propionate.
Important information about some of the ingredients
Clobesol cream and Clobesol ointment contain propylene glycol which can cause skin irritation.
Clobesol cream contains cetostearyl alcohol which can cause local skin reactions (such as contact dermatitis) and chlorocresol which can cause allergic reactions.
Dosage and method of use How to use Clobesol: Dosage
Ointment - Dry scaly dermatoses with a lichenoid and hyperkeratotic imprint are most affected by the application of the ointment.
Cream - The application of the cream is indicated in all lesions at any location. The water-dispersible vehicle makes the cream preferable in the treatment of delicate and moist skin surfaces.
Adults, the elderly and children aged one year and over
Apply and gently massage a thin layer of product sufficient to cover the entire affected area 1 or 2 times a day for up to 4 weeks until a significant improvement is obtained, then reduce the frequency of applications or switch to a less potent cortisone. allow sufficient time for absorption after each application before applying the emollient cream. Control of exacerbations can be achieved with repeated short courses of treatment with clobetasol propionate.
In more resistant lesions, especially in the case of hyperkeratosis, the effect of clobetasol can be enhanced, if necessary, by means of an occlusive bandage with polyethylene films; this bandage, maintained only during the night, allows to obtain a satisfactory response; subsequently the improvement it can also be maintained without an occlusive dressing.
If conditions worsen or do not clear up in 2-4 weeks, treatment and diagnosis should be reassessed.
Treatment should not be continued for more than 4 weeks without medical supervision. If continued steroid therapy is required, a less potent preparation should be used.
The maximum weekly dose must not exceed 50g per m2 / week.
Atopic dermatitis (eczema)
Clobetasol propionate therapy should be gradually discontinued once disease control is achieved and an emollient cream should be used as maintenance therapy. Relapses of pre-existing dermatitis can occur with abrupt discontinuation of clobetasol propionate.
Recurrent eczema
Once an acute episode has been effectively treated following continued topical corticosteroid therapy, intermittent dosing (once daily, twice weekly, without occlusive dressing) should be considered. This process has been shown to be useful in reducing the frequency of relapses.
The application must be continued on all the previously treated areas and also on those known as sites of possible relapses. This regimen must be associated with the daily use of emollients. The condition and the benefit / risk ratio of continued treatment should be reassessed on a regular basis.
Pediatric population
Clobetasol propionate is contraindicated in children under 1 year of age. Children are more likely to develop local and systemic side effects of topical corticosteroids and, in general, require shorter and less potent cortisone therapies than adults.
Care should be taken when using clobetasol propionate to ensure that the amount of drug required is the minimum that provides therapeutic benefit.
Elderly population
Clinical trials have identified no differences in drug responses between older and younger patients. The higher frequency of cases of decreased hepatic or renal function in elderly patients may delay elimination if systemic absorption occurs. Therefore the minimum amount of drug should be used and for the shortest time to achieve the desired clinical benefit. .
Renal / hepatic insufficiency
In case of systemic absorption (when the application is over a large surface for a prolonged period), metabolism and elimination may be slowed thus causing an increased risk of systemic toxicity. Therefore the minimum amount of medication and for the shortest time to achieve the desired clinical benefit.
Overdose What to do if you have taken too much Clobesol
Symptoms and signs:
Topically applied clobetasol propionate can be absorbed in sufficient quantity to give systemic effects.
Acute overdose is very unlikely, however in the event of chronic overdose or abuse, signs of hypercortisolism may occur (see Undesirable Effects).
The excessive and prolonged use of topical corticosteroids can depress the adrenal pituitary function, causing secondary hypoadrenalism and manifestations of hypercortisolism including Cushing's syndrome, in particular asthenia, adynamia, arterial hypertension, heart rhythm disturbances, hypokalemia, metabolic acidosis.
Treatment:
In the event of an overdose, the application of clobetasol propionate should be discontinued gradually by reducing the frequency of applications or by replacing the drug with a less potent corticosteroid to avoid the risk of adrenal insufficiency.
Further medical evaluation should be undertaken as clinically indicated or as recommended by the National Poisons Center, if available.
Symptoms of acute hypercorticalism are usually reversible. If necessary, treat the electrolyte imbalance.
In case of accidental ingestion / intake of an excessive dose of Clobesol, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Clobesol, ask your doctor or pharmacist.
Side Effects What are the side effects of Clobesol
Like all medicines, Clobesol can cause side effects, although not everybody gets them.
Side effects are listed below by MedRA organ / system, class and frequency. Frequencies are defined as: very common (> 1/10), common (> 1/100 and 1/1000 and 1 / 10,000 and <1/1000) and very rare (<1 / 10,000) including isolated reports.
Data after marketing
Infections and infestations
Very rare: opportunistic infections
Disorders of the immune system
Very rare: local hypersensitivity
Endocrine pathologies
Very rare: suppression of the hypothalamic-pituitary-adrenal axis (HPA): Cushingoid features (e.g. face-to-face, mid-body obesity); weight gain / growth retardation in children; osteoporosis; glaucoma; hyperglycemia / glucosuria; cataract; hypertension; weight gain / obesity; decrease in endogenous cortisol levels; alopecia; trichoresis
Skin and subcutaneous tissue disorders
Common: pruritus, local skin burning / skin pain
Uncommon: skin atrophy *, striae *, telangiectasia *
Very rare: skin thinning *, skin wrinkling *, dry skin *, pigmentation changes *, hypertrichosis, exacerbation of pre-existing symptoms, allergic contact dermatitis / dermatitis, pustular psoriasis; erythema; rash; urticaria * Skin characteristics secondary to local and / or systemic effects of suppression of the hypothalamic-pituitary-adrenal axis (HPA).
General disorders and administration site conditions
Very rare: application site irritation / pain
Compliance with the instructions in the package leaflet reduces the risk of side effects.If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Conservation rules
Store at a temperature not exceeding 30 ° C. The cream must not be diluted.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children.
Composition and pharmaceutical form
COMPOSITION
CLOBESOL 0.05% Cream - 100 g contain: clobetasol propionate 0.050 g Excipients: propylene glycol, self-emulsifying glyceryl monostearate, glyceryl monostearate, cetostearyl alcohol, mixture of paraffins and natural waxes, chlorocresol, sodium citrate, citric acid, purified water
CLOBESOL 0.05% Ointment - 100 g contain: clobetasol propionate 0.050 g Excipients: propylene glycol, sorbitan sesquioleate, white petroleum jelly
PHARMACEUTICAL FORM AND CONTENT
Cream: 30 g tube. Ointment: 30 g tube
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CLOBESOL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
0.05% Cream
100 g contain: clobetasol propionate 0.050 g.
0.05% Ointment
100 g contain: clobetasol propionate 0.050 g.
03.0 PHARMACEUTICAL FORM
Cream.
Ointment.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Skin diseases sensitive to corticosteroids, especially the more demanding and resistant ones such as, for example, psoriasis (excluding diffuse plaque psoriasis), recurrent eczema, lichen planus and discoid lupus erythematosus and all other conditions that do not respond satisfactorily to less active steroids.
Due to its therapeutic characteristics, clobetasol propionate is able to quickly resolve even dermatological lesions resistant to other corticosteroids. After treatment with Clobesol, relapsing skin diseases generally have longer remission times and less severe relapses.
04.2 Posology and method of administration
Ointment
Dry scaly dermatoses with a lichenoid and hyperkeratotic imprint are most affected by the application of the ointment.
Cream
The application of the cream is indicated in all lesions at any location. The hydrodispersible vehicle makes the cream preferable in the treatment of delicate and moist skin surfaces.
Adults, the elderly and children aged one year and over
Apply and gently massage a thin layer of product sufficient to cover the entire affected area 1 or 2 times a day for up to 4 weeks until a significant improvement is obtained, then reduce the frequency of applications or switch to a less potent cortisone. allow sufficient time for absorption after each application before applying the emollient cream.
Control of exacerbations can be achieved with repeated short courses of treatment with clobetasol propionate.
In more resistant lesions, especially in the case of hyperkeratosis, the effect of clobetasol can be enhanced, if necessary, by means of an occlusive bandage with polyethylene films; this bandage, maintained only during the night, allows to obtain a satisfactory response; subsequently the improvement it can also be maintained without an occlusive dressing.
If conditions worsen or do not clear up in 2-4 weeks, treatment and diagnosis should be reassessed.
Treatment should not be continued for more than 4 weeks without medical supervision. If continued steroid therapy is required, a less potent preparation should be used.
The maximum weekly dose must not exceed 50g per m2 / week.
Atopic dermatitis (eczema)
Clobetasol propionate therapy should be gradually discontinued once disease control is achieved and an emollient cream should be used as maintenance therapy. Relapses of pre-existing dermatitis can occur with abrupt discontinuation of clobetasol propionate.
Recurrent eczema
Once an acute episode has been effectively treated following continued topical corticosteroid therapy, intermittent dosing (once daily, twice weekly, without occlusive dressing) should be considered. This process has been shown to be useful in reducing the frequency of relapses.
The application must be continued on all the previously treated areas and also on those known as sites of possible relapses. This regimen must be associated with the daily use of emollients. The condition and the benefit / risk ratio of continued treatment should be reassessed on a regular basis.
Pediatric population
Clobetasol propionate is contraindicated in children under one year of age.
Children are more likely to develop the local and systemic side effects of topical corticosteroids and, in general, require shorter and less potent corticosteroid therapies than adults.
Care should be taken when using clobetasol propionate to ensure that the amount of drug required is the minimum that provides therapeutic benefit.
Elderly population
Clinical trials have identified no differences in drug responses between older and younger patients. The higher frequency of cases of decreased hepatic or renal function in elderly patients may delay elimination if systemic absorption occurs. Therefore the minimum amount of drug should be used and for the shortest time to achieve the desired clinical benefit. .
Renal / hepatic insufficiency
In case of systemic absorption (when the application is over a large surface for a prolonged period), metabolism and elimination may be slowed thus causing an increased risk of systemic toxicity. Therefore the minimum amount of medication and for the shortest time to achieve the desired clinical benefit.
04.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients or to other closely related substances from a chemical point of view.
The following conditions should not be treated with clobetasol propionate:
• untreated skin infections
• primary viral infections of the skin to be treated (herpes, chicken pox, etc.)
• primary bacterial or fungal infections of the skin
• rosacea
• acne vulgaris
• perioral dermatitis
• skin ulcers
• itching without inflammation
• anogenital itching
• dermatosis in infants less than 1 year of age including dermatitis and diaper rash
Occlusive dressing is contraindicated in exudative lesions and in patients with atopic dermatitis.
Contraindicated during pregnancy and lactation (see section 4.6).
The product is not for ophthalmic use.
04.4 Special warnings and appropriate precautions for use
Clobetasol propionate should be used with caution in patients with a history of local hypersensitivity to corticosteroids or to any of the excipients of the drug. Local hypersensitivity reactions (see section 4.8)) may resemble symptoms of the disease being treated.
In some individuals, manifestations of hypercortisolism (Cushing's syndrome) and reversible suppression of the hypothalamic-pituitary-adrenal axis (HPA), leading to glucocorticoid insufficiency, may occur due to the "increased systemic absorption" of topical steroids. observed one of the above effects, the application of the drug should be gradually reduced by decreasing the frequency of applications or by replacing it with a less potent corticosteroid. Abrupt discontinuation of treatment may lead to glucocorticosteroid insufficiency (see section 4.8).
The risk factors for increased systemic effects are:
• potency and formulation of the topical steroid
• duration of exposure
• application on a large surface area
• use on occluded areas of skin, for example on intertriginous areas or under occlusive dressing (in children the diaper can act as an occlusive dressing)
• increased hydration of the stratum corneum
• use on thin skin areas such as the face
• use on skin that is not intact or in other conditions where the skin barrier can be damaged
• Compared to adults, children may absorb proportionally more topical corticosteroids and thus be more susceptible to systemic side effects. This is due to the fact that children have an immature skin barrier and a higher surface area to body weight ratio than adults.
Children
In infants and children under the age of 12, continuous, long-term therapy with topical corticosteroids should be avoided where possible, as suppression of adrenal activity is more likely to occur.
Children are more likely to develop atrophic changes with the use of topical corticosteroids. If the use of clobetasol propionate is necessary in children, it is recommended that treatment should be limited to only a few days and be reviewed weekly.
Risk of infection in case of occlusion
Hot humid conditions in skin folds or those caused by occlusive dressing promote bacterial infections. If an occlusive dressing is used, the skin surface must be thoroughly cleansed before each renewal of the dressing.
Psoriasis
Topical corticosteroids should be used with caution in psoriasis because rebound relapses, development of tolerance, risk of generalized pustular psoriasis and development of local or systemic toxicity due to impaired skin barrier function have been reported in some cases. Therefore, if topical steroids are used in psoriasis it is important to monitor the patient closely.
Superinfections
In the case of superinfection of inflammatory lesions, "appropriate antimicrobial therapy is required. If the infection spreads, it is necessary to discontinue topical corticosteroid therapy and administer" appropriate antibacterial therapy.
Chronic leg ulcers
In some cases, topical corticosteroids are used to treat dermatitis near chronic leg ulcers. However, this use may be associated with a higher frequency of local hypersensitivity reactions and an increased risk of local infections.
Application on the face
Prolonged application on the face is not recommended as this area of the body is more susceptible to atrophic changes than other skin areas.
If the drug is used on the face, treatment should be limited to only a few days.
Application on the eyelids
If the drug is applied to the eyelids, extreme caution should be used to ensure that the drug does not get into the eye, as prolonged exposure could cause cataracts and glaucoma.
If the occlusive bandage is used, the skin surface must be well washed before each renewal of the occlusive bandage, to avoid bacterial infections, which are easy to occur in the warm humid environment induced by the occlusion.
In occlusive treatments it should be borne in mind that the films used for the bandage can themselves cause sensitization phenomena.
Patients should be advised to wash their hands after applying Clobesol unless the treatment involves the hands themselves.
Clobesol cream and Clobesol ointment contain propylene glycol which can cause skin irritation.
Clobesol cream contains cetostearyl alcohol which can cause local skin reactions (such as contact dermatitis) and chlorocresol which can cause allergic reactions.
04.5 Interactions with other medicinal products and other forms of interaction
Co-administration of drugs that can inhibit CYP3A4 (eg ritonavir and itraconazole) has been shown to inhibit the metabolism of corticosteroids resulting in 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.
04.6 Pregnancy and lactation
Fertility
There are no human data to evaluate the effect of topical corticosteroids on fertility.
Pregnancy
There are limited data on the use of clobetasol propionate in pregnant women.
Topical administration of corticosteroids during pregnancy in laboratory animals may cause abnormalities in fetal development (see section 5.3). The relevance of this experimental finding has not been established in humans. Administration of clobetasol propionate during pregnancy should only be considered if the expected benefit to the mother outweighs any possible risk to the fetus. The minimum amount should be used for as little time as possible.
Feeding time
It has not been established whether the use of topical corticosteroids while breastfeeding is safe.
It is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities of the active substance in breast milk.
Topical administration of clobetasol propionate during lactation should only be considered if the expected benefit to the mother outweighs the risk to the baby.
If used during breastfeeding, clobetasol propionate should not be applied to the breast to avoid accidental ingestion by the baby.
04.7 Effects on ability to drive and use machines
No studies have been performed to investigate the effect of clobetasol propionate on the ability to drive and use machines. An adverse effect on these activities would not be expected given the side effect profile of topical clobetasol propionate.
04.8 Undesirable effects
Undesirable effects are listed below by organ / system, MedRA class and frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 and
Data after marketing
Infections and infestations
Very rare: opportunistic infections.
Disorders of the immune system
Very rare: local hypersensitivity.
Endocrine pathologies
Very rare: suppression of the hypothalamus-pituitary-adrenal (HPA) axis: Cushingoid features (e.g. face-to-face, mid-body obesity); weight gain / growth retardation in children; osteoporosis; glaucoma; hyperglycemia / glycosuria; cataracts; hypertension; weight gain / obesity; decrease in endogenous cortisol levels; alopecia; tricorrhesis.
Skin and subcutaneous tissue disorders
Common: pruritus, local skin burning / skin pain.
Uncommon: skin atrophy *, striae *, telangiectasia *.
Very rare: skin thinning *, skin wrinkling *, dry skin *, pigmentation changes *, hypertrichosis, exacerbation of pre-existing symptoms, allergic contact dermatitis / dermatitis, pustular psoriasis; erythema; rash; urticaria.
* Skin characteristics secondary to local and / or systemic effects of suppression of the hypothalamic-pituitary-adrenal axis (HPA).
General disorders and administration site conditions
Very rare: application site irritation / pain.
04.9 Overdose
Symptoms and signs
Topically applied clobetasol propionate can be absorbed in sufficient quantity to give systemic effects.
Acute overdose is very unlikely, however in the event of chronic overdose or abuse, signs of hypercortisolism may occur (see section 4.8).
The excessive and prolonged use of topical corticosteroids can depress the adrenal pituitary function, causing secondary hypoadrenalism and manifestations of hypercortisolism including Cushing's syndrome, in particular asthenia, adynamia, arterial hypertension, heart rhythm disturbances, hypokalemia, metabolic acidosis.
Treatment
In the event of an overdose, the application of clobetasol propionate should be discontinued gradually by reducing the frequency of applications or by replacing the drug with a less potent corticosteroid to avoid the risk of adrenal insufficiency.
Further medical evaluation should be undertaken as clinically indicated or as recommended by the National Poisons Center, if available.
Symptoms of acute hypercorticalism are usually reversible. If necessary, treat the electrolyte imbalance.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: very active corticosteroids (group IV).
ATC code: D07AD01
Topical corticosteroids act as anti-inflammatory agents through a multiple mechanism aimed at inhibiting delayed phase allergic reactions which include decreased mast cell density, decreased chemotaxis and activation of eosinophils, decreased cytokine production by lymphocytes, monocytes, mast cells and eosinophils and inhibition of arachidonic acid metabolism.
Pharmacodynamic effects
Topical corticosteroids have anti-inflammatory, antipruritic and vasoconstrictive properties.
Clobesol contains a corticosteroid (clobetasol propionate), synthesized by the researches of the GlaxoSmithKline Group, which has been shown to have a high topical activity through the McKenzie "vasoconstriction test", confirmed in the clinic during numerous trials.
The systemic activity of the steroid is as follows:
• clobetasol propionate is always more active than the alcohol betamethasone mouse thymolysis test regardless of the vehicle and route of administration; in particular, the compound, compared to the standard, is 2 times more potent orally, and 11 times subcutaneously;
• clobetasol propionate was shown to be 5 times more active than alcohol betamethasone in test of anti-granulomatous activity in mice;
• In the rat the anti-inflammatory activity of clobetasol propionate studied by cotton pellet thymolysis and granuloma test, is similar or inferior to that of betamethasone depending on the route of administration.
Clobetasol propionate is devoid of estrogenic, androgenic and anabolic activity in both mice and rats and of antigonadotropic activity in rats.
Clobetasol propionate demonstrated anti-estrogenic activity in both mice and rats.
In rabbits it has progestogenic activity higher than or equal to that of progesterone (respectively by subcutaneous and oral route); its activity is comparable to that of fluocinolone 16-17 acetonide.
The topical activity has been studied in man using the vasoconstriction test. The vasoconstriction index of clobetasol propionate was equal to 1869, assuming the activity of fluocinolone acetonide equal to 100.
05.2 Pharmacokinetic properties
Absorption
Topical corticosteroids can be absorbed systemically through intact skin. The level of percutaneous absorption of topical corticosteroids is determined by several factors, including the vehicle and the integrity of the skin barrier. Occlusion, inflammation and / or other pathological processes of the skin may also increase percutaneous absorption.
In the epicutaneous absorption tests in dogs with treatments for 10 days at high doses (0.1 g / kg, corresponding in a man of 70 kg to 35 mg of active principle), there was no modification of the adrenal activity, assessed by determining plasma cortisol levels.
The variation of cortisolemia expresses the possible systemic passage: the extent of this passage is correlated to the extension of the treated surface, to the degree of alteration of the epidermis, to the duration of the treatment.
There was a mean peak plasma concentration of clobetasol propionate of 0.63 nanograms / ml in a study conducted eight hours after the second application (13 hours after the first initial application) of 30 g of clobetasol propionate ointment at the 0.05% applied to normal individuals with healthy skin. After the application of a second dose of 30 g of 0.05% clobetasol propionate cream, the mean peak plasma concentrations were slightly higher than those of the ointment and occurred 10 hours after application. In a separate study, mean peak plasma concentrations of approximately 2.3 nanograms / mL and 4.6 nanograms / mL occurred in patients with psoriasis and eczema, respectively, three hours after a single application of 25 g of base ointment. 0.05% clobetasol propionate.
Distribution
The use of pharmacodynamic endpoints to assess the systemic exposure of topical corticosteroids is necessarily due to the fact that the circulating levels are well below the level of detection.
Metabolism
Once absorbed through the skin, topical corticosteroids are metabolised via pharmacokinetic pathways similar to those of systemically administered corticosteroids. The latter are mainly metabolised in the liver.
Elimination
Topical corticosteroids are eliminated by the kidneys. In addition, some corticosteroids and their metabolites are also excreted via the bile.
05.3 Preclinical safety data
Carcinogenesis / Mutagenesis
Carcinogenesis
Long-term animal studies have not been performed to evaluate the carcinogenic potential of topical clobetasol propionate.
Genotoxicity
Clobetasol propionate was not shown to be mutagenic in a series of in vitro assays of bacterial cells.
Reproductive toxicology
Fertility
The effect of topical clobetasol propionate on fertility in animals has not been evaluated.
Pregnancy
Subcutaneous administration of clobetasol propionate in mice (≥100 mcg / kg / day), rats (400 mcg / kg / day) or rabbits (1 to 10 mcg / kg / day) during pregnancy resulted in fetal abnormalities including cleft palate.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Cream
Propylene glycol, self-emulsifying glyceryl monostearate, glyceryl monostearate, cetostearyl alcohol, mixture of paraffins and natural waxes, chlorocresol, sodium citrate, citric acid, purified water.
Ointment
Propylene glycol, sorbitan sesquioleate, white petroleum jelly.
06.2 Incompatibility
No incompatibilities with other drugs have been identified.
06.3 Period of validity
Cream: 24 months.
Ointment: 24 months.
06.4 Special precautions for storage
Store at a temperature not exceeding 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
CLOBESOL 0.05% Cream
The product is packaged in painted aluminum tubes with a polyethylene screw cap.
CLOBESOL 0.05% Ointment
The product is packaged in painted aluminum tubes with a polyethylene screw cap.
Cream - tube 30 g
Ointment - tube 30 g
06.6 Instructions for use and handling
The cream must not be diluted.
07.0 MARKETING AUTHORIZATION HOLDER
GlaxoSmithKline S.p.A., Via A. Fleming, 2 - Verona
08.0 MARKETING AUTHORIZATION NUMBER
CLOBESOL 0.05% Cream - 1 tube of 30 g - A.I.C. 023639026
CLOBESOL 0.05% Ointment - 1 tube of 30 g - A.I.C. 023639040
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
23 August 1978 / May 2010
10.0 DATE OF REVISION OF THE TEXT
November 22, 2012
