Instructions Advantan cream 0.1% tube 15 g
Composition
active ingredient: methylprednisolone aceponate;
1 g of cream contains 1 mg of methylprednisolone aceponate;
excipients: decyl oleate, glycerol monostearate 40-55%, cetostearyl alcohol, hard fat, softizan-378, polyoxyl-40-stearate, glycerol 85%, sodium edetate, benzyl alcohol, butylhydroxytoluene, purified water.
Dosage form
Cream.
Main physicochemical properties: white opaque cream.
Pharmacotherapeutic group
Corticosteroids for use in dermatology.
ATX code D07A C14.
Pharmacological properties
Pharmacodynamics.
Advantan®, when applied topically, suppresses inflammatory and allergic skin reactions, as well as reactions associated with cell hyperproliferation, which helps eliminate both objective symptoms (erythema, edema, maceration) and subjective complaints (itching, burning, pain).
Methylprednisolone aceponate is known to bind directly to intracellular glucocorticoid receptors. This is especially true for the main metabolite, 6α-methylprednisolone-17-propionate, which is formed after cleavage in the skin.
Binding of the receptor-steroid complex to a specific region of the DNA molecule initiates a number of biological effects.
Binding of the receptor-steroid complex leads to the induction of macrocortin synthesis. Macrocortin inhibits the release of arachidonic acid and thus reduces the formation of inflammatory mediators such as prostaglandins and leukotrienes.
The immunosuppressive effect of glucocorticosteroids can be explained by inhibition of cytokine synthesis and an antimitotic effect, which is not yet well understood.
Inhibition of the synthesis of vasodilating prostaglandins or potentiation of the vasoconstrictor effect of adrenaline ultimately determines the vasoconstrictor activity of glucocorticosteroids.
Methylprednisolone aceponate (6a-methylprednisolone aceponate) is a non-halogenated corticosteroid synthetic molecule characterized by an increased degree of dissociation during the implementation of its local and systemic action.
The 6a-methyl group has a potentiating effect, and the lipophilic ester groups provide better penetration through the skin.
The local anti-inflammatory effect, confirmed by pharmacological and clinical-pharmacological studies, is similar to the effect of more potent corticosteroids. The systemic effect of methylprednisolone aceponate when applied topically, according to studies, is expressed to a minor extent.
Pharmacokinetics.
Methylprednisolone aceponate is hydrolyzed in the epidermis and dermis to form 6a-methylprednisolone-17-propionate, its major metabolite, which binds more strongly to corticosteroid receptors than the parent product, a clear indication of cutaneous bioactivation.
The percentage and total rate of transdermal absorption of a topical corticosteroid depends on a number of factors, such as the chemical structure of the compound, excipients, concentration of the compound in the base, conditions of action (surface area treated, duration of action, open or occlusive treatment method), and skin characteristics (type and severity of pathology, anatomical localization).
The percutaneous absorption of methylprednisolone aceponate in the form of a cream was studied in healthy volunteers. When occlusive dressings of 15 g of Advantan® cream were applied twice daily for 7 days, the average percutaneous absorption was approximately 2.5%, which corresponds to a systemic corticosteroid load of approximately 10 μg/kg/day. The percutaneous absorption of methylprednisolone aceponate was significantly increased when the skin was damaged experimentally by removing the stratum corneum of the epidermis.
Once in the bloodstream, the main hydrolysis product of methylprednisolone aceponate, 6a-methylprednisolone-17-propionate, is rapidly conjugated with glucuronic acid and thus inactivated.
Metabolites of methylprednisolone aceponate (the main metabolite is 6a-methylprednisolone-17-propionate-21-glucuronide) are excreted from the body mainly in the urine, the half-life is approximately 16 hours. After intravenous administration, complete excretion in the urine and feces occurs within 7 days. Cumulation of the active substance or metabolites in the body is not observed.
Indication
Atopic dermatitis (neurodermatitis, endogenous eczema); true eczema; simple contact dermatitis and allergic contact dermatitis; dyshidrotic eczema, infantile eczema.
Contraindication
Hypersensitivity to methylprednisolone aceponate or to any other component of the drug; tuberculous and syphilitic processes in the area of application of the drug; viral diseases (e.g. chickenpox, shingles), rosacea, perioral dermatitis, ulcerative skin lesions, acne vulgaris, atrophic dermatitis, skin reactions after vaccination in the area of application of the drug; skin diseases accompanied by bacterial or fungal infections (see section "Special instructions").
Interaction with other medicinal products and other types of interactions
Due to absorption, treatment of large areas of skin or treatment over a long period of time may cause interactions similar to those seen with systemic therapy. However, none of these interactions have been reported to date.
If it is necessary to use any other medicines at the same time, you should consult a doctor.
Application features
Glucocorticoids should be used only in the lowest possible doses, especially in children, and only for the period when it is absolutely necessary to achieve and maintain the desired therapeutic effect.
When treating a pathological process on a large area of skin, the duration of therapy should be clearly determined by the doctor.
In case of bacterial skin infections and/or fungal lesions, additional special treatment with antibacterial and/or antimycotic drugs is necessary.
Local skin infections may be exacerbated by topical glucocorticoids.
It is necessary to avoid using the drug on the face in case of rosacea or perioral dermatitis.
When using the drug Advantan®, avoid getting the drug in the eyes, deep open wounds, or mucous membranes.
When methylprednisolone aceponate (Advantan® 0.1% hydrophobic cream) was applied to 60% of the body surface under an occlusive dressing for 22 hours in healthy adult volunteers, a decrease in plasma cortisol levels and an effect on its circadian rhythm were observed. This regimen of drug administration should be used as little as possible. When applying Advantan® to a large surface of the skin (40-90% of the skin surface) without the use of occlusion in children (in newborns, the function of the occlusive dressing can be performed by a diaper), no impairment of the function of the adrenal cortex was observed. Despite this, when applying the drug to a large surface of the skin, the duration of treatment should be as short as possible.
The risk of side effects is significantly increased when topical corticosteroids are applied to large areas of the body or for prolonged periods, especially under occlusive dressings. Treatment with occlusive dressings should be avoided unless indicated. It should be remembered that diapers and nappies, as well as diaper rash, can have the same effect as occlusive dressings.
When treating large areas of the body surface, the duration of treatment should be as short as possible, as the possibility of absorption or systemic effects cannot be completely ruled out.
As with all corticosteroids, inappropriate use of this medicinal product may mask clinical symptoms.
If the skin becomes excessively dry with prolonged application of Advantan® cream, it is recommended to switch to another dosage form of the drug with a higher fat content (Advantan® ointment or Advantan® fatty ointment).
As with systemic corticosteroids, glaucoma may occur with topical use (e.g., after application in high doses or to large surfaces for a prolonged period, when using occlusive dressings, or when applied to the skin around the eyes).
Prolonged use of topical medications may cause sensitization. In such cases, therapy should be discontinued and appropriate treatment instituted.
The preparation contains cetostearyl alcohol, butylhydroxytoluene, which may cause the development of local skin reactions such as contact dermatitis; butylhydroxytoluene may cause irritation of the eyes and mucous membranes.
Use during pregnancy or breastfeeding
There are currently no reliable data on the use of Advantan® in pregnant women, however, minimal risk is expected, since the likelihood of systemic effects of topical corticosteroids is very low.
Experimental studies in animals using methylprednisolone aceponate at doses exceeding the therapeutic dose have revealed embryotoxic and/or teratogenic effects.
Pregnant or breastfeeding women should not use this medication unless absolutely necessary and without close medical supervision.
In the 1st trimester of pregnancy, it is advisable to avoid external use of preparations containing corticosteroids. During pregnancy, treatment of large areas of skin, long-term use of the preparation or its use under an occlusive dressing should be avoided.
Some epidemiological studies suggest an increased risk of cleft palate in newborns whose mothers received corticosteroid treatment during the first trimester of pregnancy.
Studies in mice have shown that methylprednisolone aceponate does not pass into breast milk. However, it is not known whether methylprednisolone aceponate passes into human breast milk, since corticosteroids administered systemically have been present in human breast milk. It is not known whether topical application of Advantan® cream would result in systemic absorption of methylprednisolone aceponate in amounts that would be detectable in human breast milk. Therefore, caution should be exercised when administering Advantan® cream to nursing women.
During breastfeeding, the drug should not be applied to the mammary glands. In particular, prolonged use of the drug, its application to large areas of skin, or its use under an occlusive dressing should be avoided.
There is no information on the effect of methylprednisolone aceponate on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Not installed.
Method of administration and doses
Usually, the drug should be applied to the affected areas of the skin once a day in a thin layer, unless otherwise prescribed by a doctor.
The formula of Advantan® cream (1 g of Advantan® cream contains 1 mg of methylprednisolone aceponate) due to its high water content ensures the outflow of exudate and is therefore particularly suitable for the treatment of weeping eczematous elements in the acute phase, as well as macerated skin areas, whether or not covered with hair.
The duration of use in normal cases should not exceed 12 weeks for adults and 4 weeks for children. There is no data on the safety of using Advantan® cream in children under 4 months of age.
When using Advantan® cream to treat children aged 4 months and older, there is no need for dose adjustment.
Children.
There is no data on the safety of using Advantan® cream in children under 4 months of age. It is recommended to consult a doctor before using it in children aged 4 months to 3 years.
When using Advantan® cream to treat children aged 4 months and older, there is no need for dose adjustment.
The duration of use in children should not normally exceed 4 weeks.
Advantan® cream should not be used on children under an occlusive dressing. It should be remembered that diapers and nappies can have the same effect as an occlusive dressing.
Overdose
In cases of cutaneous atrophoderma associated with overdose in the case of topical application of the drug, treatment should be discontinued. As a rule, symptoms regress within 10-14 days.
The results of acute toxicity studies with methylprednisolone aceponate have not revealed any risk of acute intoxication after a single application of excessive amounts of the drug to the skin (application to a large body surface area under conditions conducive to absorption) or after accidental ingestion.
Side effects
During clinical studies, the most common side effects of Advantan® cream were burning and itching at the application site.
The frequency of adverse reactions observed in clinical studies and listed in the table below is defined according to MedDRA (version 12.0): very common (> 1/10); common (> 1/100, < 1/10); uncommon (> 1/1000, < 1/100); rare (< 1/10000); not known (frequency cannot be estimated from the available data).
| Organs and systems | Frequent | Infrequent | Single |
| Infections and infestations | | Fungal skin infections | |
| General disorders and administration site conditions | Burning and itching at the application site | Dryness, erythema, vesicles, folliculitis, rash, application site paresthesia | Cellulite, swelling, irritation |
| Skin and subcutaneous tissue disorders | | | Pyoderma, skin fissures, telangiectasias, skin atrophy, acne |
| Immune system disorders | | Hypersensitivity to the drug | |
Also, when using Advantan® cream, in rare cases, adverse reactions such as bacterial cellulitis and skin infections may occur.
As with other topical corticosteroids, side effects (frequency not known) may occur, such as thinning of the skin (skin atrophy), the appearance of striae, inflammation of the hair follicles (folliculitis) at the site of application, excessive hair growth (hypertrichosis), telangiectasia, perioral dermatitis, skin discoloration, contact dermatitis and allergic skin reactions to any of the components of the drug.
In some cases, systemic effects of corticosteroids may occur due to their absorption.
The preparation contains cetostearyl alcohol, butylhydroxytoluene, which may cause the development of local reactions such as contact dermatitis; butylhydroxytoluene may cause irritation of the eyes and mucous membranes.
If any adverse reactions occur, discontinue use of the drug and consult a doctor.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Packaging
5 g or 15 g in a tube; 1 tube in a cardboard pack.
Vacation category
Without a prescription.
Producer
LEO Pharma Manufacturing Italy SRL
Location of the manufacturer and address of its place of business.
Via E. Schering, 21, 20054 Segrate (MI), Italy
