Advantan Milk Emulsion

Treatment of acute exogenous (allergic contact dermatitis, toxic degenerative eczema, seborrhoeic eczema, nummular (microbial) eczema, dyshidrotic eczema, gravitational eczema, unclassifiable eczema) and endogenous eczema (atopic dermatitis, neurodermatitis).

Posology ADVANTAN u00ae MILK is to be used only as necessary and applied thinly once daily to the affected areas and rubbed in lightly. In general, the duration of use should not exceed 2 weeks. If the skin dries out excessively with the use of the ADVANTAN u00ae MILK a switch should be made to one of the formulations with a higher fat content (ADVANTAN u00ae ointment or fatty ointment). Paediatric population No data are available. S4

Method of administration For external use only.

ADVANTAN u00ae MILK must not be used in cases of hypersensitivity to the active substance or to any of the excipients listed in section 6.1, presence of tuberculous or syphilitic processes, viral infections (such as herpes or varicella), rosacea, perioral dermatitis, ulcers, acne vulgaris, atrophic skin diseases and postvaccination skin reactions in the area to be treated. Bacterial and mycotic skin diseases (see section 4.4). Corticosteroids have been shown to be teratogenic in animals following dermal application. As these agents are absorbed percutaneously, teratogenicity following topical application cannot be excluded. Therefore, ADVANTAN u00ae MILK should not be used during pregnancy (see section 4.6).

Long-term continuous treatment with topical corticosteroids should be avoided as far as possible as this may cause atrophic changes in the skin leading to thinning, loss of elasticity, dilatation of superficial blood vessels, telangiectasiae and ecchymoses. These changes are particularly likely to occur on the face and when occlusive dressings are used. Systemic absorption of topically applied corticosteroids may occur, particularly under the following conditions: when large quantities are used, or when application is made to wide areas of the body, or to damaged skin, when potent topical corticosteroids are used, and when the occlusive dressing technique is applied. Depression of the hypothalamic-pituitary-adrenal axis with consequent suppression of the adrenal gland may occur. These effects are most likely to be severe in children. Growth may be retarded and a Cushingoid state may be produced. Benign increased intracranial pressure has been rarely reported. No impairment of the adrenocortical function has been observed in adults on large area treatment (40 to 60 % of the skin surface) even under occlusive conditions with ADVANTAN u00ae. Nevertheless, the duration of use should be as brief as possible if large areas have to be treated. Additional, specific therapy is required in bacterially infected skin diseases and/or in fungus infections. Local skin infections can be potentiated by topical glucocorticoid use. As with all other glucocorticoids unprofessional use can mask clinical symptomatology. Care must be taken when using ADVANTAN u00ae MILK to avoid contact with the eyes, deep open wounds and mucosae. The clinical indication for treatment with ADVANTAN u00ae MILK must be very carefully reviewed and the benefits weighed against the risks in lactating women. In particular, large area treatment should be avoided (more than 40 % of the body surface). Nursing mothers should not be treated on the breasts (see section 4.6). Topical corticosteroids should be used with particular caution in facial dermatoses, and only for short periods. Steroid rosacea-like facies may be produced. After application of ADVANTAN u00ae 0,1 % Ointment to 60 % skin surface area under occlusive conditions for 22 hours, suppression of plasma cortisol levels and influence on circadian rhythm was observed in adult healthy volunteers. Extensive application of topical corticosteroids to large areas of the body or for prolonged periods of time, in particular under occlusion, significantly increases the risk of side effects. Treatment under occlusive conditions should be avoided unless indicated. Note that diapers as well as intertriginous areas might represent occlusive conditions. As known from systemic corticoids, glaucoma may also develop from using local corticoids (e.g., after large-dosed or extensive application over a prolonged period, occlusive dressing techniques, or application to the skin around the eyes). Visual Disturbance: Visual disturbance may be 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. Regular review should be made of the necessity for continuing therapy. This corticosteroid preparation should not be used in the nappy areas in infants for flexural eruptions, and ideally it should not be applied to infants and young children. The treatment of psoriasis with potent topical corticosteroids may provoke the pustular form of the disease. ADVANTAN u00ae MILK should not be applied to skin crease areas. When treating large areas of skin, the duration of treatment should be kept as short as possible as the possibility of absorption or a systemic effect cannot be completely excluded. Long term continuous or inappropriate 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. Reapplication should be with caution and specialist advise is recommended in these cases or other treatment options should be considered. The excipient (caprylic-capric-myristic-stearic triglyceride) in ADVANTAN u00ae MILK may reduce the effectiveness of latex products such as condoms and diaphragms. This medicine contains 1,25 g benzyl alcohol in each 100 g. Benzyl alcohol may cause allergic reactions and/or mild local irritation.

None so far known. Paediatric population No information available.

Pregnancy There are no adequate data on the use of methylprednisolone aceponate in pregnant women. Animal experimental studies with methylprednisolone aceponate have shown embryotoxic and/or teratogenic effects at doses which exceed the therapeutic dose (see section 5.3). A number of epidemiological studies suggest that there could possibly be an increased risk of oral clefts among newborns of women who were treated with systemic glucocorticoids during the first trimester of pregnancy. In general, the use of topical preparations containing corticoids should be avoided during the first trimester of pregnancy. In particular, treating large areas, prolonged use or occlusive dressings should be avoided during pregnancy and lactation (see section 4.3). Breastfeeding In rats, methylprednisolone aceponate showed practically no transfer to the neonates via the milk. But it is not known if methylprednisolone aceponate is secreted in human milk as systemically administered corticosteroids have been reported to appear in human milk. It is not known whether topical administration of ADVANTAN u00ae MILK could result in sufficient systemic absorption of methylprednisolone aceponate to produce detectable quantities in human milk. Therefore, caution should be exercised when ADVANTAN u00ae MILK is administered to a nursing woman. Nursing mothers should not be treated on the breasts. Treating large areas, prolonged use or occlusive dressings should be avoided during lactation (see section 4.4). Fertility No information about the influence of methylprednisolone aceponate on fertility is available.

ADVANTAN u00ae MILK has no influence on the ability to drive and use machines.

a. Summary of the safety profile Occasionally, ADVANTAN u00ae MILK may lead to local skin irritations such as a mild transient burning sensation. Less frequently, itching, erythema, dry skin, scaling and folliculitis may arise. Hypersensitivity reactions to the components may occur. In clinical studies, the most frequently observed side effect included application site burning. Frequencies of side effects observed in clinical studies and given in the table below are defined according to the MedDRA frequency convention: very common (u22651/10); common ( u22651/100, <1/10); uncommon (u22651/1 000; <1/100), rare (u22651/10 000, <1/1 000); very rare (<1/10 000), not known (cannot be estimated from the available data). The most appropriate MedDRA term was used to describe a certain reaction, its synonyms and related conditions.

b. Tabulated summary of adverse reactions System organ class common uncommon not known Eye disorders Vision blurred (see also section 4.4) * Skin and subcutaneous tissue disorders Eczema, skin exfoliation, skin fissures 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* General disorders and administration site reaction Application site burning Application site pain, application site vesicles, application site pruritus, application site pustules, application site erosion * See also section 4.4.

c. Description of selected adverse reactions As with other corticoids for topical application, the following local side effects may occur (frequency not known): skin atrophy, application site dryness and application site erythema, skin striae, application site folliculitis, hypertrichosis, telangiectasia, perioral dermatitis, skin discoloration, acne, and/or allergic skin reactions to any of the ingredients of the formulation. Systemic effects due to absorption may occur when topical preparations containing corticoids are applied. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Results from acute toxicity studies do not indicate that any risk of acute intoxication is to be expected following a single dermal application of an overdose (application over a large area under conditions favourable to absorption) or inadvertent oral ingestion.