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Methylprednisolone aceponate 0.1% ointment/cream
1 g cream or ointment contains 1 mg (0.1%) methylprednisolone aceponate.
After topical application, ADVANTAN
suppresses inflammatory and allergic
skin reactions as well as reactions associated with hyperproliferation, leading
to regression of the objective symptoms (erythema, edema, infiltration,
lichenification) and the subjective complaints (itching, burning, pain).
On application of methylprednisolone aceponate in topically effective dosage,
the systemic effect is minimal in both man and animals. After large-area
treatment of patients with skin disorders, the plasma cortisol values remain
within the normal range, circadian cortisol rhythm is maintained and no
reduction of cortisol has been ascertained in 24-hour urine.
As for all other glucocorticoids, so far the mechanism of action of
methylprednisolone aceponate is not completely understood. It is known that
methylprednisolone aceponate itself binds to the intracellular glucocorticoid
receptor and this is especially true of the principal metabolite 6
prednisolone -17-propionate, which is formed after cleavage in the skin.
The steroid receptor complex binds to certain regions of DNA, thereby
triggering a series of biological effects.
The understanding of the mechanism of the anti-inflammatory action is more
precise. Binding of the steroid receptor complex results in induction of
macrocortin synthesis. Macrocortin inhibits the release of arachidonic acid
and thus the formation of inflammation mediators such as prostaglandins and
The immunosuppressive action of glucocorticoids can be explained by
inhibition of cytokine synthesis and an antimitotic effect, which so far is not
Inhibition of the synthesis of vasodilating prostaglandins or potentiation of the
vasoconstrictive effect of epinephrine finally results in the vasoconstrictive
activity of glucocorticoids.
The respective bases are of major importance to the therapeutic effect of the
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As a low-fat formulation with a high water content, ADVANTAN
particularly suitable for acute and subacute weeping stages of eczema, for
very greasy skin and for use on exposed or hairy parts of the body.
Skin conditions which are neither weeping nor very dry require a base with
balanced proportions of fat and water. ADVANTAN
ointment is suitable for
dry, fissured, scaly or hyperkeratinised skin areas. It should not be used in
areas such as axilla, groin or skin folds. ADVANTAN
ointment makes the
skin slightly greasy without retaining warmth and fluid. Of the three
ointment has the widest field of use.
Methylprednisolone aceponate (MPA) becomes available in the skin from all
formulations (cream, ointment). The concentration in the stratum corneum
and living skin decreases from outside to inside.
Methylprednisolone aceponate is hydrolyzed in the epidermis and dermis to
the main metabolite 6
-methylprednisolone-17-propionate which binds more
firmly to the corticoid receptor – an indication of “bioactivation” in the skin.
The degree of percutaneous absorption depends on the state of the skin, the
formulation and the conditions of application (open/occlusion). Studies in
juvenile and adult patients with neurodermatitis and psoriasis have shown
that the percutaneous absorption on open application was only slightly
2.5%) greater than the percutaneous absorption in volunteers with normal
skin (0.5 - 1.5 %).
When the horny layer is removed before the application, the corticoid levels in
the skin are about three times higher than after application to intact skin.
After reaching the systemic circulation, the primary hydrolysis product of
methylprednisolone-17-propionate, is quickly conjugated with
glucuronic acid and inactivated as a result.
The metabolites of MPA (main metabolite: 6
propionate-21- glucuronide) are eliminated primarily via the kidneys with a
half-life of about 16 hours. Following i.v. administration, excretion of the
labeled substances with the urine and feces was complete within 7 days. No
accumulation of substance or metabolites takes place in the body.
Atopic dermatitis (endogenous eczema, neurodermatitis), contact eczema,
degenerative, dyshidrotic, vulgar eczema, eczema in children.
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Dosage and Administration
is for EXTERNAL TOPICAL USE ONLY and NOT FOR
In general, the ADVANTAN
formulation appropriate to the skin condition is
applied thinly once per day to the diseased areas of skin.
In general, the duration of use should not exceed 12 weeks in adults and 4
weeks in children.
is contraindicated in most viral diseases (e.g. vaccinia,
varicella/herpes zoster) and when tuberculous or syphilitic processes and
post-vaccination skin reactions are present in the area to be treated. If
rosacea, acne vulgaris, ulcera, atrophic skin diseases, or perioral dermatitis
are present, ADVANTAN
must not be applied to the face.
Hypersensitivity to the active substance or to any of its excipients.
Warnings and Precautions
Care must be taken when using ADVANTAN
to avoid contact with the eyes,
deep open wounds and mucosae.
Additional specific therapy is required in bacterially infected skin diseases
and/or in fungal infections. Any spread of infection may require withdrawal of
topical corticosteroid therapy.
If the skin dries out excessively under protracted use of ADVANTAN
a switch should be made to ADVANTAN
ointment, a formulation which has a
higher fat content.
If signs of hypersensitivity develop ADVANTAN
should be discontinued and
appropriate treatment instituted.
Any of the side effects that have been reported following systemic use of
corticosteroids, including adrenal suppression, may also occur with topical
corticosteroids, especially in infants and children.
is a potent steroid formulation, as with other corticosteroids of
this type the possibility of hypothalmic-pituitary-adrenal (HPA) axis
suppression resulting from percutaneous absorption of methylprednisolone
must be considered when initiating or reviewing therapy. However, to date, no
impairment of adrenocortical function has been observed when used on large
areas (40 - 60 % of the skin surface) or even occlusive treatment with
for up to 12 weeks in adults or 4 weeks in children.
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Nevertheless, for the treatment of large areas duration of use should be kept
as brief as possible.
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 systemic effects. Note that nappies can occlusive.
Paediatric patients may demonstrate greater susceptibility to topical
corticosteroid- induced HPA axis suppression and Cushing’s syndrome than
adults because of a larger skin surface area to bodyweight ratio. Use of
topical corticosteriods in children should be limited to the least amount
required for therapeutic effect. Chronic corticosteroid therapy may interfere
with the growth and development of children.
Local atrophy, telangiectasia and striae may occur after prolonged treatment
or excessive application. Treatment should be discontinued if symptoms such
as cutaneous atrophy occur. Prolonged use on flexures and in intertriginous
areas is undesirable.
cream or ointment should not be used around the eyes. The
use of topical corticosteroids on the face can exacerbate rosacea and lead to
peri-orofacial dermatitis. Patients should be warned against using
on the face except on medical advice and any use on the face
should be restricted to short periods.
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).
Two excipients contained in ADVANTAN
cream (cetostearyl alcohol and
butyl hydroxytoluene) may cause local skin reactions (e.g. contact dermatitis).
Butyl hydroxytoluene may also cause irritation in the eyes and mucous
Preclinical safety data
In systemic tolerance studies following repeated subcutaneous and dermal
administration MPA showed the action profile of a typical glucocorticoid. It can
be concluded from these results that following therapeutic use of
no side-effects other than those typical of glucocorticoids are to
be expected even under extreme conditions such as application over a large
surface area and/or occlusion.
Specific tumorigenicity studies using MPA have not been carried out.
Knowledge concerning the structure, the pharmacological effect mechanism
and the results from systemic tolerance studies with long-term administration
do not indicate any increase in the risk of tumor occurrence. As systemically
effective immunosuppressive exposure is not reached with dermal application
under the recommended conditions of use, no influence on
the occurrence of tumors is to be expected.
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Neither in vitro investigations for detection of gene mutations on bacteria and
mammalian cells nor in vitro and in vivo investigations for detection of
chromosome and gene mutations gave any indication of a genotoxic potential
Animal studies with MPA have shown embryolethal defects in rats dosed
subcutaneously during the period of organogenesis at doses greater than
1mg/kg/day and in rabbits following dermal application at doses greater than
0.25mg/kg/day. No teratogenic effects were observed in rabbits, but in rats
the incidences of ventricular septal defects and of cleft palate were increased
at subcutaneous doses greater than 1 and 10 mg/kg/day. Similar
embryolethal and teratogenic effects have been found with other
corticosteroids and while not considered relevant to humans, particular care
should be taken when prescribing ADVANTAN
In investigations into the local tolerance of MPA and ADVANTAN
formulations on the skin and the mucosa, no findings other than the topical
side-effects known for glucocorticoids were recorded. MPA showed no
sensitizing potential on the skin of the guinea-pig.
Effects on the ability to drive and use machines
There is no effect.
Pregnancy and lactation
Use in Pregnancy
There is no adequate data from the use of ADVANTAN
in pregnant women.
Animal experimental studies with methylprednisolone aceponate have shown
embryonic and/or teratogenic effects (refer to the Warnings and
Precautions section). 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 of occlusive dressing should be
avoided during pregnancy.
Epidemiological studies suggest that there could possibly be an increased
risk or oral clefts among newborns of women who were treated with
glucocorticosteroids during the first trimester of pregnancy.
Reduced placental and birth weight have been recorded in animals and
humans after long-term treatment with topical corticosteroids. Since the
possibility of suppression of the adrenal cortex in the newborn baby after
long-term treatment must be considered, the needs of the mother must be
carefully weighed against the risk to the foetus when prescribing these drugs.
Maternal pulmonary oedema has been reported, with tocolysis and fluid
As a general rule, topical preparations containing corticoids should not be
applied during the first trimester of pregnancy. The clinical indication for
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treatment with ADVANTAN
must be carefully reviewed and the benefits
weighed against the risks in pregnant and lactating women. In particular,
treatment of large areas or prolonged use (greater than 4 weeks) must be
Use in Lactation
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
could result in sufficient systemic absorption of methylprednisolone
aceponate to produce detectable quantities in human milk. Therefore caution
should be exercised when ADVANTAN
are administered to a nursing
Nursing mothers should not be treated on the breasts. Treating large areas,
prolonged use or occlusive dressings should be avoided during lactation.
In clinical studies, most frequently observed side-effects included application
site burning and application site pruritus with ADVANTAN
Frequencies of side-effects observed in clinical studies and given in the table
defined according to the MedDRA frequency convention: very
common (>1/100, <1/10); uncommon (>1/1,000; <1/100),
rare (>1/10,000, <1/1,000);
very rare (<1/10,000), not known (cannot be
estimated from available data). MedDRA
version 12.0 was used for coding.
Advantan Cream 0.1%
System organ class
General disorders and
Skin and subcutaneous
atrophy, fungal skin
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Advantan Ointment 0.1%
System organ class
site papules, oedema
As with other corticoids for topical application, the following local side effects
may occur: skin atrophy, skin striae, application site folliculitis, hypertrichosis,
telangiectasia, perioral dermatitis, skin discolouration, allergic skin reactions
to any of the ingredients of the formulations. Systemic effects due to
absorption may occur when topical preparations containing corticoids are
None so far known.
Symptoms of intoxication
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 favorable to
absorption) or inadvertent oral ingestion.
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Shelf life: 3 years
Special precautions for storage: Store below 25
Tubes containing 15g.
Tubes made of pure aluminum, interior wall coated with epoxy resin, and with
a polyester-based external coating, fold seal ring is made of polyamide-based
heat sealable material. The screw cap is made of high density polyethylene.
List of excipients
Cream: decyl oleate, glycerol monostearate 40 - 55 %, cetostearyl alcohol,
hard fat, caprylic-capric-stearic acid triglyceride (Softisan 378), polyoxyl-40-
stearate, glycerol 85 %, disodium edetatem, benzyl alcohol, butyl
hydroxytoluene, purified water.
Ointment: beeswax (white), paraffin, liquid, Dehymuls E, paraffin (white soft),
Nature and contents of the container
Ointment: Tubes of pure aluminium, interior wall coated with epoxy resin, and
with a polyester-based external coating, fold seal ring is made of polyamide
based heat sealable material. The screw cap is made of high density
Instructions for use/handling
Store all drugs properly and keep them out of reach of children.
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Name and Address
Seqirus (NZ) Ltd
PO Box 62 590
Telephone: 09 579 8105
Date of Preparation
02 February 2017