Advantan

Main information

  • Trade name:
  • Advantan 0.1 % Topical ointment
  • Dosage:
  • 0.1 %
  • Pharmaceutical form:
  • Topical ointment
  • Units in package:
  • Tube, aluminium, epoxide coating, screw cap, 15 g
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Bayer AG

Documents

Localization

  • Available in:
  • Advantan 0.1 % Topical ointment
    New Zealand
  • Language:
  • English

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 6262
  • Authorization date:
  • 05-11-1997
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

ADVANTAN

Data Sheet

Page 1 of 9

ADVANTAN

®

Methylprednisolone aceponate 0.1% ointment/cream

Presentation

1 g cream or ointment contains 1 mg (0.1%) methylprednisolone aceponate.

Uses

Actions

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

-methyl -

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

leukotrienes.

The immunosuppressive action of glucocorticoids can be explained by

inhibition of cytokine synthesis and an antimitotic effect, which so far is not

well understood.

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

ADVANTAN

formulations.

ADVANTAN

Data Sheet

Page 2 of 9

ADVANTAN

cream

As a low-fat formulation with a high water content, ADVANTAN

cream is

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.

ADVANTAN

ointment

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

formulations, ADVANTAN

ointment has the widest field of use.

Pharmacokinetics

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

MPA, 6

methylprednisolone-17-propionate, is quickly conjugated with

glucuronic acid and inactivated as a result.

The metabolites of MPA (main metabolite: 6

-methylprednisolone-17-

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.

Indications

Atopic dermatitis (endogenous eczema, neurodermatitis), contact eczema,

degenerative, dyshidrotic, vulgar eczema, eczema in children.

ADVANTAN

Data Sheet

Page 3 of 9

Dosage and Administration

ADVANTAN

is for EXTERNAL TOPICAL USE ONLY and NOT FOR

OPTHALMIC USE.

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.

Contraindications

ADVANTAN

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

cream,

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.

ADVANTAN

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

ADVANTAN

for up to 12 weeks in adults or 4 weeks in children.

ADVANTAN

Data Sheet

Page 4 of 9

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.

ADVANTAN

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

ADVANTAN

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

membranes.

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

ADVANTAN

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

of ADVANTAN

under the recommended conditions of use, no influence on

the occurrence of tumors is to be expected.

ADVANTAN

Data Sheet

Page 5 of 9

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

of MPA.

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

during pregnancy.

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

overload.

As a general rule, topical preparations containing corticoids should not be

applied during the first trimester of pregnancy. The clinical indication for

ADVANTAN

Data Sheet

Page 6 of 9

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

avoided.

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

woman.

Nursing mothers should not be treated on the breasts. Treating large areas,

prolonged use or occlusive dressings should be avoided during lactation.

Adverse Effects

In clinical studies, most frequently observed side-effects included application

site burning and application site pruritus with ADVANTAN

cream and

ointment.

Frequencies of side-effects observed in clinical studies and given in the table

below are

defined according to the MedDRA frequency convention: very

common (>1/10);

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

common

uncommon

rare

General disorders and

administration site

reaction

application site

burning, application

site pruritus

application site

dryness, application

site erythema,

application site

vesicles, application

site folliculitis,

application site

rash, application

site paraesthesia

application site

cellulitis, application

site oedema,

application site

irritation

Immune system

disorders

drug

hypersensitivity

Skin and subcutaneous

tissue disorders

pyoderma, skin

fissures,

telangiectasia, skin

atrophy, fungal skin

infection, acne

ADVANTAN

Data Sheet

Page 7 of 9

Advantan Ointment 0.1%

System organ class

common

uncommon

not known

(cannot be

estimated from

available data)

General disorders

and administration

site reaction

application site

burning, application

site pruritus

application site

erythema, application

site dryness,

application site

vesicles, application

site irritation,

application site

eczema, application

site papules, oedema

peripheral

Skin and

subcutaneous tissue

disorders

skin atrophy,

ecchymosis, impetigo,

skin greasy

acne

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

applied.

Interactions

None so far known.

Overdosage

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.

Pharmaceutical Precautions

ADVANTAN

®

cream/ointment

ADVANTAN

Data Sheet

Page 8 of 9

Shelf life: 3 years

Special precautions for storage: Store below 25

Medicine Classification

Prescription Medicine

Package Quantities

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.

Further Information

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),

purified water

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

polyethylene.

Instructions for use/handling

Store all drugs properly and keep them out of reach of children.

ADVANTAN

Data Sheet

Page 9 of 9

Name and Address

Sponsor

Seqirus (NZ) Ltd

PO Box 62 590

Greenlane

Auckland 1546

NEW ZEALAND

Telephone: 09 579 8105

Date of Preparation

02 February 2017

29-8-2018

Cortacare (Ecuphar NV)

Cortacare (Ecuphar NV)

Cortacare (Active substance: Hydrocortisone aceponate) - Centralised - Authorisation - Commission Decision (2018)5781 of Wed, 29 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/V/C/4689

Europe -DG Health and Food Safety