Consumer medicine information

Advantan Ointment, Fatty Ointment, Cream & Lotion

Methylprednisolone aceponate

BRAND INFORMATION

Brand name

Advantan

Active ingredient

Methylprednisolone aceponate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Advantan Ointment, Fatty Ointment, Cream & Lotion.

What is in this leaflet?

This leaflet answers some common questions about using the medicine Advantan®. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Advantan® against the benefits it is expected to have for you.

If you have any concerns about using Advantan®, talk to your doctor or pharmacist.

What Advantan® is used for

The active ingredient in Advantan® belongs to the group of medicines called corticosteroids. The corticosteroid in Advantan® is suitable to put on the skin. It is therefore called a topical corticosteroid, which is sometimes shortened to topical steroid.

When Advantan® is put on the skin, it relieves the redness, swelling, itching and irritation of the skin in eczema and psoriasis.

Advantan® preparations are available only with a doctor's prescription.

Advantan® is made up as four different preparations. Each has a distinct look and feel. They are:

  • ointment
  • fatty ointment
  • cream and
  • lotion

The most solid is the fatty ointment; the most runny is the lotion. The ointment and cream are in-between in thickness.

Each preparation is especially suitable in consistency for a particular area of skin or skin condition needing treatment. Your doctor will prescribe the preparation most suitable for you.

The Advantan® preparations are medicines and should only be used on skin affected by the conditions described below.

All four Advantan® preparations treat eczema.

Advantan® ointment, fatty ointment and cream (but NOT lotion) also treat psoriasis.

Eczema is a skin condition with redness, swelling, oozing of fluid, crusting and later scaling. It is often very itchy.

Psoriasis is a skin disorder with raised, rough, reddened areas covered with dry, fine, silvery scales.

Your doctor may have prescribed Advantan® for another reason.

Discuss this with him/her.

Advantan® is not addictive. It is not expected to affect your ability to drive a car or operate machinery.

Before you use Advantan®

When you must not use Advantan®

Do not use Advantan® if you have an allergy to:

  • any medicine containing methylprednisolone aceponate
  • any of the ingredients listed at the end of this leaflet (see Product description).
  • any other similar medicine, that is, topical corticosteroids.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not use Advantan® if in the area of skin you are treating:

  • you have infection due to
    - tuberculosis (TB) or syphilis
    - a virus such as chicken-pox or shingles
    - a skin reaction following a vaccination.

Do not use Advantan® if you have acne, rosacea, ulcers, atrophic skin disease or perioral dermatitis. Your doctor will identify these conditions for you.

Do not use Advantan®

  • after the expiry date printed on the pack OR
  • if the packaging is torn, doesn't look quite right or shows signs of tampering.

If the Advantan® packaging is damaged or it is past the expiry date, return it to your pharmacist for disposal.

If you have not told your doctor about any of the above, tell him/her before you start using Advantan®.

If you are not sure whether you should start using this medicine, talk to your doctor.

Before you start to use it

Tell your doctor if you have a known allergy to Advantan® or any ingredients listed at the end of this leaflet.

Tell your doctor if you

  • are pregnant or plan to become pregnant
  • are breast-feeding
  • plan to breastfeed.

Your doctor can discuss with you the risks and benefits of using Advantan®.

Advantan® should be used only on the skin. Avoid getting Advantan® in your eyes. Do not put Advantan® in your mouth or come in contact with deep open wounds or mucous membranes.

Do not swallow Advantan®.

Taking other medicines

Tell your doctor or pharmacist if you are on any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using Advantan®.

How to use Advantan®

Follow carefully all directions given to you by your doctor or pharmacist. They may differ from the information contained in this leaflet.

If you do not understand the instructions in this leaflet, ask your doctor or pharmacist for help.

How to use Advantan® preparations

  • Advantan® ointment, fatty ointment and cream
    Apply thinly to the affected area of skin.
  • Advantan® lotion
    Apply thinly to the affected area of skin and gently rub in.

When to use it

  • Treatment of eczema
    Use Advantan® once a day to treat the affected skin.
  • Treatment of psoriasis
    Use Advantan® ointment, fatty ointment or cream once or twice a day on the patches of psoriasis.

How long to use it

Usually, treatment with Advantan® is for up to 12 (twelve) weeks in adults and 4 (four) weeks in children.

Treatment with Advantan® should be for the shortest possible time period, and minimised to only on affected area. This is particulary important when using Advantan® under bandages.

This is particularly important when treating large areas, and in children.

Excessive application of topical corticosteroids to large areas of the body for prolonged periods of time can increase the risk of side effects. Discuss this with your doctor.

If you forget to use it

If you forget to use Advantan®, use it as soon as you remember. Then go on as before.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your doctor or pharmacist for some hints.

If you use too much or use it other than directed (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia or 0800 764 766 in New Zealand) for advice, or go to the Emergency Department at the nearest hospital, if you think that you or anyone else may have used too much or swallowed some of this medicine. Do this even if there are no signs of discomfort or poisoning.

If you use too much Advantan® or use it for a long time, you may notice the following in the treated area:

  • your skin becomes thinner
  • pink/purple stretch marks appear
  • a network of tiny blood vessels appears.

Stop using Advantan® if you have these symptoms and tell your doctor.

These symptoms usually disappear about two weeks after you stop using Advantan®.

While you are using Advantan®

Things you must do

Stop using Advantan® if you develop a skin allergy.

Tell your doctor if your skin becomes very dry when you use Advantan® cream or lotion. Your doctor may prescribe Advantan® ointment or fatty ointment instead.

If your eczema or psoriasis is infected, you must

  • use specific anti-infection treatments prescribed by your doctor
  • Stop using Advantan® if the infection spreads.

If you are going to start any new medicine, tell your doctor and pharmacist that you are using Advantan®.

If you become pregnant while using Advantan®, tell your doctor immediately.

Things you must not do

Do not use Advantan® to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

See also the section with the heading Before you use Advantan®.

Side effects

As with all medicines, Advantan® can cause some side effects. Side effects not listed in this leaflet may occur in some patients.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist:

  • if you have any unpleasant effects while you are using Advantan®
    or
  • if you notice any of the following and they worry you:
    - itching
    - burning
    - redness

The above list includes the more common side effects.

The following list includes side effects that are rare:

  • thinning of the skin
  • the appearance of fine blood vessels on the skin surface
  • stretch marks
  • acne
  • infection of hair follicles
  • excessive unwanted hair growth
  • redness and irritation around the mouth (perioral dermatitis)
  • skin discolouration
  • allergic skin reactions.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Advantan®

Keep Advantan® in its pack until required.

Storage

Keep your Advantan® ointment or cream in a cool dry place where the temperature stays below 25°C.

Keep your Advantan® fatty ointment or lotion in a cool dry place where the temperature stays below 30°C.

Do not store Advantan® or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep Advantan® where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Do not use Advantan® after the expiry date on the pack.

Disposal

If your doctor tells you to stop using Advantan® or the expiry date has passed, ask your pharmacist what to do with any Advantan® that is left over.

Product description

What Advantan® formulations looks like

Advantan® ointment is a white to yellowish, opaque ointment, with a firm consistency.

Advantan® fatty ointment is a white to yellowish, semi-clear ointment, which is greasier than Advantan® ointment.

Advantan® cream is a white cream, lighter in consistency than the ointments, and less greasy.

Advantan® lotion is a white lotion, more fluid than the cream.

In New Zealand only Advantan® ointment and Advantan® cream are available.

Ingredients

Advantan® ointment contains 1 mg of methylprednisolone aceponate per gram of ointment as the active ingredient. It also contains

  • white beeswax
  • heavy liquid paraffin
  • white soft paraffin
  • Dehymuls E
  • purified water

Advantan® fatty ointment contains 1 mg of methylprednisolone aceponate per gram of fatty ointment as the active ingredient. It also contains

  • heavy liquid paraffin
  • white soft paraffin
  • microcrystalline wax
  • hydrogenated castor oil.

Advantan® cream contains 1 mg of methylprednisolone aceponate per gram of cream as the active ingredient. It also contains

  • decyl oleate
  • glyceryl monostearate
  • cetostearyl alcohol
  • hard fat
  • Softisan 378
  • PEG-40 stearate
  • glyceryl 85%
  • butylated hydroxytoluene
  • benzyl alcohol
  • disodium edetate
  • purified water

Advantan® lotion contains 1 mg of methylprednisolone aceponate per gram of lotion as the active ingredient. It also contains

  • medium chain trigylcerides
  • caprylic/capric/stearic triglycerides
  • steareth-2
  • steareth-21
  • benzyl alcohol
  • disodium edetate
  • glycerol
  • purified water

Advantan® does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

The Australian Registration Numbers are

Advantan® ointment AUST R 49381

Advantan® fatty ointment: AUST R 49382

Advantan® cream: AUST R 49380

Advantan® lotion: AUST R 80272

This is not all the information available on Advantan®. If you have any more questions or are unsure about anything, ask your doctor or pharmacist.

Sponsor

Advantan® is sponsored in Australia by:

LEO Pharma Pty Ltd
Brisbane, QLD
Australia

Australia Toll Free No. 1800 991 778
New Zealand Toll Free No. 0800 497 456

This leaflet was prepared in July 2019

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Advantan

Active ingredient

Methylprednisolone aceponate

Schedule

S4

 

1 Name of Medicine

Methylprednisolone aceponate.

6.7 Physicochemical Properties

The chemical name is 21-acetoxy-11β-hydroxy -6α-methyl- 17-propionyloxy-1, 4-pregnadiene-3, 20-dione. The molecular formula is C27H36O7. The molecular weight is 472.58.
The active ingredient of the Advantan formulations is the synthetic corticosteroid methylprednisolone aceponate (MPA), which is a white crystalline powder. Methylprednisolone aceponate is soluble in methylene chloride, acetone and ethyl acetate and is sparingly soluble in hexane and ether.

Chemical structure.

The chemical structure is:

CAS number.

86401-95-8.

2 Qualitative and Quantitative Composition

Advantan cream, lotion, ointment or fatty ointment contains methylprednisolone aceponate 1 mg/g (0.1%).
List of excipients with known effect: Advantan cream contains cetostearyl alcohol and butylated hydroxytoluene.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Advantan lotion is an oil-in-water emulsion containing 68% purified water.
Advantan cream is an oil-in-water emulsion containing about 60% purified water.
Advantan ointment is a water-in-oil emulsion containing 30% purified water.
Advantan fatty ointment is a monophasic ointment with 96.9% hydrocarbons.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

After topical application, Advantan (methylprednisolone aceponate) has anti-inflammatory, anti-pruritic and vasoconstrictive actions.
As for all other glucocorticoids, the mechanism of action of methylprednisolone aceponate is not completely understood. It is known that methylprednisolone aceponate binds to the intracellular glucocorticoid receptor as does the principal metabolite 6α-methylprednisolone-17-propionate, which is formed by cleavage in the skin. The steroid-receptor complex binds to certain regions of DNA, inducing anti-inflammatory, anti-pruritic and vasoconstrictive effects.
Binding of methylprednisolone aceponate or its metabolites to the steroid receptor results in the induction of lipomodulin synthesis. Lipomodulin, a protein secondary messenger (also known as lipocortin 1 and macrocortin) inhibits release of arachidonic acid, which in turn inhibits the formation of inflammatory mediators, such as prostaglandins and leukotrienes.
The immunosuppressive action of glucocorticoids can be explained in part by their inhibitory effects on chemotaxis (inhibition of leukotriene synthesis). Glucocorticoids also have anti-mitotic activity, which is not well understood.
The vasoconstrictive activity of glucocorticoids results from the inhibition of prostaglandin synthesis. Prostaglandins have vasodilatory actions. Glucocorticoids also potentiate the vasoconstrictive effect of adrenaline.
Please note that the base formulations of the various Advantan presentations influence the therapeutic effects (see Section 4.2 Dose and Method of Administration).

Clinical trials.

Topical treatment of eczema in adults using methylprednisolone aceponate 1 mg/g lotion.

The effectiveness of Advantan lotion and other topical corticosteroids was measured by standardised clinical assessment of signs and symptoms from which a total (sum) score for comparison was derived. The observed difference (up to 20%) in comparative sum scores is considered within norms for observer variability, and not clinically meaningful. In clinical studies, where active treatment arms were compared, the ratio of effectiveness of the two treatments did not vary by more than 20%. The statistically significant equivalence band for 95% CI of ratios was 0.8-1.25.
One double-blind, multicentre, randomised, vehicle-controlled study assessed the efficacy and safety of methylprednisolone aceponate (MPA) lotion 1 mg/g applied topically twice daily in patients with eczema. The study was 14 days duration. The primary efficacy endpoint was the total score of selected objective and subjective symptoms of eczema (erythema, oedema, vesicles, papules, weeping and itching). The mean total score at the end of treatment was statistically significant (p=0.001, one-sided) favouring MPA. See Table 4.
One double-blind, multicentre, randomised, vehicle-controlled study of 14 days duration assessed the efficacy and safety of MPA lotion 1 mg/g applied twice daily versus amcinonide 0.1% lotion twice daily in patients with eczema. The primary efficacy endpoint was the total score of selected objective and subjective symptoms of eczema (erythema, oedema, vesicles, papules, weeping and itching). The mean total score at the end of treatment was statistically significant (p=0.036, one-sided) favouring MPA over placebo; MPA lotion was equivalent to amcinonide lotion (95% CI: 0.94, 1.11). See Table 5.
One double-blind, multicentre, randomised study of 14 days duration assessed the efficacy and safety of MPA lotion 1 mg/g vs betamethasone 17-valerate 0.1% lotion in patients with eczema. MPA lotion was applied either once or twice daily, whereas betamethasone was applied twice daily. The primary efficacy endpoint was total score of selected objective and subjective symptoms of eczema (erythema, oedema, vesicles, papules, weeping and itching). At the end of treatment, MPA lotion was equivalent to betamethasone lotion. See Table 6.
One double-blind, multicentre, randomised study assessed the efficacy and safety of MPA lotion 1 mg/g versus amcinonide 0.1% lotion in patients with eczema. MPA lotion was applied either once or twice daily, whereas amcinonide was applied twice daily. The study was of 14 days duration. The primary efficacy endpoint was the total score of selected objective and subjective symptoms of eczema (erythema, oedema, vesicles, papules, weeping and itching). At the end of treatment, MPA lotion was equivalent to amcinonide lotion. See Table 7.

Topical treatment of eczema in children using methylprednisolone aceponate 1 mg/g lotion.

One double-blind, multicentre, randomised study assessed the efficacy and safety of MPA lotion 1 mg/g versus hydrocortisone 17-butyrate 0.1% lotion in paediatric patients with eczema. MPA lotion was applied once daily, and hydrocortisone 17-butyrate was applied twice daily. The study was of 14 days duration. The primary efficacy endpoint was the total score of selected objective and subjective symptoms of eczema (erythema, oedema, vesicles, papules, weeping and itching).
At the end of treatment MPA lotion was equivalent to hydrocortisone 17-butyrate lotion (MPA vs hydrocortisone 17-butyrate: 95% CI: 0.88, 1.09). See Table 8.

5.2 Pharmacokinetic Properties

Absorption.

Methylprednisolone aceponate is bioavailable from all formulations (cream, ointment, fatty ointment and lotion). When applied topically the concentration of methylprednisolone aceponate is highest in the outer layer of the epidermis (stratum corneum) and decreases progressively in the deeper strata.
The degree of percutaneous absorption of methylprednisolone aceponate varies according to the state of the skin (intact/inflamed/damaged), the formulation (ointment/fatty ointment/cream/lotion) and the conditions of application (open/occlusion). Studies using the ointment, fatty ointment and cream formulations in juvenile and adult patients with neurodermatitis and psoriasis have shown that the percutaneous absorption on open application was slightly (≤ 2.5%) greater than the percutaneous absorption in volunteers with normal skin (0.2 - 1.5%). Occlusive dressing increased percutaneous absorption. When the superficial horny layer is removed before application of methylprednisolone aceponate, the corticoid levels in the skin are about three times higher than after application to intact skin.
Skin was artificially damaged to investigate the percutaneous absorption of methylprednisolone aceponate from the lotion formulation. Intact skin was compared with both artificially inflamed (UV-B erythema) and artificially damaged (removal of horny layer) skin. The absorption through artificially inflamed skin was very low (0.27%) and was only marginally higher than the absorption through intact skin (0.17%). The percutaneous absorption of methylprednisolone aceponate through artificially damaged skin resulted in higher levels of corticoid in the skin (15%).

Distribution.

The systemic effects of methylprednisolone aceponate are minimal in both man and animals following application of a topically effective dose. After treatment of large areas in 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.

Metabolism.

Methylprednisolone aceponate is hydrolysed in the epidermis and dermis to the principal metabolite, 6α-methylprednisolone- 17-propionate. This metabolite binds to the intracellular glucocorticoid receptor with higher affinity than methylprednisolone aceponate. The binding of 6α-methylprednisolone- 17-propionate to the receptor is an indicator of "bioactivation" in the skin.
After absorption into the systemic circulation, the primary hydrolysis product of methylprednisolone aceponate, 6α-methylprednisolone- 17-propionate, is rapidly conjugated with glucuronic acid, and as a result, inactivated.

Excretion.

The principal metabolites of methylprednisolone aceponate are eliminated primarily via the kidneys. The half-life is about 16 hours. Following intravenous administration, excretion via the urine and faeces was complete within 7 days. There is no accumulation of methylprednisolone aceponate or metabolites in the body.

5.3 Preclinical Safety Data

Genotoxicity.

Methylprednisolone aceponate did not elicit any genotoxic effects or chromosomal damage in in vitro and in vivo assays conducted in bacteria and mammalian cells.

Carcinogenicity.

Animal studies to evaluate the carcinogenic potential of methylprednisolone aceponate have not been conducted. Other glucocorticoid drugs have been shown to cause hepatic tumours in rats, and it must be assumed that methylprednisolone aceponate would have similar activity. However, in humans, epidemiological surveys of many years of systemic glucocorticoid therapy have not revealed any evidence for a tumourigenic action of this substance class.

4 Clinical Particulars

4.1 Therapeutic Indications

Advantan cream, ointment and fatty ointment are indicated for the topical treatment of eczema and psoriasis in adults and children.
Advantan lotion is indicated for the topical treatment of eczema in adults and children.

4.3 Contraindications

Advantan is contraindicated in 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, ulcera, atrophic skin diseases, acne vulgaris or perioral dermatitis are present, Advantan must not be applied to the face.
Hypersensitivity to methylprednisolone aceponate or any component of the formulations.
Children under four months due to lack of experience.

4.4 Special Warnings and Precautions for Use

For external use only.

Advantan should not be allowed to come into contact with deep open wounds, muscosae or the eyes when being applied to the face.
Additional specific therapy is required in skin conditions infected with bacteria and/or fungi. Any spread of infection requires withdrawal of topical corticosteroid therapy.
If the skin dries out excessively under protracted use of Advantan cream or lotion, a change should be made to one of the formulations with a higher fat content (Advantan ointment or fatty ointment).
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.
As known from systemically administered corticosteroids, glaucoma may also develop from using topical corticosteroids (e.g. after large dose or extensive application over a prolonged period, application under occlusive dressings, or application to skin around or near the eyes).
Advantan is a potent steroid formulated for topical application. As with all potent corticosteroids, the possibility of hypothalamic-pituitary-adrenal (HPA) axis suppression resulting from percutaneous absorption of methylprednisolone must be considered when initiating or reviewing therapy, as adequate studies are not available to define the degree of risk.
Treatment of large areas has been noted to produce some suppression of cortisol secretion, but plasma levels remain above the lower limit of the normal range and circadian rhythm is maintained. Nevertheless, when treating large areas the 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 side effects. This is particularly important in children who may absorb proportionately larger amounts of topical corticosteroid and thus be more susceptible to systemic toxicity.
Systemic absorption of topical corticosteroids will be increased if extensive body surface areas are treated or if the occlusive technique is used. Suitable precautions should be taken under these conditions or when long-term use is anticipated.
Local atrophy, telangiectasia and striae may occur after prolonged treatment or excessive application. Treatment should be discontinued if symptoms such as cutaneous atrophy occur (also see Section 4.8 Adverse Effects (Undesirable Effects)).
There was no sensitising effect or potential in animal studies.
Some of the excipients in Advantan cream, lotion, ointment and fatty ointment may reduce the effectiveness of latex products such as condoms and diaphragms.
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.

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.

Use in the elderly.

No data available.

Paediatric use.

In infants and children, plastic pants and napkins may act as occlusive dressings and increase absorption. Because of children's larger skin surface area to bodyweight ratio, paediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than adults. Chronic/long-term corticosteroid therapy may interfere with growth and development of children. Use of topical corticosteroids in children should be limited to the least amount required for therapeutic effect.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No specific information exists on interactions with other medications.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
There are no adequate data from the use of Advantan cream, ointment and fatty ointment in pregnant women.
Animal studies with methylprednisolone aceponate have shown embryolethal effects in rats dosed subcutaneously during the period of organogenesis at doses greater than 1 mg/kg/day and in rabbits following dermal application at doses greater than 0.25 mg/kg/day. No teratogenic effects were observed in rabbits, but in rats the incidence of ventricular septal defects and of cleft palate were increased at subcutaneous doses greater than 1 and 10 mg/kg/day. Epidemiological studies suggest that there could possibly be an increased risk of oral clefts among newborns or women who were treated with glucocorticosteroids during the first trimester of pregnancy. In general, the use of topical preparations containing corticoids should be avoided during the first trimester of pregnancy.
Reduced placental and birth weight have been recorded in animals and humans after long-term treatment. 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.
The clinical indication for treatment with methylprednisolone aceponate must be carefully reviewed and the benefits weighed against the risks in pregnant and lactating women. Treatment of large areas or prolonged use (greater than 4 weeks) must be avoided.
It is not known whether methylprednisolone aceponate is secreted in breast milk. Methylprednisolone aceponate should be used during lactation only if benefits outweigh the risks.
Nursing mothers should avoid treatment over large areas, prolonged use or occlusive dressings. Advantan should not be applied to the chest area during breast feeding to avoid possible ingestion by infants.
When considering use during lactation, note that after systemic administration, very small amounts of glucocorticoid may be present in breast milk. There is only a slight risk of exposure to methylprednisolone aceponate in breast milk following maternal dermal application at therapeutic doses, because the systemic absorption of methylprednisolone aceponate is minimal.

4.8 Adverse Effects (Undesirable Effects)

In clinical studies, most frequently observed side-effects included application site burning and application site pruritus with Advantan cream and ointment. For Advantan fatty ointment, application site folliculitis and application site burning were observed most frequently.
Frequencies of side-effects observed in clinical studies and given in Tables 1, 2 and 3 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.
As with other corticoids for topical application, the following local side effects may occur: skin atrophy, skin striae, application folliculitis, hypertrichosis, telangiectasia, perioral dermatitis, skin discolouration, and hypersensitivity to any of the ingredients of the formulations. Systemic effects due to absorption may occur when topical preparations containing corticoids are applied.

Post marketing.

Eye disorders: vision blurred.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Advantan is for external topical use only and not for ophthalmic use.
The Advantan formulation most appropriate to the skin condition should be used.
If the skin dries out excessively during treatment with Advantan cream or lotion, a change should be made to one of the formulations with a higher fat content i.e. Advantan ointment or fatty ointment.
The duration of use should be less than 12 weeks in adults and less than 4 weeks in children.

Instructions for use.

Do not use beyond the expiry date on the package.
Do not use if the pack shows signs of damage or tampering.

Advantan ointment, fatty ointment and cream.

Advantan ointment, fatty ointment or cream should usually be applied as a thin coating once per day to the affected areas. In the treatment of psoriasis, twice daily application may be required.

Advantan lotion.

Advantan lotion should be applied sparingly once daily to the affected areas and rubbed in gently.

Choice of formulation.

Advantan lotion.

Advantan lotion's formulation confers cooling properties. It is intended primarily for the treatment of acute eczema, where acute inflammation and tenderness is present. Because it is the least occlusive of the Advantan formulations, it is suitable for treatment of large areas and skin flexures, as well as hirsute regions.

Advantan cream.

As a low-fat formulation with a high water content, Advantan cream is suitable for acute and subacute weeping stages of eczema, for very greasy skin and for use on exposed or hirsute areas.

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 the axilla, groin or skin folds. Advantan ointment makes the skin slightly greasy without retaining warmth and fluid.

Advantan fatty ointment.

Very dry skin and the chronic stage of skin conditions require an anhydrous base. Advantan fatty ointment base has an occlusive effect. It is suitable for treatment of areas where the stratum corneum is particularly thick, such as the pressure areas of elbows, knees, palms and soles.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Excessive dosing may occur with prolonged or intensive topical use. See Section 4.8 Adverse Effects (Undesirable Effects) for further information.
Acute toxicity studies with methylprednisolone aceponate (namely oral ingestion, or single dermal application to a large area, under conditions favourable to absorption) do not indicate that any acute intoxication is expected.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Advantan lotion.

Medium chain triglycerides, caprylic/capric/stearic triglycerides, steareth-2, steareth-21, benzyl alcohol, disodium edetate, glycerol and purified water.

Advantan cream.

Decyloleate, glyceryl monostearate, cetostearyl alcohol, hard fat, Softisan 378, PEG-40 stearate, glyceryl 85%, butylated hydroxytoluene, benzyl alcohol, disodium edetate and purified water.

Advantan ointment.

White soft paraffin, heavy liquid paraffin, white beeswax, Dehymuls E and purified water.

Advantan fatty ointment.

Contains the excipients: white soft paraffin, heavy liquid paraffin, microcrystalline wax and hydrogenated castor oil.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Advantan ointment or cream.

Store below 25°C.

Advantan fatty ointment or lotion.

Store below 30°C.

6.5 Nature and Contents of Container

Advantan lotion is available in tubes of 20 g or 50 g.
Advantan cream is available in tubes of 5 g, 10 g, 15 g, 30 g, 50 g or 100 g.
Advantan ointment is available in tubes of 5 g, 10 g, 15 g, 30 g, 50 g or 100 g.
Advantan fatty ointment is available in tubes of 5 g, 10 g, 15 g, 30 g, 50 g or 100 g.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes