Consumer medicine information

Enstilar

Calcipotriol; Betamethasone

BRAND INFORMATION

Brand name

Enstilar

Active ingredient

Calcipotriol; Betamethasone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Enstilar.

What is in this leaflet?

This leaflet answers some common questions about using the medicine Enstilar®. 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 Enstilar® against the benefits it is expected to have for you.

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

What Enstilar® is used for

Enstilar® is a topical treatment for psoriasis. Psoriasis is a skin disorder in which skin cells are overactive. This causes redness, scaling and thickness of your skin. Enstilar® contains two active ingredients:

  • calcipotriol as monohydrate (related to Vitamin D);
  • betamethasone dipropionate (a corticosteroid).

The calcipotriol in Enstilar® treats the overactive skin cells. The betamethasone dipropionate relieves redness, swelling, itching and irritation of the skin.

Enstilar® is available only with a doctor’s prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

This medicine is not addictive.

Before you use Enstilar®

When you must not use Enstilar®

Do not use Enstilar® if you:

  • are allergic to calcipotriol, betamethasone dipropionate or any of the other ingredients listed at the end of this leaflet (see Product description) or any other similar medicine, such as topical corticosteroids
  • have high blood calcium levels (ask your doctor)
  • have other types of psoriasis known as generalised pustular or erythrodermic exfoliative psoriasis (your doctor will identify these conditions for you)

Some of the symptoms of an allergic reaction 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 Enstilar® on skin affected by:

  • viral, fungal, bacterial or parasitic skin infections
  • tuberculosis (TB)
  • perioral dermatitis (red rash around the mouth)
  • thin skin, easily damaged skin, stretch marks
  • ichthyosis (dry skin with fish like scales)
  • acne
  • rosacea
  • ulcers or broken skin

Inform your doctor if you are suffering from any illness before using Enstilar®.

Do not use Enstilar®

  • after the expiry date printed on the pack OR
  • if the can has been opened for more than 6 months OR
  • if the packaging is torn, doesn’t look quite right or shows signs of tampering.

If any of these apply, return the medicine to your pharmacist for disposal.

If you are not sure whether you should start using Enstilar®, talk to your doctor.

Before you start to use it

Tell your doctor if you have a known allergy to Enstilar® calcipotriol, betamethasone dipropionate or any of the ingredients listed at the end of this leaflet.

Tell your doctor if you

  • are pregnant
  • are breast-feeding
  • intend to breast feed.

Do not use Enstilar® in children. Safety and effectiveness of Enstilar® in those below 18 years of age has not been established.

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

Other medicines

Tell your doctor or pharmacist if you are using 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 you should be careful with or avoid whilst using Enstilar®.

How to use Enstilar®

Caution: Extremely flammable. Please read important information under ‘Storage’.

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.

Enstilar® is for topical use (on the skin). Before use, read the patient information, even if you have used Enstilar® before. Enstilar® is designed for direct application (spray on) to your skin, where it is affected by psoriasis.

Important: Do not use more than 15g in one day. 15g corresponds to the amount sprayed from the can when the actuator is fully pressed down for 1 minute. Do not use more than 100g in one week.

For example, no more than 2 cans in one week. One 60g can should last you at least 4 days.

If you also use other calcipotriol containing products (e.g.: Daivobet® gel or ointment, Daivonex®) for your psoriasis, then the total amount of calcipotriol products must not exceed 15g per day or 100 grams per week.

NOTE: If you use more than the recommended amount of Enstilar®, the levels of calcium in your blood may rise. This is known as “hypercalcaemia”.

Hypercalcaemia:

  • is measured by a blood test
  • may be harmful
  • may mean that Enstilar® or any other product containing calcipotriol (e.g.: Daivobet® gel or ointment, Daivonex®) should not be used until the calcium level has become normal again.

Blood calcium levels will quickly normalise when your doctor discontinues Enstilar® treatment.

How to use Enstilar®

Enstilar® should be applied to dry skin on the affected areas of the body.

  1. Shake the can before use and remove the cap.

  1. Apply the medication by holding the can at least 3cm (approximately 1.5 inches) from the skin and spray onto the affected area.

  1. The foam can be sprayed by holding the can in any orientation except horizontally. Apply a layer of foam only to the psoriasis plaques. Spray directly onto each affected skin area and gently rub in. If you accidentally put some of the foam on normal skin, wipe it off as soon as possible.

  1. Gently rub the foam into your affected skin areas
    You will need to repeat steps 1 to 4 until all of the affected areas are covered.

  1. After applying your medication, put the cap back on the can to prevent accidental pressing of the can when not in use.
  2. Wash your hands well after using Enstilar® (unless you are using the foam to treat your hands). This will avoid accidentally spreading the foam to other parts of your body (especially face, mouth and eyes).
  3. Take care not to get the foam spray in your eyes. If this happens, rinse your eyes with clean water and seek medical advice.
  4. If you accidentally put some of the foam onto skin not affected by psoriasis, wipe it off as soon as possible.
  5. Do not bandage, tightly cover or wrap the treated area

For best results leave on during the day or night. The treated area does not need to be covered. You may wear your usual clothes however avoid contact with fabric that is easily stained by grease (e.g. silk).

Do not use Enstilar®

  • on large areas of damaged skin;
  • in skin folds (eg. groin, underarm);
  • on the genitalia;
  • inside the mouth, nose or in the eyes;
  • on the face (an itchy red rash may develop).
  • under occlusive dressings (such as a bandage).

Wash your hands thoroughly after applying Enstilar® on any part of your body, unless your hands are being treated.

Thoroughly wash your hands prior to handling infants or children.

If any skin irritation develops, wash off the Enstilar®.

When to use Enstilar®

Apply Enstilar® once a day at the most convenient time for you, trying to applying it about the same time of the day each day (for example, morning, afternoon or evening).

As a guide on how much Enstilar® to use: A short 2 second spray of Enstilar® provides 0.5g of the medication and this amount should be sufficient to cover an area of skin roughly corresponding to the area of an adult hand.

How long to use it

Each treatment course would normally last for up to four weeks.

Your doctor may decide to stop treatment with Enstilar® once your psoriasis has improved, and to recommence it as needed. Your doctor may decide on a different treatment period and/or repeated treatment.

If you forget to use it

If you forget to use Enstilar®, use it as soon as you remember, then continue as before. Do not use an increased dose of the foam to make up for the forgotten doses.

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) 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. You may need urgent medical attention.

While you are using Enstilar®

Things you must do

While you are using Enstilar®, protect the treated skin areas from sunlight and Ultraviolet (UV) rays, for example, by wearing protective clothing. This is particularly important if your job or lifestyle means you spend time outdoors

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

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

Keep all appointments with your doctor so that your progress can be checked. Your doctor may do blood tests whilst you are using Enstilar® (or any other product containing calcipotriol, for example Daivobet® gel or ointment, Daivonex®). These tests check the levels of calcium in your blood and how well your kidneys are working (“renal function”).

Things you must not do

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

Do not use more than the recommended daily or weekly dose (see How to use Enstilar®).

Do not use other topical corticosteroids (e.g. Advantan®, Diprosone®, Elocon®) on areas treated with Enstilar®.

Side effects

As with all medicines, Enstilar® can cause some side effects.

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 Enstilar®
    or
  • if you notice any of the following and they worry you:
    - skin irritation (including itching, redness, dryness, swelling or peeling)
    - skin pain (including burning)
    - a rash on your face or body
    - a change in the colour of your skin
    - your skin is more sensitive to light
    - change in control of diabetes

Enstilar® contains butylated hydroxytoluene. This may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

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 Enstilar®

Keep Enstilar® in the box until required.

Storage

Keep Enstilar® in a cool dry place, store below 25°C.

CAUTION: Extremely flammable Pressurised container: May burst if heated. Protect from sunlight and do not expose to temperatures above 50°C. Do not pierce or burn, even after use. Do not spray on an open flame or other ignition source. Keep away from sparks, open flames and other ignition sources. Do not smoke while applying Enstilar®.

Keep Enstilar® in the box to protect from light.

Keep Enstilar® 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.

Disposal

Ask your pharmacist what to do with any Enstilar® that is left over if:

  • your doctor tells you to stop using Enstilar®, or
  • the can has been opened for more than 6 months or
  • the expiry date has passed.

Product description

What it looks like

Enstilar® is in a pressurised can. After spraying, a white to off-white foam is formed on the skin. The foam is a non-expanding foam, which gradually collapses after spraying.

Ingredients

Enstilar® contains the active ingredients:

  • calcipotriol (50 microgram/g) [as monohydrate]
  • betamethasone dipropionate (500 microgram/g).

It also contains:

  • liquid paraffin
  • polyoxypropylene-11 stearyl ether
  • dl-alpha-tocopherol
  • White soft paraffin
  • Butylated hydroxytoluene (included as an antioxidant in polyoxypropylene-11 stearyl ether)
  • Propellants: butane and methyl ether

The Australian Registration Number is AUST R 263292.

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

Supplier

Enstilar® is supplied in Australia by:

LEO Pharma Pty Ltd
Brisbane, QLD Australia

Toll free no: 1800 991 778

Web: www.leo-pharma.com.au

Enstilar, Daivobet, Daivonex, LEO and LEO/lion device are registered trademarks of LEO Pharma A/S.

This leaflet was prepared in May 2020.

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Enstilar

Active ingredient

Calcipotriol; Betamethasone

Schedule

S4

 

1 Name of Medicine

Calcipotriol monohydrate.
Betamethasone dipropionate.

6.7 Physicochemical Properties

Chemical structure.

Calcipotriol monohydrate.


Calcipotriol monohydrate is (5Z, 7E, 22E, 24S) -24-Cyclopropyl-9,10-secochola- 5,7,10(19),22-tetraene-1α,3β,24-triol monohydrate. The molecular weight of calcipotriol monohydrate is 430.6.
Calcipotriol is a white or almost white crystalline substance. It is freely soluble in ethanol, soluble in chloroform and propylene glycol, particularly insoluble in liquid paraffin. Solubility in water is 0.6 microgram/mL and the melting point is 166 to 168°C. Calcipotriol is a vitamin D derivative and behaves in a similar manner to vitamin D, forming a reversible temperature-dependent equilibrium between calcipotriol and pre-calcipotriol.

Betamethasone dipropionate.


Betamethasone dipropionate is 9-fluoro-11 β, 17, 21-trihydroxy-16 β-methylpregna-1,4- diene-3,20-dione 17,21-dipropionate. The empirical formula is C28H37FO7. The molecular weight of betamethasone dipropionate is 504.6.
Betamethasone dipropionate is a white or almost white, crystalline powder, practically insoluble in water, freely soluble in acetone and in methylene chloride, sparingly soluble in alcohol.

CAS number.

Calcipotriol monohydrate: 147657-22-5.
Betamethasone dipropionate: 5593-20-4.

2 Qualitative and Quantitative Composition

Enstilar contains 50 micrograms of calcipotriol (as monohydrate) and 500 micrograms of betamethasone (as dipropionate) per gram.

Excipients with known effect.

Butylated hydroxytoluene.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Foam Spray.
After spraying, a white to off white foam is formed. The foam has the appearance of non-expanding foam that gradually collapses after spraying.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antipsoriatics. Other antipsoriatics for topical use, calcipotriol, combinations. ATC code: D05AX52.

Mechanism of action.

Enstilar combines the pharmacological effects of calcipotriol hydrate as a synthetic vitamin D3 analogue and betamethasone dipropionate as a synthetic corticosteroid.
In combination, calcipotriol monohydrate and betamethasone dipropionate promote greater anti-inflammatory and antiproliferative effects than either component alone.

Pharmacodynamic effects.

Under maximum use conditions, in subjects with extensive psoriasis on the body and scalp treated for up to 4 weeks adrenal response to ACTH was determined by measuring serum cortisol levels. None of 35 subjects had suppressed serum cortisol levels at 30 or 60 minutes post-ACTH stimulation. Thus it appears that for Enstilar, the risk of adrenal suppression is low when applied to extensive psoriasis vulgaris for 4 weeks. Similarly, there was no indication of abnormal calcium metabolism following application of Enstilar to extensive psoriasis vulgaris for 4 weeks.

Clinical trials.

Efficacy.

The efficacy of once daily use of Enstilar has been investigated in three randomised, double blind or investigator blind, 4 week clinical trials including more than 1100 subjects with psoriasis on the body (also scalp in Trial Two) of at least mild severity according to the Physician's Global Assessment of disease severity (PGA), affecting at least 2% body surface area (BSA) and with a modified psoriasis area severity index (m-PASI) of a least 2. The Physician's Global Assessment is made using a 5 point scale (clear, almost clear, mild, moderate and severe) based on the average psoriatic lesion. The m-PASI is a composite score assessing severity (erythema, scale and induration) and affected area (excluding face and skin folds).
In Trial One, 426 subjects were randomised to either Enstilar or the foam vehicle.
In Trial Two, 302 subjects were randomised to either Enstilar, betamethasone dipropionate (BDP) in the foam vehicle or calcipotriol in the foam vehicle.
In Trial Three, 376 subjects were randomised to either Enstilar, Daivobet ointment, foam vehicle or ointment vehicle. See Table 2.
The primary endpoint was subjects with 'treatment success' ('clear' or 'almost clear' for subjects with at least moderate disease at baseline, 'clear' for subjects with mild disease at baseline) according to the PGA at week 4. See Table 3.
Results for the primary endpoint 'treatment success' (PGA) of body at week 4 showed Enstilar to be statistically significantly more effective than all the comparators included and responses were observed in all categories of baseline disease severity.
In Trial Two the effect of Enstilar on scalp psoriasis was investigated as the percentage of subjects with 'treatment success' according to the PGA of the scalp at week 4. See Table 4.
Enstilar was statistically significantly more effective compared to calcipotriol and also associated with a higher rate of treatment success than BDP but this comparison did not reach statistical significance.
The effect of once daily use of Enstilar on itch and itch related sleep loss was investigated in Trial One by assessments with a visual analogue scale (VAS) where the range was from 0 mm (no itch at all) to 100 mm (worst itch you can imagine). Only subjects who reported itch and itch related sleep loss at baseline were evaluated. See Figures 1 and 2.
Statistically significant differences of at least 70% reduction in both itch and itch related sleep loss were observed in favour of subjects receiving Enstilar compared to those receiving foam vehicle from day 3 and throughout the treatment period.
Quality of life was investigated in Trial One by means of the generic EQ-5D-5L and the dermatologically specific DLQI. Statistically significantly greater improvement in quality of life, measured by DLQI, was demonstrated for subjects receiving Enstilar compared to those receiving foam vehicle from week 1 and throughout the treatment period. Measured by EQ-5D-5L, a statistically significantly greater improvement in favour of subjects receiving Enstilar compared to those receiving foam vehicle was demonstrated at week 4.

5.2 Pharmacokinetic Properties

Absorption.

The extent of percutaneous absorption of the two active ingredients following topical application of Enstilar was determined in the HPA axis trial in subjects with extensive psoriasis vulgaris (see Pharmacodynamic effects). Calcipotriol and betamethasone dipropionate were below the lower limit of quantification in most samples from 35 patients treated once daily for 4 weeks for extensive psoriasis involving the body and scalp.
Calcipotriol was quantifiable at some time point in 1 subject, betamethasone dipropionate in 5 subjects and metabolites of calcipotriol and betamethasone dipropionate were detectable in 3 and 27 subjects respectively.

Distribution.

In rats, tissue distribution studies with radiolabelled calcipotriol and betamethasone dipropionate, respectively, showed that the kidney and liver had the highest level of radioactivity.

Metabolism.

Following systemic exposure, both active ingredients, calcipotriol and betamethasone dipropionate are rapidly and extensively metabolised.

Excretion.

The main route of excretion of calcipotriol is via faeces (rats and mini pigs) and for betamethasone dipropionate it is via urine (rats and mice).

5.3 Preclinical Safety Data

Genotoxicity.

Calcipotriol was not genotoxic in assays for gene mutations (Ames test and mouse lymphoma TK locus assay) or chromosomal damage (human lymphocyte chromosomal aberration or mouse micronucleus test). Betamethasone dipropionate was not genotoxic in the Ames mutagenicity assay, the mouse lymphoma TK locus assay or in the rat micronucleus test.

Carcinogenicity.

A dermal 2 year carcinogenicity study with calcipotriol in mice showed no indications of an increase in tumours at doses up to 30 microgram/kg/day (below the clinical dose on a body surface area basis).
In a 40 week study in which albino hairless mice were exposed to both ultraviolet radiation (UVR) and topically applied calcipotriol, a reduction in the time required for UVR to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UVR to induce skin tumours.
A 2 year oral carcinogenicity study was conducted with calcipotriol in rats at doses up to 15 microgram/kg/day. A treatment related increase in benign c-cell adenomas was observed in the thyroid of males at 15 microgram/kg/day and females that received ≥ 5 microgram/kg/day. A treatment related increase in benign pheochromocytomas was observed in the adrenal glands of males receiving 15 microgram/kg/day. The relevance of these findings to patients is unknown.
When betamethasone dipropionate was applied topically to mice for up to 24 months at doses up to 8.5 microgram/kg/day in females, and 12.9 microgram/kg/day in males or administered given orally to rats for up to 24 months at doses up to 200 microgram/kg/day (estimated exposures based on AUC of the metabolite betamethasone 17-propionate at least 70 times that expected in patients), no significant changes in tumour incidence were observed when compared to control.

4 Clinical Particulars

4.1 Therapeutic Indications

Topical treatment of psoriasis vulgaris in adults.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients.
Enstilar is contraindicated in erythrodermic and pustular psoriasis.
Due to the content of calcipotriol, Enstilar is contraindicated in patients with known disorders of calcium metabolism (see Section 4.4 Special Warnings and Precautions for Use, Effects on calcium metabolism).
Due to the content of corticosteroid, Enstilar is contraindicated in the following conditions if present in the treatment area: viral (e.g. herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds.

4.4 Special Warnings and Precautions for Use

For external use only.

Effects on endocrine system.

Adverse reactions found in connection with systemic corticosteroid treatment, such as adrenocortical suppression or impaired glycaemic control of diabetes mellitus may occur also during topical corticosteroid treatment due to systemic absorption.
Application under occlusive dressings should be avoided since it increases the systemic absorption of corticosteroids. Application on large areas of damaged skin, or on mucous membranes or in skin folds should be avoided since it increases the systemic absorption of corticosteroids.

Effects on calcium metabolism.

Due to the content of calcipotriol in Enstilar, hypercalcaemia may occur if the maximum weekly dose (100 g) is exceeded. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the maximum weekly dose of calcipotriol is not exceeded.

Local adverse reactions.

Enstilar contains a potent group III steroid and concurrent treatment with other steroids on the same treatment area must be avoided.
Skin of the face and genitals are very sensitive to corticosteroids. This product should not be used in these areas.
The patient must be instructed on correct use of the product to avoid application and accidental transfer to the face, mouth and eyes. Hands must be washed after each application to avoid accidental transfer to these areas, unless affected skin on the hands is being treated.
Enstilar contains butylated hydroxytoluene which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

Concomitant skin infections.

When lesions become secondarily infected, they should be treated with antimicrobial therapy. However, if the infection worsens, treatment with corticosteroids should be discontinued.

Discontinuation of treatment.

When treating psoriasis with topical corticosteroids, there may be a risk of rebound effects when discontinuing treatment. Medical supervision should therefore continue in the post-treatment period.

Long-term use.

Long term use of corticosteroids may increase the risk of local and systemic adverse reactions.
Treatment should be discontinued in case of adverse reactions related to long term use of corticosteroids.
While long-term safety and efficacy studies have not been conducted with Enstilar, long-term safety and efficacy data is available on the combination of calcipotriol and betamethasone dipropionate in ointment and gel formulations.

Unevaluated use.

There is no experience with the use of Enstilar in guttate psoriasis.

UV exposure.

During Enstilar treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Topical calcipotriol should be used with UVR only if the physician and patient consider that the potential benefits outweigh the potential risks.

Use in the elderly.

The safety and efficacy of Enstilar in elderly patients have not been established. No data are available.

Paediatric use.

Enstilar is not recommended for use in children and adolescents below 18 years of age due to the lack of data on safety and efficacy.

Effects on laboratory tests.

There are no data available on the effects of Enstilar on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed with Enstilar.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Possible effects of betamethasone dipropionate in combination with calcipotriol on fertility have not been investigated in animals. Studies in rats with oral doses of calcipotriol or betamethasone dipropionate demonstrated no impairment of male and female fertility.
(Category B3)
There are no adequate data from the use of Enstilar in pregnant women. Enstilar should only be used during pregnancy when the potential benefit clearly outweighs the potential risk. Studies of corticocorticoids in animals have shown reproductive toxicity (cleft palate, skeletal malformations). When pregnant rats were treated orally daily with betamethasone dipropionate from early gestation and throughout the lactation period, prolonged gestation (at ≥ 0.3 mg/kg/day), reduced offspring survival (at ≥ 0.1 mg/kg/day) and lower offspring weights (at 1 mg/kg/day) were observed. Studies of calcipotriol in animals have shown an increase in the incidence of skeletal variations in rats (wavy ribs, extra ribs, incomplete development of skull bones) at oral doses of 36 mg/kg/day. The relevance of these findings for humans is unknown.
Betamethasone passes into breast milk. It is unknown if topical application of Enstilar could result in sufficient systemic absorption to produce significant quantities of this corticosteroid in human breast milk. There are no data on the excretion of calcipotriol in breast milk.
Caution should be exercised when prescribing Enstilar to women who breastfeed. The patient should be instructed not to use Enstilar on the breast when breastfeeding.

4.8 Adverse Effects (Undesirable Effects)

Undesirable effects.

The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies.
The most frequently reported adverse reactions during treatment are application site reactions.
Adverse reactions are listed by MedDRA SOC and the individual adverse reactions are listed starting with the most frequently reported. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness (see Table 1).
Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1000 to < 1/100); Rare (≥ 1/10,000 to < 1/1000); Very rare (< 1/10,000).
The following adverse reactions are considered to be related to the pharmacological classes of calcipotriol and betamethasone, respectively.

Calcipotriol.

Adverse reactions include application site reactions, pruritus, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, psoriasis aggravated, photosensitivity and hypersensitivity reactions including very rare cases of angioedema and facial oedema.
Systemic effects after topical use may appear very rarely causing hypercalcaemia or hypercalciuria.

Betamethasone (as dipropionate).

Local reactions can occur after topical use, especially during prolonged application, including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid milia.
When treating psoriasis with topical corticosteroids, there may be a risk of generalised pustular psoriasis.
Systemic reactions due to topical use of corticosteroids are rare in adults; however, they can be severe. Adrenocortical suppression, cataract, infections, impaired glycaemic control of diabetes mellitus and increase of intraocular pressure can occur, especially after long-term treatment. Systemic reactions occur more frequently when applied under occlusion (plastic, skin folds), when applied on large areas and during long-term treatment.

Adverse reactions to excipients.

Enstilar contains butylated hydroxytoluene as an excipient, which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

Post marketing experience.

No data available at this time.

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: www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Enstilar is for topical use only. Do not use if the pack shows signs of damage or tampering.

Adults.

Enstilar should be applied to the affected area once daily. The recommended treatment period is 4 weeks. If it is necessary to continue or restart treatment after this period, treatment should be continued after medical review and under regular medical supervision.
The maximum daily dose of Enstilar should not exceed 15 g, i.e. one 60 g can should last for at least 4 days. 15 g corresponds to the amount administered from the can if the actuator is fully depressed for approximately one minute. A two-second application delivers approximately 0.5 g. As a guide, 0.5 g of foam should cover an area of skin roughly corresponding to the surface area of an adult hand.
The maximum weekly dose of Enstilar should not exceed 100 g. If using other calcipotriol containing products concomitantly, the total dose of all calcipotriol containing medical products, including Enstilar, should not exceed 15 g per day and 100 g per week.
The total body surface area treated should not exceed 30%.

Method of administration.

The can should be shaken before use. Enstilar should be applied by holding the can at least 3 cm (approximately 1.5 inches) from the skin and sprayed. The foam can be sprayed holding the can in any orientation except horizontally. Enstilar should be sprayed directly onto each affected skin area and rubbed in gently. The hands should be washed after using Enstilar (unless Enstilar is used to treat the hands) to avoid accidentally spreading to other parts of the body. It is recommended not to take a shower or bath immediately after application of Enstilar.

4.7 Effects on Ability to Drive and Use Machines

Enstilar has no or negligible influence on the ability to drive and to use machines.

4.9 Overdose

Usage above the recommended dose may cause elevated serum calcium which subsides when treatment is discontinued. The symptoms of hypercalcaemia include polyuria, constipation, muscle weakness, confusion and coma.
Excessive prolonged use of topical corticosteroids may result in adrenocortical suppression which is usually reversible. Symptomatic treatment may be indicated.
In case of chronic toxicity the corticosteroid treatment must be discontinued gradually.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only medicine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Liquid paraffin, polyoxypropylene-11 stearyl ether, dl-alpha-tocopherol, white soft paraffin, butylated hydroxytoluene (included as an antioxidant in polyoxypropylene-11 stearyl ether). Propellants: butane and methyl ether.

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.
Use within 6 months of opening.
Do not use beyond the expiry date on the package.

6.4 Special Precautions for Storage

Store below 25°C.
Caution: Extremely flammable. Pressurised container. May burst if heated. Protect from sunlight and do not expose to temperatures exceeding 50°C. Do not pierce or burn, even after use. Do not spray on an open flame or other ignition source. Keep away from sparks, open flames and other ignition sources. Do not smoke while applying Enstilar.

6.5 Nature and Contents of Container

Enstilar is contained in a white aluminium can fitted with a continuous valve and a polypropylene actuator with a frosted cap. The registered pack sizes are 60 g* and 2 x 60 g.
*Marketed pack size.

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