Consumer medicine information

Calcipotriol / Betamethasone Sandoz 50/500

Calcipotriol; Betamethasone dipropionate

BRAND INFORMATION

Brand name

Calcipotriol/Betamethasone Sandoz 50/500

Active ingredient

Calcipotriol; Betamethasone dipropionate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Calcipotriol / Betamethasone Sandoz 50/500.

What is in this leaflet?

This leaflet answers some common questions about using the medicine Calcipotriol / Betamethasone Sandoz ointment. 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 Calcipotriol / Betamethasone Sandoz ointment against the benefits it is expected to have for you.

If you have any concerns about using this medicine, talk to your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Calcipotriol / Betamethasone Sandoz 50/500 ointment is used for

Calcipotriol / Betamethasone Sandoz ointment is an anti-psoriasis medicine. Calcipotriol / Betamethasone Sandoz ointment contains two active ingredients:

  • Calcipotriol (related to Vitamin D);
  • Betamethasone dipropionate (a corticosteroid).

Calcipotriol / Betamethasone Sandoz ointment is used only on skin affected by plaque-type psoriasis. Psoriasis is a skin disorder in which skin cells are overactive. The calcipotriol in Calcipotriol / Betamethasone Sandoz ointment treats the overactive skin cells. The betamethasone dipropionate relieves redness, swelling, itching and irritation of the skin.

Calcipotriol / Betamethasone Sandoz ointment is used in the type of psoriasis, where "plaques" form in the skin. Plaques are raised, rough, reddened areas covered with fine, dry silvery scales. Plaques are usually about one to two centimetres across.

Calcipotriol / Betamethasone Sandoz ointment 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 Calcipotriol / Betamethasone Sandoz 50/500 ointment

When you must not use Calcipotriol / Betamethasone Sandoz ointment

Do not use Calcipotriol / Betamethasone Sandoz ointment if you have an allergy to:

  • calcipotriol
  • betamethasone dipropionate
  • any of the other ingredients listed at the end of this leaflet (see Product description)
  • any other similar medicine, such as topical corticosteroids.

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 Calcipotriol / Betamethasone Sandoz ointment for

  • severe widespread psoriasis
  • generalised pustular psoriasis
  • erythrodermic exfoliative psoriasis.

Your doctor will identify these conditions for you.

Do not use Calcipotriol / Betamethasone Sandoz ointment if you

  • have high blood calcium levels;
  • are taking calcium supplements, drugs to treat calcium deficiency, vitamin D supplements or vitamin D-like medicines, for example calcitriol;
  • have kidney or liver problems;
  • have any viral, fungal or bacterial skin infections
  • tuberculosis (TB) or syphilis
  • 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 Calcipotriol / Betamethasone Sandoz ointment.

Do not use Calcipotriol / Betamethasone Sandoz ointment

  • after the expiry date printed on the pack
  • if it is 12 months after the tube was first opened
  • if the packaging is torn, doesn't look quite right or shows signs of tampering.

If any of these apply, return Calcipotriol / Betamethasone Sandoz ointment to your pharmacist for disposal.

Do not breastfeed if you are using Calcipotriol / Betamethasone Sandoz ointment on your breasts.

If you are not sure whether you should start using Calcipotriol / Betamethasone Sandoz ointment, talk to your doctor.

Before you start to use it

Tell your doctor if you have a known allergy to Calcipotriol / Betamethasone Sandoz ointment, 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 Calcipotriol / Betamethasone Sandoz ointment in children. Safety and effectiveness of Calcipotriol / Betamethasone Sandoz ointment 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.

Tell your doctor if you are taking calcium supplements, drugs to treat calcium deficiency, vitamin D supplements or vitamin D-like medicines, for example calcitriol. Do not use Calcipotriol / Betamethasone Sandoz ointment if you are taking these.

Your doctor and pharmacist have more information on medicines you should be careful with or avoid whilst using Calcipotriol / Betamethasone Sandoz ointment.

How to use Calcipotriol / Betamethasone Sandoz 50/500 ointment

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 much to use

Apply enough ointment to completely cover the psoriasis plaques.

One fingertip unit (FTU) is enough to cover an area of skin twice the size of your palm. For example, if the area to be treated is 2 elbows and 2 knees, you may require up to 4 FTU's of ointment.

One fingertip unit (FTU) is the amount of ointment, squeezed out of a tube, from the tip of an adult's index finger to the first crease in the finger.

The area treated should not be more than 30% of the body surface.

Discuss this with your doctor.

Do not use more than 15 g in one day. For example, no more than half (1/2) of a 30 g tube in one day.

Do not use more than 100 g in one week. For example, no more than 3 tubes of 30 g in one week.

If you use other calcipotriol containing products on your body psoriasis, then the total amount of calcipotriol products must not exceed 15 g per day or 100 g per week and the total area treated should not exceed 30% of the total body surface.

NOTE: If you use more than the recommended amount of Calcipotriol / Betamethasone Sandoz ointment, 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 Calcipotriol / Betamethasone Sandoz ointment or any other product containing calcipotriol (e.g.; Daivonex®) should not be used until the calcium level has become normal again.

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

How to use Calcipotriol / Betamethasone Sandoz ointment

NOTE: unlike certain other skin preparations, which you use very sparingly, use Calcipotriol / Betamethasone Sandoz ointment as follows:

Apply Calcipotriol / Betamethasone Sandoz ointment only to the psoriasis plaques in a thin layer and gently rub in. If you accidentally put some of the ointment on normal skin, wash it off as soon as possible.

Do not use Calcipotriol / Betamethasone Sandoz ointment

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

The treated area does not need to have a special covering. You may wear your usual clothes.

Wash your hands thoroughly after applying Calcipotriol / Betamethasone Sandoz ointment on any part of your body, unless your hands are being treated.

Thoroughly wash your hands prior to handling infants or children.

Take care not to get Calcipotriol / Betamethasone Sandoz ointment in your eyes. If this happens, rinse your eyes with clean water and tell your doctor.

Avoid getting Calcipotriol / Betamethasone Sandoz ointment on your face, scalp, mouth or eyes accidentally (see above).

If any skin irritation develops, wash off the Calcipotriol / Betamethasone Sandoz ointment.

When to use Calcipotriol / Betamethasone Sandoz ointment preparations

Apply Calcipotriol / Betamethasone Sandoz ointment once a day (either morning or night), unless otherwise directed by your doctor.

How long to use it

Continue to use Calcipotriol / Betamethasone Sandoz ointment for as long as your doctor tells you. Each treatment course would normally last for up to four weeks.

Your doctor may decide to stop Calcipotriol / Betamethasone Sandoz ointment treatment once your psoriasis has improved, and to recommence it as needed.

If you forget to use it

If you forget to use Calcipotriol/Betamethasone Sandoz ointment, 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 (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. You may need urgent medical attention.

While you are using Calcipotriol / Betamethasone Sandoz 50/500 ointment

Things you must do

While you are using Calcipotriol/Betamethasone Sandoz ointment, protect the treated skin areas from sunlight and Ultra Violet (UV) rays, for example, by wearing protective clothing. This is particularly important if your job or lifestyle means you spend time out-of-doors.

If you are going to start any new medicine, tell your doctor and pharmacist that you are using Calcipotriol / Betamethasone Sandoz ointment.

If you become pregnant while using Calcipotriol / Betamethasone Sandoz ointment, 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 Calcipotriol/Betamethasone Sandoz ointment (or any other product containing calcipotriol). 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 Calcipotriol / Betamethasone Sandoz 50/500 ointment).

Do not use other topical corticosteroids (e.g. Advantan®, Diprosone®, Elocon®) on areas treated with Calcipotriol / Betamethasone Sandoz ointment.

Side effects

As with all medicines, Calcipotriol / Betamethasone Sandoz ointment 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 Calcipotriol / Betamethasone Sandoz ointment or if you notice any of the following and they worry you:

  • skin irritation
  • skin peeling
  • itching
  • skin burning sensation
  • skin shrinkage or wasting
  • rash on your face or body
  • worsening of psoriasis
  • infected hair roots
  • bruising of skin
  • skin pain
  • change in the colour of your skin
  • your skin is more sensitive to light
  • headache
  • back pain
  • change in control of diabetes mellitus.

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 Calcipotriol / Betamethasone Sandoz ointment

Keep Calcipotriol / Betamethasone Sandoz ointment in the box until required.

Storage

Keep your Calcipotriol / Betamethasone Sandoz ointment in a cool dry place where the temperature stays below 25°C. However, do not keep Calcipotriol / Betamethasone Sandoz ointment in the refrigerator, as the ointment will not spread easily.

Do not store Calcipotriol / Betamethasone Sandoz ointment 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 Calcipotriol / Betamethasone Sandoz ointment 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 Calcipotriol / Betamethasone Sandoz ointment that is left over if:

  • your doctor tells you to stop using Calcipotriol / Betamethasone Sandoz ointment
  • the tube has been opened for more than 12 months
  • the expiry date has passed.

Product description

What it looks like

Calcipotriol / Betamethasone Sandoz ointment is an off-white ointment.

Ingredients

Active ingredients:

  • calcipotriol (50 microgram/g)
  • betamethasone dipropionate (500 microgram/g).

Inactive ingredients:

  • liquid paraffin
  • oleyl alcohol
  • alpha-tocopherol
  • white soft paraffin

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

This leaflet was prepared in December 2020.

Australian Register Number:
30 g tube: AUST R 255532

Published by MIMS February 2021

BRAND INFORMATION

Brand name

Calcipotriol/Betamethasone Sandoz 50/500

Active ingredient

Calcipotriol; Betamethasone dipropionate

Schedule

S4

 

1 Name of Medicine

Calcipotriol and betamethasone (as dipropionate).

2 Qualitative and Quantitative Composition

Calcipotriol/Betamethasone Sandoz 50/500 is a combination ointment containing calcipotriol 50 microgram/g and betamethasone (as dipropionate) 500 microgram/g.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Calcipotriol/Betamethasone Sandoz 50/500 is an off-white ointment base.

4 Clinical Particulars

4.1 Therapeutic Indications

Calcipotriol and betamethasone ointment is indicated for the once daily topical treatment of plaque-type psoriasis vulgaris amenable to topical therapy.

4.2 Dose and Method of Administration

Calcipotriol/Betamethasone Sandoz 50/500 ointment is indicated for topical use only. Calcipotriol/Betamethasone Sandoz 50/500 ointment is not for ophthalmic use.
The phototoxic effects of calcipotriol and betamethasone ointment have not been studied in psoriasis patients. All psoriasis-affected areas treated with calcipotriol and betamethasone ointment should be, where possible, protected from direct sunlight and UV-light with items of clothing.

Adults.

Calcipotriol and betamethasone ointment should be applied topically to the affected area once daily. The maximum daily dose should not exceed 15 grams.
The maximum recommended weekly dose of calcipotriol and betamethasone ointment is 100 grams/week.
The treated area should not be more than 30% of the body surface.
The use of calcipotriol and betamethasone ointment should be intermittent for up to one year under close medical supervision. Treatment should be limited to four week periods with calcipotriol used alone for one month between periods of use of calcipotriol and betamethasone ointment as needed.

Children.

Calcipotriol and betamethasone ointment is not recommended for use in children and adolescents below the age of 18 years.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed, see Section 6.1 List of Excipients.
Patients with known disorders of calcium metabolism (see Section 4.4 Special Warnings and Precautions for Use).
Due to the corticosteroid content: viral lesions of the skin (e.g. herpes or varicella), fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis or syphilis, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulceration, wounds, perianal and genital pruritus.
Erythrodermic, exfoliative and pustular psoriasis.
Patients with severe renal insufficiency or severe hepatic disorders.
Not for ophthalmic use.

4.4 Special Warnings and Precautions for Use

For external use only.

Effects on calcium metabolism.

In view of the risk of hypercalcaemia secondary to excessive absorption of calcipotriol when there is extensive skin involvement, calcipotriol and betamethasone ointment should not be used on more than 30% of the body surface area.
The risk of hypercalcaemia is minimal when the recommendations relevant to calcipotriol are observed. In adults, the maximum dosage of 100 g ointment per week should not be exceeded.
Treatment with calcipotriol and betamethasone ointment in adults in the recommended amounts up to 100 g per week does not generally result in changes in laboratory values.
Serum calcium and renal function should be monitored at 3 monthly intervals during periods of usage of topical calcipotriol, including that in calcipotriol and betamethasone ointment. If the serum calcium level is elevated, treatment with calcipotriol and betamethasone ointment should be discontinued and the condition should be treated appropriately. The levels of serum calcium should be measured once weekly until the serum calcium levels return to normal values.

Local adverse reactions.

As calcipotriol and betamethasone ointment contains a potent corticosteroid (classified as WHO group III steroid), concurrent treatment with other steroids should be avoided.
Skin of the face and genitals are very sensitive to corticosteroids. Long term treatment of these parts of the body should be avoided. These areas should only be treated with the weaker corticosteroids.
The patient must be instructed on correct use of the product to avoid application and/or accidental transfer to the scalp, face, mouth or eyes. Calcipotriol and betamethasone ointment is not recommended for use on the face since it may give rise to itching and erythema of the facial skin. Treatment of more than 30% of the body surface should be avoided. Repeated treatment of large body surface areas may result in adverse effects. Patients should be instructed to wash their hands after using calcipotriol and betamethasone ointment, to avoid inadvertent transfer of ointment to the face from other body areas.

Effects on endocrine system.

Adverse effects found in connection with systemic corticosteroid treatment, such as adrenocortical suppression or impact on the metabolic control of diabetes mellitus, may occur also during topical corticosteroid treatment due to its systemic absorption.
Application of calcipotriol and betamethasone ointment to large areas of damaged skin, under occlusive dressings, to mucous membranes, or in skin folds should be avoided as these conditions increase the systemic absorption of both corticosteroids and calcipotriol. Elevated systemic absorption of calcipotriol could, as previously mentioned, result in hypercalcaemia in some patients.

Concomitant skin infections.

If lesions become secondarily infected, they should be treated with antimicrobial therapy. However, if infection worsens, treatment with topical corticosteroids should be withdrawn.

Discontinuation of treatment.

When treating psoriasis with topical corticosteroids there may be a risk of generalised pustular psoriasis. There may be a risk of rebound when discontinuing long-term treatment with corticosteroids. Medical supervision should therefore continue in the post-treatment period.

Unevaluated use.

There is no experience of the use of calcipotriol and betamethasone ointment on the scalp.

Concurrent treatment and UV exposure.

The stability of calcipotriol in sunlight and UV light has not been demonstrated. No clinical trials have been conducted with calcipotriol-containing products in Australia, where there is a particularly high potential to be exposed to high levels of UV radiation. In addition, the phototoxic effects of calcipotriol and betamethasone ointment have not been studied in psoriasis patients.
Therefore, treated skin areas should be protected from sunlight and UV light (using physical covering and/or sunscreens), particularly where exposure may be considerable for reasons such as occupation. Topical calcipotriol should be used with UVR only if the physician and patient consider that the potential benefits outweigh the potential risks.

Long-term use.

The recommended treatment period of calcipotriol and betamethasone ointment is 4 weeks under medical supervision, for up to 52 weeks. There is clinical trial experience with intermittent 4 weekly cycles of calcipotriol and betamethasone ointment and calcipotriol alone used between treatment cycles (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.2 Dose and Method of Administration).
With long-term use there is an increased risk of local and systemic corticosteroid adverse effects. Excessive prolonged use of topical corticosteroids may suppress the hypothalamic pituitary adrenal axis (HPA). The treatment should be discontinued in case of adverse effects related to long-term use of corticosteroids as described, see Section 4.8 Adverse Effects (Undesirable Effects).

Use in hepatic impairment.

Safety has not been established in patients with hepatic impairment. Calcipotriol and betamethasone ointment is contraindicated in patients with severe hepatic impairment.

Use in renal impairment.

Safety has not been established in patients with renal impairment. Calcipotriol and betamethasone ointment is contraindicated in patients with severe renal impairment.

Use in the elderly.

Clinical experience has not identified any differences in response in elderly patients (65 years and older). However, greater sensitivity of some elderly individuals cannot be ruled out.

Paediatric use.

Calcipotriol and betamethasone ointment is not recommended for use in children and adolescents below 18 years of age as the safety and effectiveness of calcipotriol and betamethasone ointment in this population has not been established.

Effects on laboratory tests.

There are no data available on the effects of calcipotriol and betamethasone ointment on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There is no experience with concurrent use of calcipotriol and betamethasone ointment and other anti-psoriatic products applied locally or systemically or with phototherapy.
Calcipotriol and betamethasone ointment should not be used concurrently with calcium or vitamin D supplements, or with drugs that enhance the systemic availability of calcium. No other drug interactions are known.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Possible effects of betamethasone in combination with calcipotriol on fertility have not been investigated in animals. Studies of the oral administration of calcipotriol in rats have shown no impairment of fertility.
(Category B1)
There are no adequate data from the use of calcipotriol and betamethasone ointment in pregnant women. Calcipotriol and betamethasone ointment should only be used during pregnancy when the potential benefit clearly outweighs the potential risk.
Studies of corticosteroids in animals have shown reproductive toxicity (cleft palate, skeletal malformations). Long-term oral administration of corticosteroids in rats has been shown to prolong gestation and make labour more difficult and prolonged. A reduction in postnatal survival and growth was observed in the offspring of these rats. 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 18 mg/kg/day and in rabbits (reduced skeletal ossification) at oral doses of 36 mg/kg/day. The relevance of these findings for humans is unknown.
 Betamethasone is excreted into breast milk. It is unknown if topical application of calcipotriol and betamethasone ointment 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 calcipotriol and betamethasone ointment to breast-feeding women. Application of calcipotriol and betamethasone ointment to the breast area should be avoided. Calcipotriol and betamethasone ointment should only be used during lactation if the potential benefits clearly outweigh the potential risks.

Note.

In order to avoid possible direct ingestion by infants, calcipotriol and betamethasone ointment should not be applied to the chest area of breast feeding women. After applying calcipotriol and betamethasone ointment to her skin, mothers should wash their hands thoroughly prior to handling her infant child.

4.7 Effects on Ability to Drive and Use Machines

Calcipotriol and betamethasone ointment has no or negligible influence on the ability to drive and to use machines.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

Adverse events reported in more than 1% of subjects enrolled in early clinical trials with calcipotriol and betamethasone ointment (in total 912 patients exposed to twice daily applications and 1286 patients exposed to once daily applications) are listed in Table 1.
A safety study in 634 patients with at least moderate psoriasis has investigated repeated courses of calcipotriol and betamethasone ointment used once daily as required, either alone or alternating on a four week basis with calcipotriol ointment, for up to 52 weeks, compared with calcipotriol ointment used alone for 48 weeks after an initial 4 week course of calcipotriol and betamethasone ointment. The number of patients who were exposed to intermittent treatment for 52 weeks was 112 in the calcipotriol and betamethasone ointment group, 117 in the calcipotriol and betamethasone ointment/calcipotriol ointment alternating group and 96 in the calcipotriol ointment group. Adverse drug reactions were reported by 21.7% of the patients in the calcipotriol and betamethasone ointment group, 29.6% in the calcipotriol and betamethasone ointment/ calcipotriol ointment alternating group and 37.9% in the calcipotriol ointment group. Adverse drug reactions reported in 1% or more of the patients are listed in Table 2.
Adverse effects of concern, possibly related to long-term corticosteroid use were reported by 4.8% of the patients in the calcipotriol and betamethasone ointment group, 2.8% in the calcipotriol and betamethasone ointment/calcipotriol ointment alternating group and 2.9% in the calcipotriol ointment group.
The effects of calcipotriol and betamethasone ointment on calcium metabolism and HPA function with long term use in psoriasis patients were not adequately studied.
In total, the clinical trial programme for calcipotriol and betamethasone ointment has so far included more than 2500 patients, and has shown that approximately 10% of patients can be expected to experience a non serious adverse effect (see Post-marketing use section for more details).

Post-marketing use.

Definition of frequency of adverse events: Very common > 1/10; Common > 1/100 and < 1/10; Uncommon > 1/1,000 and < 1/100; Rare > 1/10,000 and < 1/1,000; Very rare < 1/10,000.
Based on the above frequency definition, data from clinical trials and post market use show that the common adverse events, in the order of most frequently reported, are pruritus, rash and burning sensation of the skin. Additional uncommon adverse events, in the order of most frequently reported include skin pain or irritation, dermatitis, erythema, exacerbation of psoriasis, folliculitis and application site pigmentation changes.
Pustular psoriasis and photosensitivity are rare undesirable effects.
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 3.
Single cases of serious and life threatening undesirable effects including adrenal suppression and pustular psoriasis have been reported after prolonged use (2 years or more).

Adverse reactions associated with pharmacological classes.

The following adverse events are considered to be related to the pharmacological classes of calcipotriol and betamethasone, respectively.

Calcipotriol.

Potential adverse events include application site reactions, pruritus, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, and aggravation of psoriasis, transient photosensitivity, transient changes in skin pigmentation and allergic and hypersensitivity reactions including very rare cases of angioedema and facial oedema.
After topical use, systemic effects, causing hypercalcaemia or hypercalciuria may appear very rarely (see Section 4.4 Special Warnings and Precautions for Use).

Betamethasone (as dipropionate).

This product contains a potent corticosteroid.
Local reactions can occur after topical corticosteroid use, especially during prolonged application, including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid milia.
When used for the treatment of psoriasis, there may be the risk of generalised pustular psoriasis. There may be a risk of rebound when discontinuing long term treatment with corticosteroids.
Systemic effects due to topical use of corticosteroids are rare, in adults, however, they can be severe. HPA suppression, hypercalcaemia, cataract, infections, impact on metabolic control of diabetes mellitus and increase in intra-ocular pressure can occur, especially after long term treatment. Systemic effects occur more frequently when applied under occlusion (e.g. plastic, skin folds), when applied on large areas or during long treatment (see Section 4.4 Special Warnings and Precautions for Use).

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.

4.9 Overdose

Use at more than the recommended dose may cause elevated serum calcium, which rapidly subsides when treatment is discontinued. The symptoms of hypercalcaemia include polyuria, constipation, muscle weakness, confusion and coma. In such cases, the monitoring of serum calcium levels once weekly until the serum calcium returns to normal levels is recommended.
Excessive prolonged use of topical corticosteroids may suppress the hypothalamic pituitary adrenal axis (HPA) resulting in secondary adrenal insufficiency, which is usually reversible. In such cases symptomatic treatment is indicated.
In case of chronic toxicity the topical corticosteroid treatment must be withdrawn gradually.
It has been reported that due to misuse one patient with extensive erythrodermic psoriasis treated with 240 g of calcipotriol and betamethasone ointment per week (maximum recommended dose is 100 g per week) for 5 months developed Cushing's syndrome and after abruptly stopping treatment, developed pustular psoriasis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Calcipotriol is a non-steroidal antipsoriatic agent, derived from vitamin D. Calcipotriol exhibits a vitamin D-like effect by competing for the 1,25(OH)2D3 receptor. Calcipotriol is as potent as 1,25(OH)2D3, the naturally occurring active form of vitamin D, in regulating cell proliferation and cell differentiation, but much less active than 1,25(OH)2D3 in its effect on calcium metabolism. Calcipotriol induces differentiation and suppresses proliferation (without any evidence of a cytotoxic effect) of keratinocytes, thus reversing the abnormal keratinocyte changes in psoriasis. The therapeutic goal envisaged with calcipotriol is thus a normalisation of epidermal growth.
Betamethasone dipropionate is a potent topically-active corticosteroid producing prompt, marked and prolonged anti-inflammatory, antipruritic, vasoconstrictive and immunosuppressive properties, without curing the underlying condition. These effects can be enhanced under occlusive conditions due to increased penetration of stratum corneum (by approximately a factor of 10). The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear.

Clinical trials.

The pivotal clinical trials with calcipotriol and betamethasone ointment undertaken in adults are summarised below.
Topical treatment of psoriasis in adults using combination of calcipotriol 50 microgram/g plus betamethasone (as dipropionate) 500 microgram/g ointment regimen.
Two double-blind, multicentre, randomised, vehicle-controlled studies assessed the efficacy and safety of the combination calcipotriol 50 microgram/g plus betamethasone (as dipropionate) 500 microgram/g ointment once daily vs. calcipotriol ointment 50 microgram/g or betamethasone (as dipropionate) 500 microgram/g ointment alone once daily in patients with psoriasis. The study duration was 4 weeks. The primary efficacy endpoint was the percentage reduction of the Psoriasis Area and Severity Index (PASI) score. In both studies (MCB 0003 INT, MCB 9905 INT) there was a statistically significant difference (p < 0.001) favouring combination group administered once daily. There was no significant difference (p = 0.052) when combination therapy was used once daily compared to twice daily after 4 weeks of treatment (MCB 9905 INT). See Table 4.

5.2 Pharmacokinetic Properties

Clinical studies with radiolabelled ointment demonstrated less than 1% (95% CI: -0.1% to 0.3%) of calcipotriol and betamethasone from the applied dose (2.5 g) was systemically absorbed when applied to normal skin (625 cm2) for 12 hours. When the skin is damaged absorption was increased (~24% of applied dose). Application to psoriasis plaques and under occlusive dressings may increase the absorption of topical corticosteroids. Approximately 64% of the absorbed dose is protein bound. Plasma elimination half-life after intravenous administration is 5 to 6 hours. Elimination after dermal application is in order of days due to the formation of a depot in the skin.

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).

Carcinogenicity.

The carcinogenic or mutagenic potential of topical corticosteroids has not been investigated in animal studies.
A dermal carcinogenicity study with calcipotriol in mice showed no indications of increased carcinogenic risks. Calcipotriol solution was applied topically for up to 24 months at doses of 3, 10 and 30 microgram/kg/day (corresponding to 9, 30 and 90 microgram/m2/day). The high-dose was considered to be the Maximum Tolerated Dose for dermal treatment of mice with calcipotriol. Survival was decreased at 10 and 30 microgram/kg/day, particularly in the males. The reduced survival was associated with an increased incidence of renal lesions. This is an expected effect of treatment with high doses of calcipotriol or other vitamin D analogues. There were no dermal effects and no dermal or systemic carcinogenicity.
In a study where albino hairless mice were repeatedly exposed to both ultraviolet (UV) radiation and topically applied calcipotriol for 40 weeks at the same dose levels as in the dermal calcipotriol carcinogenicity study, a reduction in the time required for UV radiation to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UV radiation to induce skin tumours. The clinical relevance of these findings is unknown.
No carcinogenicity or photocarcinogenicity studies have been performed with betamethasone dipropionate.

6 Pharmaceutical Particulars

6.1 List of Excipients

Liquid paraffin, oleyl alcohol, di-alpha-tocopherol, and white soft paraffin.

6.2 Incompatibilities

Incompatibilities were either not assess 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.
Discard the unused product 12 months after first opening.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

It is available in a tube of 30 grams.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Calcipotriol.

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.

Chemical structure.


Chemical name: (5Z,7E,22E,24S)-24-Cyclopropyl-9,10-secochola- 5,7,10(19),22-tetraene-1α,3β,24-triol.
Molecular formula: C27H40O3.
Molecular weight: 412.6.

Betamethasone dipropionate.

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.

Chemical structure.


Chemical name: 9-Fluoro-11β -hydroxy-16β- methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate.
Molecular formula: C28H37FO7.
Molecular weight: 504.6.

CAS number.

Calcipotriol.

112965-21-6.

Betamethasone dipropionate.

5593-20-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes