SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Calcipotriol Cream 50 micrograms/g

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

One gram of cream contains 0.05mg (is equal to 50 micrograms) of calcipotriol.

Excipient: Cetostearyl alcohol 60mg/g For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Cream White cream

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Calcipotriol cream is indicated for the topical treatment of mild to moderately severe psoriasis (psoriasis vulgaris).

4.2    Posology and method of administration

Adults:

As monotherapy

The calcipotriol cream should be applied to the affected skin on limbs or trunk once or twice daily. At the beginning of treatment, twice daily (morning and evening) application is recommended. For maintenance therapy, the frequency of application may be decreased to once daily, depending on the response.

Cream has to be applied as a thin layer to affected skin with gentle rubbing to cover the affected area until most of the cream disappears.

The maximum amount of cream applied should not exceed 100 grams per week. If it is used together with ointment or solution containing calcipotriol, the total weekly dose of calcipotriol should not exceed 5mg (for example 30ml of scalp solution plus 60g of cream or ointment).

The duration of therapy depends on the clinical appearance. A pronounced therapeutic effect is generally seen after a maximum of 4-8 weeks. Therapy can be repeated.

As combination therapy

Once daily application of calcipotriol cream in combination with topical corticosteroids (e.g. administration of calcipotriol cream in the morning and steroid in the evening) is effective and well tolerated.

Renal/hepatic impairment

Patients with known severe renal or liver impairment should not be treated with calcipotriol.

Children and adolescents (< 18 years) :

There is limited experience with the use of calcipotriol cream in children and adolescents. The efficacy and long-term safety of above mentioned dosage (under adults) has not been established in children and adolescents. Therefore its use in this population cannot be recommended.

4.3 Contraindications

-    Hypersensitivity to the active substance calcipotriol or to any of the excipients

-    Known disorders of calcium metabolism

-    Hypercalcaemia

4.4 Special warnings and precautions for use

Calcipotriol cream should not be used on the face.

Patients should be advised to wash their hands after applying the cream in order to prevent the inadvertent transfer to other areas, especially the face.

The efficacy and long-term safety of calcipotriol cream in children and adolescents has not been established. Therefore its use in this population cannot be recommended.

Hypercalcaemia may occur if the maximum weekly dose (100 g) is exceeded. However, serum calcium is quickly normalised when treatment is discontinued.

In view of a possible effect on calcium metabolism, patients should be advised to use no more than the recommended dose and the addition of penetration-promoting substances (such as salicylic acid) to the cream is not permitted. Occlusion is undesirable for the same reason.

The clinical symptoms of hypercalcaemia may resemble those of cholecalciferol overdose, i.e. the hypercalcaemia syndrome or calcium intoxication (see section 4.9), depending on the intensity and duration of the hypercalcaemia. Persistent hypercalcaemia may result in ectopic deposits of calcium in the blood vessel walls, joint capsules, gastric mucosa, cornea and renal parenchyma.

During calcipotriol 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 UV radiation only if the physician and patient consider that the potential benefits outweigh the potential risks (see section 5.3).

Patients with known severe renal or liver impairment should not be treated with this medicinal product due to limited experience.

Calcipotriol cream contains cetostearyl alcohol. It may cause local skin reactions (e.g. contact dermatitis).

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant administration of calcipotriol and salicylic acid externals may cause an inactivation of calcipotriol.

There is no experience of concomitant therapy with other antipsoriatic products applied to the same area of skin at the same time.

4.6    Pregnancy and lactation

Pregnancy:

For calcipotriol no data on pregnant patients are available. A limited absorption is expected after local application of this cream at small areas. If used as indicated no disturbance of the calcium homeostasis is to be expected. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure it is preferable to avoid the use of calcipotriol in pregnancy.

Lactation:

It is unknown whether calcipotriol is excreted in human breast milk. The excretion of calcipotriol in milk has not been studied in animals.

As a precautionary measure it is preferable to avoid the use of calcipotriol in lactation.

4.7    Effects on ability to drive and use machines

In view of the nature of the product and the indications for its use, no effect on the ability to drive and use machines is to be expected.

Undesirable effects

Based on the clinical data undesirable effects occurred in approximately 25% of the patients.

The most frequently reported undesirable effects are various transient skin reactions and in particular application site reactions, which seldom requires discontinuation of treatment.

The undesirable effects are listed by MedDra SOC and the individual undesirable effects are listed starting with the most frequently reported.

Metabolism and nutrition disorders

The following undesirable effects have been reported for calcipotriol cream, ointment and scalp solution during post-marketing experience: transient changes in skin pigmentation, transient photosensitivity reaction and hypersensitivity reaction including urticaria, angioedema, periorbital or facial oedema (very rarely). Perioral dermatitis may occur rarely. Based on post-marketing data the total ‘reporting rate’ of undesirable effects is very rare being approximately 1:10,000 treatment courses.

4.9 Overdose

Use above the recommended dose (see section 4.2) may cause elevated serum calcium which disappears rapidly after cessation of treatment.

The clinical signs of hypercalcaemia include anorexia, nausea, vomiting, constipation, hypotonia, depression, lethargy and coma.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other antipsoriatics for topical use, ATC code: D05AX02

Calcipotriol is a vitamin D derivative. In vitro data show that calcipotriol induces differentiation and suppresses proliferation of keratinocytes. The effect of calcipotriol in psoriasis is ascribed mainly to this.

An effect, first of all on the desquamation, then on the infiltration and finally on the erythema, is seen after two to four weeks of treatment. The maximum effect is usually achieved after six weeks.

5.2 Pharmacokinetic properties

Data from a single study containing 5 evaluable patients with psoriasis treated with 0.3 - 1.7 g of a 50 micrograms/g tritium labelled calcipotriol ointment suggested that less than 1% of the dose was absorbed. However, total recovery of the tritium label over a 96 hour period ranged from 6.7 to 32.6%, figures maximised by uncorrected chemiluminescence. There were no data on ³H tissue distribution or excretion from the lungs.

5.3 Preclinical safety data

The effect on calcium metabolism is approximately 100 times less than that of the hormonally active form of vitamin D₃.

A dermal carcinogenicity study in mice showed no indications of increased carcinogenic risks.

In another study where albino hairless mice were repeatedly exposed to both ultraviolet (UV) radiation and topically applied calcipotriol for 40 weeks at doses which correspond to 9, 30 and 90 pg/m²/day (equivalent to 0.25, 0.84 and 2.5 times the maximum recommended daily dose for a 60 kg adult, respectively), 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.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Disodium edetate

Disodium phosphate dihydrate

Sodium dihydrogen phosphate dihydrate

Chloroallylmethenamine chloride

Glycerol

Macrogol cetostearyl ether Cetostearyl alcohol Paraffin, light liquid Paraffin, white soft Water, purified

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years

After first opening: 3 months

6.4    Special precautions for storage

Do not store above 25°C. Do not freeze.

6.5    Nature and contents of container

Membrane closed aluminium tube with polypropylene screw cap.

Pack size: 30 gram

Membrane closed aluminium tube with polyethylene screw cap.

Pack sizes: 30 gram, 60 gram, 100 gram and 120 gram.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements

7    MARKETING AUTHORISATION HOLDER

Sandoz Limited Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8    MARKETING AUTHORISATION NUMBER

PL 04416/0707

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18/06/2007

10 DATE OF REVISION OF THE TEXT

05/06/2014