SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Calcipotriol Ointment 50micrograms/g

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

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

Excipient: Propylene glycol 10 mg/g For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Ointment

White to off-white ointment.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Calcipotriol Ointment 50micrograms/g is indicated for    the topical treatment of mild

to moderately severe psoriasis (psoriasis vulgaris).

4.2    Posology and method of administration

Posology

Adults:

As monotherapy

Calcipotriol Ointment 50micrograms/g 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.

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

The maximum amount of ointment applied should not exceed 100 grams per week. If it is used together with cream or solution containing calcipotriol, the total weekly dose of calcipotriol should not exceed 5 mg (for example 40 ml scalp solution plus 60 g 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 in combination with topical corticosteroids (e.g. administration of Calcipotriol Ointment 50micrograms/g 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 (under 18 years)

There is limited experience with the use of calcipotriol ointment 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 or to any of the excipients listed in section 6.1.

•    Patients with severe renal or liver impairment

•    Known disorders of calcium metabolism or treatment with other medicinal products which increase serum calcium level.

•    Hypercalcaemia

4.4 Special warnings and precautions for use

Calcipotriol Ointment 50micrograms/g should not be used on the face.

Patients should be advised to wash their hands after applying the ointment and to avoid inadvertent transfer to other body areas, especially the face.

Patients should be advised to use no more than the maximum weekly dose since hypercalcaemia, which rapidly reverses on cessation of treatment, may occur.

The risk of hypercalcaemia is minimal when the dosage recommendations are followed.

Care should be exercised in patients with other types of psoriasis, since hypercalcaemia has been reported in patients with generalised pustular or erythrodermic exfoliative psoriasis.

Hypercalcaemia may occur if the maximum weekly dose (60 ml) 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 ointment 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 Ointment 50micrograms/g contains propylene glycol (may cause skin irritations).

Paediatric population

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

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 Fertility, pregnancy and lactation

Pregnancy:

The safety of the use of calcipotriol during human pregnancy has not been established. Studies in animals have shown reproductive toxicity when calcipotriol was administered orally (see section 5.3). Topically applied calcipotriol is slightly systemically absorbed, but a disruption of calcium homeostasis is not expected. As a precautionary measure, it is preferable to avoid the use of Calcipotriol in pregnancy.

Lactation:

It is unknown whether calcipotriol is excreted in breast milk.

Short-term use on small surfaces is not expected to lead to a relevant systemic absorption and no effects on the breastfed child are anticipated. In all other cases, breastfeeding is not recommended during treatment with calcipotriol.

Fertility:

There are no data on the effect of calcipotriol therapy on human fertility.

4.7    Effects on ability to drive and use machines

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

4.8    Undesirable effects

Based on the clinical data approximately 25% of the patients treated with calcipotriol could experience an adverse reaction. These reactions are usually mild.

The most frequently reported undesirable effects are various transient skin reactions in particular lesional/perilesional irritation.

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

Immune system disorders

Metabolism and nutrition disorders

Skin and subcutaneous tissue disorders

Very common (>1/10)	Skin irritation
Common (>1/100 to <1/10)	Pruritus, skin burning sensation, skin stinging sensation, skin dry, erythema, rash (including erythematous, maculo-papular, pustular and bullous reactions)
Uncommon (>1/1,000 to	Eczema, contact dermatitis, aggravated psoriasis

<1/100)
Very rare (<1/10,000)	Transient changes in skin pigmentation, transient photosensitivity, facial and perioral dermatitis

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

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 - 1.7g 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.

Calcipotriol has shown maternal and foetal toxicity in rats and rabbits when given by the oral route at doses of 54 pg/kg/day and 12 pg/kg/day, respectively. The foetal abnormalities observed with concomitant maternal toxicity included signs indicative of skeletal immaturity (incomplete ossification of the pubic bones and forelimb phalanges, and enlarged fontanelles) and an increased incidence of supernumerary ribs.

The significance for humans is unknown.

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

Macrogol stearyl ether Disodium edetate Disodium phosphate dihydrate a-Tocopheryl acetate Propylene glycol (E490) Paraffin, light liquid Water, purified Paraffin, white soft

6.2 Incompatibilities

Not applicable.

Shelf life

2 years

After first opening: 3 months

6.4 Special precautions for storage

Do not store above 25°C.

Do not refrigerate or freeze.

Store in the original package.

6.5. Nature and contents of container

Membrane closed aluminium tube with polypropylene screw cap. Packsize: 30 gram

Membrane closed aluminium tube with polyethylene screw cap. Packsizes: 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

MARKETING AUTHORISATION NUMBER(S)

PL 04416/0700

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/04/2007

10    DATE OF REVISION OF THE TEXT

13/07/2016