CALCIPOTRIOL 50 MICROGRAMS / ML SCALP SOLUTION - summary of medicine characteristics

Calcipotriol 50 micrograms/ml Scalp Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of cutaneous solution contains 0.05 mg (is equal to 50 micrograms) of calcipotriol.

Excipients with known effect:

Each ml of cutaneous solution contains 30 mg of propylene glycol and 0.00052 mmol (0.0119 mg) of sodium.

For the full list of excipients, see section 6.1.

Cutaneous solution.

Clear, colourless solution with an odour of menthol.

4.1 Therapeutic indications

Calcipotriol 50 micrograms/ml Scalp Solution is indicated for the topical treatment of mild to moderate scalp psoriasis (psoriasis vulgaris).

4.2 Posology and method of administration

Posology

Adults

As monotherapy

Calcipotriol 50 micrograms/ml Scalp Solution should be applied to the affected areas twice daily (morning and evening). At beginning of treatment, twice daily application is recommended. For maintenance therapy, the frequency of application may be decreased to once daily, depending on the response.

The maximum weekly dose should not exceed 60 ml.

If this solution is used together with cream or ointment containing calcipotriol, the total weekly dose of calcipotriol should not exceed 5 mg (for example 60 ml of Calcipotriol 50 micrograms/ml Scalp Solution plus 40 g of cream or ointment.

The duration of treatment 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 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 of age)

There is limited experience with the use of calcipotriol solution in children and adolescents.

The efficacy and long-term safety of above mentioned dose (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

Effects on calcium metabolism

Due to the content of calcipotriol, hypercalcaemia may occur if the maximum weekly dose is exceeded (see section 4.2).

Serum calcium is normalised when treatment is discontinued.

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

Local adverse reactions

Calcipotriol should not be used on the face, as it may cause skin irritation. The patient must be instructed in correct use of the product to avoid accidental transfer to the face and eyes. Hands must be washed after each application to avoid accidental transfer to these areas.

Calcipotriol should be used with caution in skin folds as this may increase the risk of side effects (see section 4.8).

UV exposure

During treatment with calcipotriol, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. 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).

Unevaluated use

Due to lack of data, Calcipotriol should be avoided in guttate, erythrodermic and pustular psoriasis.

Due to lack of data, calcipotriol should be avoided in patients with severe liver and kidney disease (see section 4.3).

Calcipotriol 50 micrograms/ml Scalp Solution contains 30 mg propylene glycol per ml of solution.

Propylene glycol may cause skin irritation.

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 use with systemic vitamin D products, calcium supplements, or other agents that can increase serum calcium concentrations such as thiazide diuretics, estrogens, anabolic steroids, and parathyroid hormone or parathyroid hormone analogs may increase the risk of clinically significant hypercalcemia.

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 <product name> 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. Under these conditions, calcipotriol can be used during breastfeeding. Calcipotriol should not be applied to the breast during breastfeeding.

For long-term treatment and/or treatment of larger surfaces with calcipotriol, breastfeeding is not recommended.

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

The most frequently reported adverse reactions during treatment are various skin reactions, like pruritus and skin exfoliation.

Systemic reactions (hypercalcaemia and hypercalciuria) have been reported.

The risk of developing such reactions increases if the recommended total dose is exceeded (see section 4.4).

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

Frequency of adverse reactions is defined as:

Very common (>1/10),

Common (>1/100 to <1/10),

Uncommon (>1/1,000 to <1/100),

Rare (>1/10,000 to < 1/1,000),

Very rare (<1/10,000),

Not known (cannot be estimated from the available data).

The estimation of the frequency of adverse reactions is based on pooled analysis of data from clinical studies and spontaneous reporting.

Infections and infestations___________­________________________­_________________________

Immune system disorders

Metabolism and nutrition disorders

Skin and subcutaneous tissue disorders

Renal and urinary disorders___________­_________________

Uncommon__Hyper­calciuria

General disorders and administration site conditions

* Various types of rashes such as rash erythematous, rash maculo-papular, rash morbilliform, rash papular and rash pustular have been reported.

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 or search for MHRA Yellow Card in Google play or Apple App store).

4.9 Overdose

Use above the recommended dose may cause elevated serum calcium which quickly subsides when treatment is discontinued.

The symptoms of hypercalcemia include polyuria, constipation, muscle weakness, confusion and coma

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antipsoriatics, antipsoriatics for topical use, other antipsoriatics for topical use, ATC code: D05AX02

Calcipotriol is a vitamin D derivative. In vitro data suggest 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

No data are available on the absorption of calcipotriol following use of the scalp solution.

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 revealed no special hazards for humans.

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

The significance for humans is unknown.

In another studv where albino hairless mice were repeatedlv exposed to both ultraviolet (UV) radiation and topicallv applied calcipotriol for 40 weeks at doses which correspond to 9, 30 and 90 |ig/m2/day (equivalent to 0.25, 0.84 and 2.5 times the maximum recommended dailv dose for a 60 kg adult, respectivelv), a reduction in the time required for UV radiation to induce the formation of skin tumours was observed (statisticallv significant in males onlv), suggesting that calcipotriol mav 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

Sodium citrate

Hypromellose

Propylene glycol

Isopropyl alcohol

Levomenthol

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 refrigerate or freeze.

Keep the bottle in the outer carton in order to protect from light.

6.5 Nature and contents of container

Polyethylene bottle fitted with polyethylene nozzle and closed with polypropylene screw cap.

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

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Sandoz Limited

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 04416/0888

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

13/05/2009