LEO Pharma

Dovonex^® 50 micrograms/g Cream

Each gramme contains 50 micrograms of calcipotriol (as the hydrate).

For excipients, see 6.1

Cream

Soft white cream.

Dovonex^® Cream is indicated for the topical treatment of plaque psoriasis (psoriasis vulgaris). Dovonex^® cream may also be used in combination with topical corticosteroids.

Adults:

The cream should be applied to the affected area once to twice daily. Twice daily application of the cream is often preferred initially. Application of the cream can be reduced to once daily when appropriate. Maximum weekly dose should not exceed 100 g.

Dovonex^® Cream in combination with corticosteroids (e.g. administration of Dovonex^® in the morning and steroid in the evening) is effective and well tolerated.

Children:

Over 12 years:

Dovonex^® Cream should be applied to the affected area twice daily. Maximum weekly dose should not exceed 75 g.

Aged 6 to 12 years:

Dovonex^® Cream should be applied to the affected area twice daily. Maximum weekly dose should not exceed 50 g.

Under 6 years:

There is limited experience of the use of Dovonex^® Cream in this age group. A maximum safe dose has not been established.

There is no experience of use of Dovonex^® in combination with other psoriasis therapies in children.

Known hypersensitivity to any of the ingredients.

Due to the content of calcipotriol Dovonex^® is contraindicated in patients with known disorders of calcium metabolism.

Dovonex^® cream should not be used on the face. The patient must be instructed in correct use of the product to avoid application and accidental transfer to the face. Hands must be washed after each application.

Use of Dovonex^® should be avoided in patients with severe renal insufficiency or severe hepatic disorders.

The risk of hypercalcaemia is minimal when the dosage recommendations are followed. Hypercalcaemia may occur if the maximum weekly dose (100 g) is exceeded. However, serum calcium is quickly normalised when treatment is discontinued.

During Dovonex® treatment physicians may wish 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).

Cetostearyl alcohol may cause local skin reactions.

None known.

Safety for use of calcipotriol during human pregnancy and lactation has not been established. Studies in animals have not shown teratogenic effects. It is not known whether calcipotriol is excreted in breast milk. Calcipotriol should not be used during pregnancy and lactation unless clearly necessary.

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

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

The most frequently reported undesirable effects are various skin reactions and in particular application site reactions. Hypercalcaemia and allergic reactions have been reported very rarely.

Based on clinical data for Dovonex^® cream undesirable effects occurred in approximately 25% of the patients.

Pruritus, skin irritation (especially if accidentally transferred to face), burning and stinging sensation, dry skin, erythema and rash are common. Contact dermatitis, eczema and psoriasis aggravated are uncommon.

Systemic effects after topical use may appear very rarely causing hypercalcaemia or hypercalciuria, cf. section 4.4.

Post-market data on Dovonex^® cream, ointment and scalp solution.

Transient changes in skin pigmentation, transient photosensitivity reactions and hypersensitivity reactions including urticaria, angioedema, periorbital or face oedema have been reported very rarely. Perioral dermatitis may occur rarely.

Based on post-marketing data the total 'reporting rate' of undesirable effect is very rare being approximately 1:10,000 treatment courses.

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

Skin and subcutaneous tissue disorders

Pruritus

Skin burning sensation

Skin stinging sensation

Skin irritation

Skin dry

Erythema

Rash*

Eczema

Dermatitis contact

Psoriasis aggravated

Skin hyperpigmentation

Skin depigmentation

Photosensitivity reaction

Urticaria

Face oedema

Periorbital oedema

Angioedema

* Various types of rash reactions such as scaly, erythematous, maculo-papular and pustular have been reported

Metabolism and nutrition disorders

Hypercalcaemia

Hypercalciuria

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

Calcipotriol is a vitamin D derivative. In vitro data suggest that calcipotriol induces differentiation and suppresses proliferation of keratinocytes but with less effect on calcium metabolism. This is the proposed basis for its effect in psoriasis.

Absorption through skin appears to be low but that which reaches the systemic circulation is rapidly metabolised to inactive substances.

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 solution was applied topically for up to 24 months at doses of 3, 10 and 30 µg/kg/day (corresponding to 9, 30 and 90 µg/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 µg/kg/day, particularly in the males. The reduced survival was associated with an increased incidence of obstructive uropathy, most probably caused by treatment-related changes in the urinary composition. 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 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.

macrogol cetostearyl ether

cetostearyl alcohol

chloroallylhexaminium chloride (Dowicil 200)

disodium edetate

disodium phosphate dihydrate

glycerol 85%

liquid paraffin

white soft paraffin

sodium hydroxide

purified water

Not applicable.

Two years.

Store below 25°C.

Lacquered aluminium tube with polyethylene screw cap. Pack sizes: 60g and 120g.

No special requirements.

LEO Laboratories Limited, Cashel Road, Dublin 12.

PA 46/61/2

14^th March 1994/25^th February 2006

July 2008

Prescription only medicine