Dovobet 50 μg Ointment.

Treatment of psoriasis vulgaris.

Adults
DOVOBET should be applied to the affected area once daily. The recommended treatment period is 4 weeks. There is experience with repeated courses of DOVOBET up to 52 weeks. If it is necessary to continue or restart treatment after 4 weeks, treatment should be continued under medical review and under regular medical supervision. The maximum daily dose should not exceed 15 g, and the maximum weekly dose should not exceed 100 g. The treated area should not be more than 30 % of the body surface.

Children
There is no experience of use in children and adolescents below the age of 18 years.

Method of administration
DOVOBET ointment should be applied to the affected area. In order to achieve optimal effect, it is not recommended to take a shower or bath immediately after application of DOVOBET ointment.

• Known hypersensitivity to calcipotriol, betamethasone or to any of the excipients listed in section 6.1.
• DOVOBET is contraindicated in erythrodermic, exfoliative and pustular psoriasis.
• DOVOBET is contraindicated in patients with known disorders of calcium metabolism due to the content of calcipotriol (see section 4.4).
• Due to the content of corticosteroid, DOVOBET is contraindicated in the following conditions: viral (e.g., herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds (see section 4.4).
• DOVOBET is contraindicated in patients with severe hepatic disorders or severe renal insufficiency.
• Safe use of DOVOBET during human pregnancy and lactation has not been established. Corticosteroids have been shown to be teratogenic in animals following dermal application. As these agents are absorbed percutaneously, teratogenicity following topical application cannot be excluded. Therefore, DOVOBET should not be used during pregnancy.

Effects on endocrine system
DOVOBET ointment contains a potent group III steroid and concurrent treatment with other steroids must be avoided. Adverse reactions 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 systemic absorption.

Application under occlusive dressings should be avoided since it increases the systemic absorption of corticosteroids. Application on large areas of damaged skin, or on mucous membranes or in skin folds should be avoided since it increases the systemic absorption of corticosteroids (see section 4.8).

A borderline decrease in cortisol response to adrenocorticotropic hormone (ACTH) challenge after 4 weeks of treatment was reported in patients with both extensive scalp and extensive body psoriasis using a combination of high doses of DOVOBET gel (scalp application) and high doses of DOVOBET ointment (body application).

Visual disturbance
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for a referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Effects on calcium metabolism
Due to the calcipotriol content of DOVOBET, hypercalcaemia may occur if the maximum weekly dose (15 g) is exceeded. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the recommendations relevant to calcipotriol are followed. Treatment of more than 30 % of the body surface should be avoided (see section 4.2).

Local adverse reactions
DOVOBET contains a potent group III-steroid and concurrent treatment with other steroids on the same treatment area must be avoided. Skin of the face and genitals are very sensitive to corticosteroids. DOVOBET should not be used in these areas. The patient must be instructed in correct use of DOVOBET to avoid application and accidental transfer to the face, scalp, mouth or eyes. Hands must be washed after each application to avoid accidental transfer to these areas.

Concomitant skin infections
When lesions become secondarily infected, they should be treated with antimicrobiological therapy. However, if infection worsens, treatment with DOVOBET should be stopped (see section 4.3).

Discontinuation of treatment
When treating psoriasis with topical corticosteroids, such as contained in DOVOBET, there may be a risk of generalised pustular psoriasis or of rebound effects when discontinuing treatment. Medical supervision should therefore continue in the post-treatment period.

Long-term use
With long-term use there is an increased risk of local and systemic corticosteroid adverse reactions. The treatment should be discontinued in case of adverse reactions related to long-term use of corticosteroid (see section 4.8).

Unevaluated use
There is no experience with the use of DOVOBET in guttate psoriasis.

Concurrent treatment and UV exposure
There is limited experience for the use of this medicine on the scalp. DOVOBET ointment for body psoriasis lesions has been used in combination with DOVOBET gel for scalp psoriasis lesions, but there is limited experience of combination of DOVOBET with other topical anti-psoriatic products at the same treatment area, other anti-psoriatic medicines administered systemically or with phototherapy. During DOVOBET treatment, patients should limit or avoid excessive exposure to either natural or artificial sunlight.

No interaction studies have been performed with DOVOBET.

Safety and efficacy in pregnancy and lactation have not been established (see section 4.3)

Pregnancy
DOVOBET is contraindicated in pregnancy (see section 4.3). The potential risk for use of DOVOBET during pregnancy is uncertain.

Breastfeeding
Caution should be exercised when prescribing DOVOBET to women who are breastfeeding. The patient should also be instructed to not use DOVOBET on the breast whilst breastfeeding.

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

The most frequently reported adverse reactions during treatment are various skin reactions, like pruritus and skin exfoliation. Pustular psoriasis and hypercalcaemia have been reported. Adverse reactions are listed by MedDRA SOC and the individual adverse reactions are listed starting with the most frequently reported.

Infections and infestations
Less frequent Skin infection*, folliculitis, furuncle

Blood and lymphatic system disorders
Less frequent Ecchymosis

Immune system disorders
Less frequent Hypersensitivity

Endocrine disorders
Less frequent Hirsutism, cushings syndrome

Metabolism and nutrition disorders
Less frequent Hypercalcaemia, hypokalaemic syndrome

Nervous system disorders
Less frequent Hyperaesthesia, numbness in fingers

Eye disorders
Not known Blurred vision****, Posterior subscapular cataracts

Vascular disorders
Less frequent Hypertension

Gastrointestinal disorder
Less frequent Gastric ulcer

Skin and subcutaneous tissue disorders
Frequent Skin exfoliation, pruritus, rash**, burning sensation of the skin
Less frequent Skin atrophy, exacerbation of psoriasis, dermatitis, erythema, purpura or ecchymosis, skin irritation, pustular psoriasis, skin striae, photosensitivity reaction, acne, dry skin

Musculoskeletal and connective tissue disorders
Less frequent Protein depletion

General disorders and administration site conditions
Less frequent Application site pigmentation changes, application site pain***, rebound effect, Oedema

*Skin infections including bacterial, fungal and viral skin infections have been reported.

**Various types of rash reactions such as exfoliative rash, rash papular and rash pustular have been reported.

***Application site burning is included in application site pain.

****See section 4.4.

Paediatric population
The safety of DOVOBET ointment in children below 18 years have not been established. Calcipotriol Adverse reactions include application site reactions, pruritus, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, psoriasis aggravated, photosensitivity and hypersensitivity reactions including less frequent cases of angioedema and facial oedema. Systemic effects after topical use may appear less frequently causing hypercalcaemia or hypercalciuria, (see section 4.4).

Betamethasone (as dipropionate)
Local reactions can occur after topical use, especially during prolonged application, including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid milia. When treating psoriasis with topical corticosteroids, there may be a risk of generalised pustular psoriasis. Systemic reactions due to topical use of corticosteroids are less frequent in adults, however they can be severe. Adrenocortical suppression, cataract, infections, impact on the metabolic control of diabetes mellitus and increase of intra-ocular pressure can occur, especially after long term treatment. Systemic reactions occur more frequently when applied under occlusion (plastic, skin folds), when applied on large areas and during long term treatment (see section 4.4).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8. Additionally, suspected adverse reactions can be reported to the Holder of Certificate of Registration via [email protected].

Use above the recommended dose may cause elevated serum calcium which subsides when treatment is discontinued. The symptoms of hypercalcaemia include polyuria, constipation, muscle weakness, confusion and coma. Excessive prolonged use of topical corticosteroids, as contained in DOVOBET, may suppress the pituitary-adrenal functions, resulting in secondary adrenal insufficiency which is usually reversible. Treatment is symptomatic and supportive. In cases of toxicity due to chronic use, DOVOBET treatment must be discontinued gradually.

It has been reported that due to misuse one patient with extensive erythrodermic psoriasis treated with 240 g of DOVOBET ointment weekly (corresponding to a daily dose of approximately 34 g) for 5 months (maximum recommended dose 15 g daily) developed Cushingu2019s syndrome during treatment and then pustular psoriasis after abruptly stopping treatment.