Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies including post-authorisation safety studies and spontaneous reporting.
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. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

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)
Infections and infestations
Uncommon ≥1/1,000 to <1/100                       Skin infection* Folliculitis
Rare (≥1/10,000 to <1/1,000)                      Furuncle
Immune system disorders
Rare (≥1/10,000 to <1/1,000)                      Hypersensitivity Metabolism and nutrition disorders
Rare (≥1/10,000 to <1/1,000)                      Hypercalcaemia
Eye disorders
Not known                                         Vision, blurred**** Skin and subcutaneous tissue disorders
Common (≥1/100 to <1/10)                          Skin exfoliation Pruritus
Uncommon (≥1/1,000 to <1/100)                     Skin atrophy
Exacerbation of psoriasis
Dermatitis
Erythema
Rash**
Purpura or ecchymosis
Skin burning sensation
Skin irritation
Rare (≥1/10,000 to <1/1,000)                      Pustular psoriasis Skin striae
Photosensitivity reaction
Acne
Dry skin

General disorders and administration site conditions
Uncommon (≥1/1,000 to <1/100)                 Application site pigmentation changes Application site pain***
Rare (≥1/10,000 to <1/1,000)                  Rebound effect

*Skin infections including bacterial, fungal and viral skin infections have been reported.
**Various types of rash reactions such as rash exfoliative and rash pustular have been reported.
***Application site burning is included in application site pain.
****See section 4.4.

Paediatric population
In an uncontrolled open study, 33 adolescents aged 12-17 years with psoriasis vulgaris were treated with Daivobet ointment for 4 weeks to a maximum of 56 g per week. No new adverse events were observed and no concerns regarding systemic corticosteroid effect were identified. The size of this study does however not allow firm conclusions regarding the safety profile of Daivobet ointment in children and adolescents.

The following adverse reactions are considered to be related to the pharmacological classes of calcipotriol and betamethasone, respectively:

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 very rare cases of angioedema and facial oedema.
Systemic effects after topical use may appear very rarely 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 rare 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 medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il