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 reaction during treatment is pruritus.

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
Immune system disorders
Rare ≥1/10,000 to <1/1,000       Hypersensitivity
Eye disorders
Uncommon ≥1/1,000 to <1/100 Eye irritation
Not known                        Vision, blurred**
Skin and subcutaneous tissue disorders
Common ≥1/100 to < 1/10          Pruritus
Uncommon ≥1/1,000 to <1/100 Exacerbation of psoriasis
Dermatitis
Erythema
Rash***
Acne
Skin burning sensation
Skin irritation
Dry skin
Rare ≥1/10,000 to <1/1,000         Skin striae
Skin exfoliation
Not known                          Hair colour changes****
General disorders and administration site conditions
Uncommon ≥1/1,000 to <1/100 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.
**See section 4.4.
***Various types of rash reactions such as rash erythematous and rash pustular have been reported.
****Transient discolouration of the hair at scalp application site, to a yellowish colour in white or gray hair, has been reported.
*****Application site burning is included in application site pain.

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).

Paediatric population
No clinically relevant differences between the safety profiles in adult and adolescent populations have been observed.
A total of 216 adolescent subjects were treated in three open label clinical trials.
See section 5.1 for further details regarding the trials.

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