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.
The most frequently reported adverse reactions during treatment are application site reactions.
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                                    Folliculitis 
Immune system disorders

Uncommon ≥1/1,000 to <1/100                                    Hypersensitivity 
Metabolism and nutrition disorders

Uncommon ≥1/1,000 to <1/100                                    Hypercalcaemia* 
Eye disorders

Not known                                                      Vision, blurred** 
Skin and subcutaneous tissue disorders

Uncommon ≥1/1,000 to <1/100                                    Skin hypopigmentation 
Not known                                                      Hair colour changes*** 
General disorders and administration site conditions

Uncommon ≥1/1,000 to <1/100                                    Rebound effect Application site pruritus
Application site irritation
Application site pain****
Not known                                                            Application site erythema***** 
*Mild hypercalcaemia has been observed.
**See section 4.4.
***Transient discolouration of the hair at scalp application site, to a yellowish colour in white or grey hair, has been reported for calcipotriol and betamethasone combination products.
****Application site burning is included in application site pain.
*****Based on post-marketing experience.
Paediatric population
No clinically relevant differences between the safety profiles in adult and adolescent populations have been observed. A total of 106 adolescent subjects were treated in one open-label clinical trial. See section 5.1 for further details regarding this trial.
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, 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, impaired glycaemic 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 onto large skin 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