Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of safety profile
Approximately 10% of patients can be expected to experience adverse skin reactions. Treatment-related adverse reactions typically associated with use of Epiduo Forte 0.3%/2.5% gel include mild to moderate application site reactions, such as skin irritation mainly characterized by scaling, dryness, erythema, and burning/stinging. Recommendation is to use moisturiser, temporarily reduce the application frequency to every other day, or temporarily discontinue its use until once daily schedule can be resumed.
These reactions usually occur early in the treatment, and tend to gradually lessen over time.
Tabulated summary of adverse reactions
The adverse reactions are classified by System Organ Class and frequency, using the following convention: 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) and were reported with Epiduo Forte 0.3%/2.5% gel in vehicle-controlled Phase 3 clinical study (see Table 1).

Table 1: Adverse reactions

System Organ Class                       Frequency                                      Adverse Reactions Uncommon                                       Erythema of eyelid
Eye disorders
Not known*                                     Eyelid oedema


Immune system                            Not known*                                     Anaphylactic reaction 

Nervous system disorders                 Uncommon                                       Paresthesia (tingling at application site) 

Respiratory, thoracic and mediastinal
Not known*                                     Throat tightness, dyspnea disorders

Skin and subcutaneous tissue disorders Common
Atopic dermatitis, eczema, skin burning sensation, skin irritation

Uncommon                                        Dry skin, pruritus, rash 
Not known*
Allergic contact dermatitis, swelling face, pain of skin (stinging pain) and blisters (vesicles),
skin discolouration, (hyperpigmentation or hypopigmentation), urticaria, application site burn **

*Post-marketing surveillance data reported since the global launch of Epiduo 0.1%/2.5% gel, from a population of unknown size **Most of the cases of “application site burn” were superficial burns but cases with second degree burn or severe burn reactions have been reported.


Skin-related adverse events were more frequent with Epiduo Forte 0.3%/2.5% gel than Epiduo gel (Adapalene 0.1% / Benzoyl peroxide 2.5%) as compared to vehicle. In the pivotal study (see section 5.1), 9.2% of subjects in the combined population treated with Epiduo Forte 0.3%/2.5% gel had skin-related adverse events and 3.7% in the population treated with Epiduo gel compared to Vehicle Gel group (2.9%).


If skin irritation appears after application of Epiduo Forte, the intensity is generally mild or moderate, with local tolerability signs and symptoms (erythema, dryness, scaling, burning and pain of skin (stinging pain) peaking during the first week and then subsiding spontaneously.

In addition to some of the above, other adverse drug reactions were reported with Epiduo gel (Adapalene 0.1% / Benzoyl peroxide 2.5%), the previously approved fixed combination of adapalene and benzoyl peroxide: - Clinical trials:
Other adverse drug reactions reported in clinical trials with Epiduo gel are irritative contact dermatitis (common) and sunburn (uncommon).

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/