Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
The most commonly reported adverse reactions with apremilast in PsA and PSOR are gastrointestinal (GI) disorders including diarrhea (15.7%) and nausea (13.9%). The other most commonly reported adverse reactions include upper respiratory tract infections (8.4%), headache (7.9%), and tension headache (7.2%) and are mostly mild to moderate in severity.

The most commonly reported adverse drug reactions with apremilast in BD are diarrhea (41.3%), nausea (19.2%), headache (14.4%), upper respiratory tract infection (11.5%), upper abdominal pain (8.7%), vomiting (8.7%) and back pain (7.7%) and are mostly mild to moderate in severity.

The gastrointestinal adverse reactions generally occurred within the first 2 weeks of treatment and usually resolved within 4 weeks.

Hypersensitivity reactions are uncommonly observed (see section 4.3).

Tabulated list of adverse reactions
The adverse reactions observed in patients treated with apremilast are listed below by system organ class (SOC) and frequency for all adverse reactions. Within each SOC and frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The adverse drug reactions were determined based on data from the apremilast clinical development program and post-marketing experience. The frequencies of adverse drug reactions are those reported in the apremilast arms of the four Phase III studies in PsA (n = 1945) or the two Phase III studies in PSOR (n=1184), and in the phase III study in BD (n=207) the highest frequency from either data pool is represented in Table 2.

Frequencies are defined as: 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); not known (cannot be estimated from the available data).

Table 2. Summary of adverse reactions in psoriatic arthritis (PsA), psoriasis (PSOR) and Behçet’s disease (BD)
System Organ Class                             Frequency           Adverse reaction Infections and infestations                    Very common         Upper respiratory tract infection a Common              Bronchitis
Nasopharyngitis*


Immune system disorders                        Uncommon            Hypersensitivity Metabolism and nutrition disorders             Common              Decreased appetite* Psychiatric disorders                          Common              Insomnia Depression
Uncommon            Suicidal ideation and behavior
Nervous system disorders                       Very common         Headache* a Common              Migraine*
Tension headache*


Respiratory, thoracic, and mediastinal         Common              Cough disorders
Gastrointestinal disorders                     Very Common         Diarrhea* Nausea*
Common              Vomiting*
Dyspepsia
Frequent bowel movements
Upper abdominal pain *
Gastroesophageal reflux disease
Uncommon            Gastrointestinal hemorrhage
Skin and subcutaneous tissue disorders         Uncommon            Rash Urticaria
Not known           Angioedema
Musculoskeletal and connective tissue          Common              Back pain* disorders
General disorders and administration site      Common              Fatigue conditions
Investigations                                 Uncommon            Weight decrease *At least one of these adverse reactions was reported as serious a
Frequency reported as common in PSA and PSOR


Description of selected adverse reactions
Psychiatric disorders
In clinical studies and post-marketing experience, uncommon cases of suicidal ideation and behavior, were reported, while completed suicide was reported post-marketing. Patients and caregivers should be instructed to notify the prescriber of any suicidal ideation (see section 4.4).

Body weight loss
Patient weight was measured routinely in clinical studies. The mean observed weight loss in PsA and PSOR patients treated for up to 52 weeks with apremilast was 1.99 kg. A total of 14.3% of patients receiving apremilast had observed weight loss between 5-10% while 5.7% of the patients receiving apremilast had observed weight loss greater than 10%. None of these patients had overt clinical consequences resulting from weight loss. A total of 0.1% of patients treated with apremilast discontinued due to adverse reaction of weight decreased. The mean observed weight loss in BD patients treated with apremilast for 52 weeks was 0.52 kg. A total of 11.8% of patients receving apremilast had observed weight loss between 5-10% while 3.8% of the patients receiving apremilast had observed weight loss greater than 10%. None of these patients had overt clinical consequences from weight loss. None of the patients discontinued the study due to adverse reaction of weight decreased.

Please see additional warning in section 4.4 for patients who are underweight at beginning of treatment.

Special populations
Elderly patients
From post-marketing experience, elderly patients ≥ 65 years of age may be at a higher risk of complications of severe diarrhea, nausea and vomiting (see section 4.4).

Patients with hepatic impairment
The safety of apremilast was not evaluated in PsA, PSOR or BD patients with hepatic impairment.

Patients with renal impairment
In the PsA, PSOR or BD clinical studies, the safety profile observed in patients with mild renal impairment was comparable to patients with normal renal function. The safety of apremilast was not evaluated in PsA, PSOR or BD patients with moderate or severe renal impairment in the clinical studies.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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/