Adverse reactions : תופעות לוואי

4.8    Undesirable effects
Summary of the safety profile

Severe eosinophilic asthma
In placebo-controlled studies in subjects with severe refractory eosinophilic asthma, the most commonly reported adverse reactions during treatment were headache (20%), injection site reactions (8%) and back pain (6%).

CRSwNP

In a placebo-controlled study in patients with CRSwNP, the most commonly reported adverse reactions during treatment were headache (18%) and back pain (7%).

EGPA

In a placebo-controlled study in patients with EGPA, the most commonly reported adverse reactions during treatment were headache (32%), injection site reactions (15%) and back pain (13%). Systemic allergic/hypersensitivity reactions were reported by 4% of EGPA patients.


HES
In a placebo-controlled study in patients with HES, the most commonly reported adverse reactions during treatment were headache (13%), urinary tract infection (9%), injection site reactions and pyrexia (7% each).

Tabulated list of adverse reactions

The table below presents the adverse reactions from placebo-controlled severe eosinophilic asthma studies from patients receiving mepolizumab 100 mg subcutaneously (SC) (n= 263), from a randomised, double-blind placebo-controlled 52-week study in patients with CRSwNP receiving mepolizumab 100 mg SC (n=206), in patients with EGPA receiving mepolizumab 300 mg SC (n=68), in a double-blind placebo-controlled 32-week study in patients with HES receiving mepolizumab 300 mg SC (n=54), and from spontaneous post-marketing reports. Safety data is also available from open- label extension studies in severe refractory eosinophilic asthma patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years).


The safety profile of mepolizumab in HES patients (n=102) enrolled in a 20-week open label extension study was similar to the safety profile of patients in the pivotal placebo-controlled study.

The frequency of adverse reactions is defined 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); and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

System Organ Class                Adverse reactions                                 Frequency Infections and infestations       Lower respiratory tract infection                 Common Urinary tract infection
Pharyngitis
System Organ Class               Adverse reactions                                Frequency Herpes zoster**                                  Uncommon
Immune system disorders          Hypersensitivity reactions (systemic             Common allergic)*
Anaphylaxis**                                    Rare
Nervous system disorders         Headache                                         Very common Respiratory, thoracic and        Nasal congestion                                 Common mediastinal disorders
Gastrointestinal disorders       Abdominal pain upper                             Common Skin and subcutaneous tissue     Eczema                                           Common disorders
Musculoskeletal and              Back pain                                        Common connective tissue disorders      Arthralgia**
General disorders and            Administration-related reactions (systemic       Common administration site conditions   non allergic)***
Local injection site reactions
Pyrexia
* Systemic reactions including hypersensitivity have been reported at an overall incidence comparable to that of placebo in the severe eosinophilic asthma studies. For examples of the associated manifestations reported and a description of the time to onset, see section 4.4.
**From spontaneous post marketing reporting.
*** The most common manifestations associated with reports of systemic non-allergic administration- related reactions from patients in the severe eosinophilic asthma studies were rash, flushing and myalgia; these manifestations were reported infrequently and in <1% of patients receiving mepolizumab 100 mg subcutaneously.

Description of selected adverse reactions

Systemic reactions, including hypersensitivity reactions, in CRSwNP
In the 52-week placebo-controlled study, systemic allergic (type I hypersensitivity) reactions were reported in 2 patients (<1%) in the group receiving mepolizumab 100 mg and in no patients in the placebo group. Other systemic reactions were reported by no patients in the group receiving mepolizumab 100 mg and in 1 patient (<1%) in the placebo group.

Systemic reactions, including hypersensitivity reactions, in EGPA

In the 52-week placebo-controlled study the percentage of patients who experienced systemic (allergic and non-allergic) reactions was 6% in the group receiving 300 mg of mepolizumab and 1% in the placebo group. Systemic allergic/hypersensitivity reactions were reported by 4% of patients in the group receiving 300 mg of mepolizumab and 1% of patients in the placebo group. Systemic non- allergic reactions (angioedema) were reported by 1 (1%) patient in the group receiving 300 mg of mepolizumab and no patients in the placebo group.

Systemic reactions, including hypersensitivity reactions, in HES

In the 32-week placebo-controlled study, 1 patient (2%) reported a systemic (other) reaction in the group receiving 300 mg of mepolizumab (multifocal skin reaction) and no patients in the placebo group.

Local injection site reactions
Severe eosinophilic asthma
In placebo-controlled studies the incidence of local injection site reactions with mepolizumab 100 mg subcutaneous and placebo was 8% and 3%, respectively. These events were all non-serious, mild to moderate in intensity and the majority resolved within a few days. Local injection site reactions occurred mainly at the start of treatment and within the first 3 injections with fewer reports on subsequent injections. The most common manifestations reported with these events included pain, erythema, swelling, itching, and burning sensation.

CRSwNP

In the placebo-controlled study, local injection site reactions (e.g., erythema, pruritus) occurred in 2% of patients receiving mepolizumab 100 mg compared with <1% in patients receiving placebo.

EGPA
In the placebo-controlled study, local injection site reactions (e.g., pain, erythema, swelling) occurred at a rate of 15% in patients receiving mepolizumab 300 mg compared with 13% in patients receiving placebo.

HES

In the placebo-controlled study, local injection site reactions (e.g., burning, itching) occurred at a rate of 7% in patients receiving mepolizumab 300 mg compared with 4% in patients receiving placebo.

Special data from clinical studies:

HES
Haemorrhage
In phase 3 placebo-controlled study 200622, a higher number of subjects reporting hemorrhages was observed for mepolizumab 300 mg SC group (10/54 patients, 19%) compared to the placebo arm, (4/54 patients, 7%).
The majority of cases were mild or moderate in intensity and resolved. Five out of 10 of the patients treated with mepolizumab had concomitant medications that could increase the risk of bleeding (including anticoagulants). No causal relationship with mepolizumab has been determined yet.

Paediatric population

Nucala is not indicated for children and adolescents under 18 years of age.
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
Additionally, you should also report to GSK Israel (il.safety@gsk.com)