NUCALA

Nucala should be prescribed by physicians experienced in the diagnosis and treatment of severe refractory eosinophilic asthma. Posology Children aged 6 to 11 years old The recommended dose of mepolizumab is 40 mg administered subcutaneously once every 4 weeks.

Nucala is intended for long-term treatment. The need for continued therapy should be considered at least on an annual basis as determined by physician assessment of the patient’s disease severity and level of control of exacerbations.

2). Paediatric population Children aged 6 to 11 years old Nucala 100 mg powder for solution for injection and 40 mg solution for injection in pre-filled syringe are appropriate for administration to this population. Nucala 100 mg solution for injection in pre-filled pen and 100 mg solution for injection in pre-filled syringe are not indicated for administration to this population.

Children less than 6 years old The safety and efficacy of mepolizumab in children less than 6 years old have not yet been established. No data are available. Method of administration The pre-filled syringe should be used for subcutaneous injection only.

Nucala must be administered by a healthcare professional or a caregiver. It may be administered by a caregiver if a healthcare professional determines that it is appropriate, and the caregiver is trained in injection techniques. The recommended injection sites are the upper arm, abdomen or thigh.

Comprehensive instructions for subcutaneous administration of Nucala in a pre-filled syringe are provided in the instructions for use in the package leaflet.

Summary of the safety profile Severe eosinophilic asthma In placebo-controlled studies in adult and adolescent patients 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.

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 Urinary tract infection Pharyngitis Herpes zoster** Common Uncommon Immune system disorders Hypersensitivity reactions (systemic allergic)* Anaphylaxis** Common Rare System Organ Class Adverse reactions Frequency Nervous system disorders Headache Very common Respiratory, thoracic and mediastinal disorders Nasal congestion Common Gastrointestinal disorders Abdominal pain upper Common Skin and subcutaneous tissue disorders Eczema Common Musculoskeletal and connective tissue disorders Back pain Arthralgia** Common General disorders and administration site conditions Administration-related reactions (systemic non allergic)*** Local injection site reactions Pyrexia Common * Systemic reactions including hypersensitivity have been reported at an overall incidence comparable to that of placebo in the severe eosinophilic asthma studies.

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.

, erythema, pruritus) occurred in 2% of patients receiving mepolizumab 100 mg compared with <1% in patients receiving placebo. , pain, erythema, swelling) occurred at a rate of 15% in patients receiving mepolizumab 300 mg […]

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Asthma exacerbations Mepolizumab should not be used to treat acute asthma exacerbations.

Asthma-related adverse symptoms or exacerbations may occur during treatment. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment. Corticosteroids Abrupt discontinuation of corticosteroids after initiation of mepolizumab therapy is not recommended.

Reduction in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician. g. anaphylaxis, urticaria, angioedema, rash, bronchospasm, hypotension), have occurred following administration of mepolizumab.

, typically within several days). 8). In the event of a hypersensitivity reaction, appropriate treatment as clinically indicated should be initiated. Parasitic infections Eosinophils may be involved in the immunological response to some helminth infections.

Patients with pre-existing helminth infections should be treated before starting therapy. If patients become infected whilst receiving treatment with mepolizumab and do not respond to anti-helminth treatment, temporary discontinuation of therapy should be considered.

Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose,that is to say essentially “sodium-free”.

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