Mepolizumab

NUCALA is an interleukin-5 (IL-5) antagonist monoclonal antibody (IgG1 kappa) indicated for: • Add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype. • Add-on maintenance treatment of adult patients aged 18 years and older with chronic rhinosinusitis with nasal polyps (CRSwNP). • Add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. • The treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). • The treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for greater than or equal to 6 months without an identifiable non-hematologic secondary cause. Limitations of use: Not for relief of acute bronchospasm or status asthmaticus.

Mepolizumab is an IL-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma, CRSwNP, COPD, EGPA, and HES. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils, however, the mechanism of mepolizumab action in asthma, CRSwNP, COPD, EGPA, and HES has not been definitively established.

• Severe asthma in patients aged 12 years and older: 100 mg administered subcutaneously once every 4 weeks. • Severe asthma in patients aged 6 to 11 years: 40 mg administered subcutaneously once every 4 weeks. • CRSwNP: 100 mg administered subcutaneously once every 4 weeks. • COPD: 100 mg administered subcutaneously once every 4 weeks. • EGPA: 300 mg administered subcutaneously once every 4 weeks. • HES: 300 mg administered subcutaneously once every 4 weeks.

NUCALA is contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation. History of hypersensitivity to mepolizumab or excipients in the formulation.

• Hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after administration of NUCALA. Discontinue NUCALA in the event of a hypersensitivity reaction. • Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate. • Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decrease corticosteroids gradually, if appropriate. • Treat patients with pre-existing helminth infections before therapy with NUCALA. If patients become infected while receiving treatment with NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until parasitic infection resolves.

The following adverse reactions are described in greater detail in other sections: • Hypersensitivity reactions • Opportunistic infections: herpes zoster Most common adverse reactions (incidence ≥5%): • Asthma: Headache, injection site reaction, back pain, and fatigue. • CRSwNP: Oropharyngeal pain and arthralgia. • COPD: Back pain, diarrhea, and cough. • EGPA and HES: Most common adverse reactions are similar to asthma.

Formal drug interaction trials have not been performed with NUCALA.

Store vials below 77°F (25°C). Do not freeze. Prior to Dispensing: Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Do not freeze. Following Dispensing: Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Do not freeze. If necessary, an unopened carton can be stored outside the refrigerator at up to 86°F (30°C) for up to 7 days. Discard if left out of the refrigerator for more than 7 days. Store in the original carton to protect from light. Keep the product in the original carton to protect from light. Do not shake. Keep the product in the original carton to protect from light until the time of use. Do not shake.