Mepolizumab

• Severe Eosinophilic Asthma
• Eosinophilic Granulomatosis with Polyangiitis
• Hypereosinophilic Syndrome
• Chronic Rhinosinusitis with Nasal Polyps

Mepolizumab is a humanized monoclonal antibody that targets interleukin-5 (IL-5), a key cytokine in eosinophil biology. It is used to treat several eosinophilic conditions, including severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome.

Mechanism of Action

Mepolizumab binds to IL-5 with high affinity and specificity, preventing it from binding to IL-5 receptors on eosinophil surfaces. IL-5 is essential for eosinophil growth, differentiation, recruitment, activation, and survival. By blocking IL-5 signaling, mepolizumab:

• Reduces blood eosinophil counts
• Decreases eosinophilic airway inflammation
• Reduces eosinophil accumulation in tissues

This targeted approach addresses the underlying eosinophilic inflammation rather than just suppressing symptoms.

Available Formulations

• Lyophilized powder for reconstitution: 100 mg vial for subcutaneous injection (healthcare setting)
• Prefilled autoinjector (Nucala): 100 mg/mL for subcutaneous self-injection
• Prefilled syringe: 100 mg/mL for subcutaneous injection

Medical Uses

FDA-Approved Indications:

• Severe eosinophilic asthma in patients 6 years and older (add-on maintenance therapy)
• Eosinophilic granulomatosis with polyangiitis (EGPA) in adults
• Hypereosinophilic syndrome (HES) for 12 years and older
• Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults (add-on maintenance therapy)

Mepolizumab is particularly effective in reducing asthma exacerbations and allowing corticosteroid dose reduction.

Dosing Guidelines

Severe Eosinophilic Asthma:

• Adults and adolescents (≥12 years): 100 mg subcutaneously every 4 weeks
• Children 6-11 years: 40 mg subcutaneously every 4 weeks

EGPA:

• 300 mg subcutaneously every 4 weeks (given as three 100 mg injections)

Hypereosinophilic Syndrome:

• 300 mg subcutaneously every 4 weeks

CRSwNP:

• 100 mg subcutaneously every 4 weeks

Important Safety Information

Contraindications:

• History of hypersensitivity to mepolizumab or excipients

Warnings and Precautions:

• Hypersensitivity reactions (anaphylaxis, angioedema, bronchospasm, urticaria, rash)
• Do not use for acute bronchospasm or status asthmaticus
• Herpes zoster infections (consider vaccination before starting)
• Do not abruptly discontinue corticosteroids when starting mepolizumab

Parasitic Infections: Eosinophils may be involved in immune response to parasitic infections. Treat pre-existing helminth infections before therapy. If patients become infected during treatment and do not respond to anti-helminth therapy, consider temporary discontinuation.

Drug Interactions

No formal drug interaction studies have been conducted. Mepolizumab is not metabolized by cytochrome P450 enzymes, so interactions with small-molecule drugs are unlikely.

Special Populations

• Pregnancy: Limited human data; use only if benefit outweighs risk
• Lactation: Unknown if excreted in breast milk
• Pediatric: Approved for asthma in children ≥6 years; HES in ≥12 years
• Elderly: No dose adjustment required