Introduction
Nucala (mepolizumab) is a humanized monoclonal antibody biologic medication developed by GlaxoSmithKline. It represents a targeted therapeutic approach for patients with specific eosinophil-driven inflammatory conditions. Approved by the FDA in 2015, Nucala has revolutionized treatment for severe eosinophilic asthma and other eosinophil-associated disorders by specifically targeting interleukin-5 (IL-5), a key cytokine in eosinophil development and activation.
Mechanism of Action
Nucala exerts its therapeutic effect through precise immunomodulation. It binds specifically to human interleukin-5 (IL-5) with high affinity, preventing IL-5 from binding to its receptor on the surface of eosinophils. This interaction inhibits IL-5 signaling, which subsequently reduces eosinophil production, differentiation, recruitment, and survival. By targeting this specific pathway, Nucala effectively reduces eosinophilic inflammation without broadly suppressing the immune system, distinguishing it from conventional immunosuppressive therapies.
Indications
Nucala is FDA-approved for:
- Severe eosinophilic asthma in patients aged 6 years and older as an add-on maintenance treatment
- Chronic rhinosinusitis with nasal polyps in adults as an add-on maintenance treatment
- Hypereosinophilic syndrome (HES) for 6 months or longer in patients aged 12 years and older
- Eosinophilic granulomatosis with polyangiitis (EGPA) in adults
Dosage and Administration
Standard dosing:- 100 mg administered subcutaneously every 4 weeks
- For HES and EGPA: 300 mg administered as three separate 100 mg subcutaneous injections every 4 weeks
- Administer by healthcare professional or properly trained patient/caregiver
- Rotate injection sites (thigh, abdomen, or upper arm)
- Allow refrigerated medication to reach room temperature for 30 minutes before injection
- Do not shake the solution
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Pediatrics: Safety established for children ≥6 years (weight-based dosing not required)
- Geriatrics: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Bioavailability approximately 80% following subcutaneous administration Distribution: Volume of distribution ~5.6 L; limited tissue distribution due to large molecular size Metabolism: Degraded via proteolytic enzymes throughout the body; no hepatic cytochrome P450 involvement Elimination: Half-life ~20 days; clearance ~0.28 L/day Steady-state: Achieved after approximately 16 weeks of regular dosingContraindications
- History of hypersensitivity to mepolizumab or any component of the formulation
- Acute asthma exacerbations or acute bronchospasm (not for rescue treatment)
Warnings and Precautions
Hypersensitivity reactions: Anaphylaxis has been reported; observe patients after administration Acute asthma exacerbations: Not for treatment of acute symptoms; maintain standard rescue medications Parasitic infections: May reduce eosinophil response to helminth infections; treat pre-existing infections before initiation Corticosteroid reduction: Reduce systemic corticosteroids gradually under medical supervision Vaccinations: Live vaccines should be administered prior to initiation when possible Pregnancy: Limited data available; use only if potential benefit justifies potential riskDrug Interactions
No clinically significant pharmacokinetic interactions with:- CYP450 substrates, inhibitors, or inducers
- Common asthma medications (inhaled corticosteroids, bronchodilators)
- Theophylline, warfarin, or oral contraceptives
- Other immunosuppressive agents (increased infection risk)
- Live vaccines (reduced efficacy)
Adverse Effects
Common adverse reactions (≥5%):- Injection site reactions (pain, erythema, swelling, itching)
- Headache (18%)
- Back pain (8%)
- Fatigue (7%)
- Urinary tract infection (6%)
- Hypersensitivity reactions (1%)
- Herpes zoster infections (increased risk)
- Cardiovascular events (rare)
Monitoring Parameters
Baseline assessment:- Absolute eosinophil count
- Asthma control assessment (ACT score, spirometry)
- Parasitic infection screening
- Vaccination status
- Asthma symptoms and control every 3-6 months
- Eosinophil count (to assess therapeutic response)
- Injection site reactions
- Signs of hypersensitivity
- Infection surveillance
- Corticosteroid reduction progress (if applicable)
- Reduction in exacerbation frequency
- Improvement in lung function
- Quality of life measures
- Reduction in oral corticosteroid requirements
Patient Education
Key points for patients:- Nucala is not a rescue medication; continue all prescribed asthma medications
- Learn proper injection technique if self-administering
- Report any signs of allergic reaction (rash, swelling, difficulty breathing)
- Inform healthcare providers about all medications being taken
- Keep scheduled appointments for monitoring
- Report new or worsening symptoms promptly
- Do not stop corticosteroids without medical guidance
- Inform healthcare providers about travel to areas with parasitic infections
- Maintain good injection site rotation practices
- Store medication properly (refrigerated, protected from light)
References
1. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-1207. 2. FDA Prescribing Information: Nucala (mepolizumab). Revised 2021. 3. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189-1197. 4. Castro M, Mathur S, Hargreave F, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2011;364(11):985-993. 5. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376(20):1921-1932. 6. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of mepolizumab in severe asthma: 5-year results. J Allergy Clin Immunol. 2020;146(5):1017-1026.
This monograph is intended for educational purposes only and should not replace professional medical advice. Healthcare providers should consult current prescribing information and clinical guidelines.