Ngenla
Ngenla
Generic Name
Ngenla
Mechanism
- Selective IL‑5 blockade: binds circulating IL‑5 with high affinity, preventing interaction with the IL‑5 receptor (IL‑5Rα) on eosinophils and basophils.
- Reduced eosinophil maturation and survival: decreases peripheral eosinophil counts, limits tissue eosinophilic inflammation, and diminishes eosinophil‑mediated airway remodeling.
- Downstream effects: attenuates release of eosinophil granule proteins (MBP, ECP) and lipid mediators that drive bronchial hyperresponsiveness and exacerbations.
Pharmacokinetics
- Route: Subcutaneous injection; 100 mg in 0.5 mL or 300 mg in 2 mL, depending on indication.
- Absorption: ~90 % bioavailability; peak concentration (Cmax) achieved ~1–2 weeks post‑dose.
- Distribution: Vol. of distribution ≈ 12–15 L, limited to extracellular fluid.
- Metabolism: Proteolytic cleavage into peptides; minimal cytochrome P450 interaction.
- Elimination: Non‑saturable, linear elimination; terminal half‑life ≈ 21–24 days; steady state reached after ~4–6 months.
- Renal/ Hepatic: No dose adjustment required for mild‑to‑moderate renal or hepatic impairment.
Indications
- Severe eosinophilic asthma (≥ 2 exacerbations/yr despite high‑dose inhaled corticosteroids + LABA/GLPRA) – 100 mg SC every 4 weeks.
- Eosinophilic granulomatosis with polyangiitis (EGPA) – 300 mg SC every 4 weeks (preferred in patients with eosinophilic serum counts > 300/µL).
- Adjunct to standard therapy: Helps reduce oral corticosteroid dose or achieve steroid‑free remission.
Contraindications
- Contraindications:
- Known hypersensitivity to *mepolizumab* or any excipients (e.g., polysorbate 80).
- Active systemic infection requiring antibiotics.
- Warnings:
- Allergic reactions: anaphylaxis risk; monitor for rash, pruritus, shortness of breath.
- Impaired immune function: infections (e.g., urinary tract infections) can be more severe in chronic users.
- Vaccinations: live vaccines contraindicated; inactivated vaccines may need to be timely coordinated.
Dosing
| Indication | Dose | Schedule | Administration | Notes |
| Severe eosinophilic asthma | 100 mg | SC q4 weeks | 0.5 mL IM/SC | Initiate at 4 weeks; adjust clinical response. |
| EGPA | 300 mg | SC q4 weeks | 2 mL IM/SC | Use only if serum eosinophils > 300/µL or uncontrolled disease. |
• Pre‑injection assessment: Verify no acute infections, confirm dosage.
• Post‑dose monitoring: Observation 15–30 min for hypersensitivity reactions.
• Storage: 2 – 8 °C; may be frozen ≤ −25 °C if stored > 28 days.
• Reconstitution: 3 mL sterile water for injection → 3 mL final solution; use immediately or store at 2 – 8 °C for 7 days.
Adverse Effects
| Category | Most Common | Serious / Rare |
| Injection‑site reactions | erythema, swelling, pain | cellulitis, abscess |
| Upper respiratory | nasopharyngitis, sinusitis | severe asthma exacerbation |
| Headache | mild to moderate | |
| Hematologic | neutropenia (rare) | agranulocytosis |
| Immune‑mediated | arthralgia, myalgia | systemic hypersensitivity, anaphylaxis |
| Others | fatigue, dizziness | hepatic enzyme elevation (rare) |
• Serious infections: persistent cough with fever, chest pain → assess for bacterial pneumonia.
• Worsening asthma: paradoxical exacerbation in 1–2 % of patients; promptly evaluate inhaler technique and adherence.
Monitoring
- Baseline: CBC with differential, liver function tests, serum IgE.
- Periodic:
- CBC (every 3 months) to detect eosinophil count and neutropenia.
- Pulmonary function tests (FEV1) every 3–6 months or after exacerbation.
- Blood pressure & ECG if comorbid cardiovascular disease.
- Safety: Review for signs of infection, injection‑site complications, or anaphylaxis after each visit.
Clinical Pearls
- Eosinophil count as target: Aim for > 150/µL in asthma before tapering steroids; a rapid decline > 75 % predicts steroid‑free remission.
- Octogenarians & comorbidities: No special dose adjustment, but monitor for infections due to immunosuppression.
- Drug interactions: Minimal; safe with inhaled corticosteroids, LABAs, leukotriene modifiers; avoid concurrent monoclonal antibodies targeting IL‑5 (duplicate therapy).
- Patient education: Emphasize: “Subcutaneous injection frequency is every 4 weeks, not daily.” Discuss potential for mild injection-site soreness but no need for pre‑medication.
- In pregnancy: Limited data; weigh benefits versus unknown risks; may be used in severe asthma when other treatments fail.
- Serious adverse events: If anaphylaxis occurs, treat with epinephrine and discontinue therapy.
- Transitioning: Switching from oral steroids to *mepolizumab* should involve a step‑down protocol; standard to start Ngenla at baseline, reduce oral steroids by 5 mg prednisone equivalent per month if tolerated.
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• Key terms: *Ngenla*, *mepolizumab*, IL‑5, eosinophilic asthma, EGPA, monoclonal antibody, subcutaneous injection, steroid‑sparing. Tailor this card for quick reference during rotations, exams, or bedside teaching.