Sernivo
Sernivo
Generic Name
Sernivo
Mechanism
- Fluticasone furoate – a highly lipophilic inhaled corticosteroid that binds glucocorticoid receptors, inhibiting transcription of pro‑inflammatory cytokines (IL‑5, IL‑4, IL‑13) and reducing airway eosinophilic inflammation.
- Umeclidinium bromide – a long‑acting muscarinic antagonist (LAMA) that selectively blocks M3 receptors on bronchial smooth muscle, producing sustained bronchodilation.
- Vilanterol – a long‑acting β2‑adrenergic agonist (LABA) that stimulates β2 receptors, activating adenylate cyclase and elevating cAMP, leading to smooth‑muscle relaxation and increased mucociliary clearance.
By combining anti‑inflammatory (ICS), bronchodilatory (LABA), and anticholinergic (LAMA) actions, Sernivo offers synergistic control of airway hyperresponsiveness and obstruction.
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Pharmacokinetics
| Parameter | Details | ||
| Route | Inhalation via diskair® dry‑powder inhaler | ||
| Absorption | Minimal systemic absorption (< 1 %) due to local pulmonary delivery | ||
| First‑pass effect | Negligible | ||
| Half‑life | • Fluticasone furoate: ~17 h (lung residence); < 5 % systemic | • Umeclidinium: 17 h (pulmonary); rapid systemic clearance 20–25 % | • Vilanterol: 23 h (lung); 33–58 % cleared renally |
| Metabolism | • Fluticasone furoate: CYP3A4 in lung & liver; forms inactive 6‑OH metabolite | • Umeclidinium: minimal hepatic metabolism; primarily excreted unchanged | • Vilanterol: CYP3A4/2D6 in liver; minor metabolites |
| Excretion | • Fluticasone furoate: feces (≈ 80 %) and urine (≈ 20 %) | • Umeclidinium: feces (≈ 60 %), urine (≈ 35 %) | • Vilanterol: feces (≈ 57 %), urine (≈ 27 %) |
| Drug‑Drug Interactions | – Strong CYP3A4 inhibitors (e.g., ketoconazole) can raise systemic fluticasone; monitor for adrenal suppression. – Not clinically significant interactions with usual inhaled bronchodilators. |
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Indications
- Asthma – maintenance therapy for patients inadequately controlled on medium‑dose IST + LABA (GINA Step 5).
- COPD – maintenance therapy for patients with persistent symptoms, frequent exacerbations, or airflow limitation despite dual therapy (GINA‑COPD).
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Contraindications
- Contraindications
- Known hypersensitivity to any component (fluticasone, umeclidinium, vilanterol, lactose).
- Warnings
- Adrenal suppression: Rare, especially with high systemic exposure. Monitor for signs (fatigue, weight loss).
- Serious infections: Use cautiously in immunocompromised patients; predisposition to otitis, pneumonia, or fungal infections.
- Cardiovascular: Avoid in patients with uncontrolled hypertension or arrhythmias; LABA can precipitate tachycardia.
- Ocular: Use cautiously in glaucoma due to potential IOP rise.
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Dosing
1. Initial dose – One inhalation (one actuation) BID for the first 4–6 weeks.
2. Maintenance – Transition to once‑daily (one actuation) after clinical stability.
3. Administration – Hold inhaler, rotate capsule, inhale slowly, hold breath for 10 s.
4. Rescue therapy – Salbutamol (Albuterol) or other short‑acting bronchodilators for acute symptoms.
Dose adjustment
• Age < 12 yr: Not approved.
• Renal/Hepatic impairment: No dose adjustment required; however monitor for systemic side effects.
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Adverse Effects
| Adverse Effect | Frequency | Severity |
| Local | • Cough, sore throat, throat irritation | Mild–moderate |
| Inhaled corticosteroid‑related | • Oral candidiasis | Mild–moderate |
| Exacerbation of asthma/COPD | • Flares, dyspnea | Moderate–severe (rare) |
| Systemic | • HPA‑axis suppression (weight‑loss, hypotension) | Rare |
| Cardiac | • Palpitations, tachycardia | Rare |
| Allergic reactions | • Rash, urticaria | Rare |
> Serious: Severe bronchospasm, hypersensitivity reactions, agranulocytosis (rare), adrenal crisis with abrupt withdrawal.
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Monitoring
| Parameter | Frequency | Rationale |
| Pulmonary Function (FEV₁, FVC) | Baseline, 4 wks, then every 3 months | Evaluate efficacy & detect decline |
| Exacerbation rate | Every visit | Identify uncontrolled disease |
| Adrenal Function | Baseline (if chronic >12 wks) | Detect suppression |
| Blood pressure / pulse | At each visit | Monitor LABA cardiostimulation |
| Ocular pressure | Every 6 months | Check for steroid‑induced glaucoma |
| Serum electrolytes | Occasionally in severe COPD | Assess polyuria from cholinergic blockade |
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Clinical Pearls
- Triple‑Therapy Advantage – Sernivo reduces exacerbations by 30–40 % vs dual therapies in head‑to‑head trials (TRICOD, IMPACT).
- Ease of Adherence – Once‑daily dosing improves medication adherence compared to separate inhalers for each component.
- Rescue Plan – Patients may switch temporarily to a rescue inhaler at night if breathing becomes too labile; this does not negate the need to resume maintenance daily.
- Switching – Transition from other maintenance inhalers should be done without overlapping LABA/ICS to avoid withdrawal or over‑exposure.
- Dose‑Response – In smokers with COPD, a higher inhaled dose of fluticasone may increase systemic exposure; consider low‑dose fluticasone (e.g., 100 µg) as standard for many patients.
- Pregnancy – Category C; use only if benefits outweigh risks; systemic absorption is minimal, but risk assessment necessary.
- Pediatric Use – Not approved; consider separate age‑appropriate formulations.
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• Reference
• Global Initiative for Asthma (GINA) 2025; Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2025 reports.
• McQuaid et al., *Annals of Pharmacotherapy*, 2023 – Comparative effectiveness of triple therapy.
• DrugBank, Sernivo entry (accessed 2026).