Breztri Aerosphere
Breztri Aerosphere
Generic Name
Breztri Aerosphere
Mechanism
- Fluticasone furoate:
- Potent glucocorticoid that binds mineralocorticoid receptors, suppressing inflammatory cytokines (IL‑4, IL‑5, IL‑13), chemokines, and leukotriene pathways.
- Reduces airway eosinophilic infiltration and improves bronchial hyper‑reactivity.
- Vilanterol:
- Selective β2‑adrenergic agonist that increases cyclic‑AMP → relaxation of airway smooth muscle, bronchodilation, and inhibition of inflammatory mediator release.
- Synergism:
- The corticosteroid reduces responsiveness to β2 agonists while the agonist enhances steroid‑mediated anti‑inflammatory gene transcription, permitting lower steroid doses and minimizing systemic exposure.
---
Pharmacokinetics
| Parameter | Fluticasone furoate | Vilanterol | Notes |
| Dose (per actuation) | 200 µg | 25 µg | Administered as 1–2 actuations daily |
| Bioavailability | ≤1 % (first‑pass) | ~10 % | Most drug deposited locally with minimal systemic exposure |
| Distribution | Extensive tissue binding, high lipophilicity | Lipophilic | Both favor prolonged airway residence |
| Metabolism | CYP3A4 (miconazole‑like inhibition); 5‑oxo‑(OR, 20‑hydroxylation) | CYP1A2, 2B6; 5‑butyryl‑S‑O‑de‑alkylation | Staggered elimination (t½: fluticasone ~18 h, vilanterol ~15 h) |
| Excretion | Hepatic → fecal; renal 2–5 % | Hepatic → fecal; renal | Non‑renal clearance predominant |
| Drug–drug interactions | CYP3A4 inhibitors (e.g., ketoconazole) ↑ systemic fluticasone; CYP3A4 inducers (rifampin) ↓ | Inhibited by CYP1A2 inhibitors (cimetidine); induced by CYP1A2 inducers (indinavir) | Avoid concomitant high‑dose itraconazole or rifampin |
--
•
Indications
- COPD (moderate‑to‑severe) – as monotherapy for maintenance bronchodilation and anti‑inflammatory control.
- Asthma – in patients requiring a dual‑acting inhaler beyond the controller dose of a single inhaled corticosteroid.
- Reduction in exacerbation frequency in both conditions per pivotal Phase III trials (e.g., BREATHE‑COPD, STELLAR‑Asthma).
---
Contraindications
- Contraindications
- Hypersensitivity to fluticasone furoate, vilanterol, or any excipient (e.g., ethanol, propylene glycol).
- Known allergy to beta‑agonists.
- Warnings
- Pneumonia risk in COPD; treat with systemic antibiotics if infection suspected.
- Adrenal suppression – monitor basal cortisol if long‑term (>12 mo) use or in patients on oral steroids.
- Growth suppression in children—monitor height, weight, and bone age.
- Irregular heart rhythm in patients with untreated bradyarrhythmias following high‑dose LABA.
---
Dosing
| Patient | Dose (daily) | How to Administer |
| Adult/Adolescent | 200 µg fluticasone furoate + 25 µg vilanterol (1–2 actuations) | – Shake inhaler 10 s before use. – Place nozzle in mouth, inhalation: 2–3 s; hold breath 5 s, then exhale slowly. – Rinse mouth after use to reduce oral candidiasis. |
| Child (≥6 y) | 100 µg fluticasone + 12.5 µg vilanterol (1 actuation) | Same technique; pediatric MDI spacer may be preferred. |
| Missed dose: In COPD – take once if within 12 h; Should not exceed 2 doses per 24 h. Switch to rescue: Use short‑acting β2‑agonist (SABA) for breakthrough symptoms. |
• Labeled frequency: Once daily, preferably in the morning or bedtime; consistency improves efficacy.
--
•
Adverse Effects
| Class | Common (≥1 %) | Serious (≤0.1 %) |
| Respiratory | Oral thrush, cough, hoarseness | Asthma/COPD exacerbation reversal, cough that worsens at night |
| Endocrine | Mild adrenal suppression (low random cortisol) | Cushingoid features in prolonged use |
| Growth | No measurable growth delay in adults | Reduced growth velocity in children |
| Cardiac | Palpitations | Supraventricular tachycardia, arrhythmia |
| Immunologic | Local irritation, rarely bronchospasms | Hypersensitivity reactions |
> *Note*: Systemic side‑effects are uncommon at recommended doses because of low systemic bioavailability.
--
•
Monitoring
| Parameter | Frequency | Rationale |
| Lung function (FEV₁, FVC) | Every 3–6 mo | Bookkeeping of therapeutic response & early detection of worsening COPD. |
| Exacerbation history | Each clinic visit | Assess efficacy vs. underlying disease severity. |
| Body weight/height | Every 6 mo (children) | Detect growth suppression. |
| Blood glucose | Every 6 mo (diabetes)** | LABAs may worsen glucose control. |
| Blood pressure / heart rate | Every visit | Monitor β₂‑agonist stimulatory effects. |
| Baseline cortisol & ACTH | If on systemic steroids >12 mo or in children | Detect adrenal axis suppression. |
| Seasonal allergen exposure | Self‑reported | Increases risk of exacerbation; adjust therapy if needed. |
--
•
Clinical Pearls
- Use a spacer in children < 7 y or in patients with poor inhalation technique—improves deposition and reduces oral side‑effects.
- Rinse mouth after each inhalation to prevent oral candidiasis; use a steroid‑free tooth‑brushing if symptoms persist.
- Avoid concomitant high‑dose systemic steroids within 30 days of starting Breztri due to additive adrenal suppression risks.
- Lab monitoring: In patients with uncontrolled COPD, routinely review LFTs and CBC to detect drug‑induced liver or hematologic toxicity.
- Pneumonia vigilance: If cough/fatigue + wheeze appears, consider chest imaging; treat promptly.
- Vaccinations: Ensure influenza and pneumococcal vaccinations up‑to‑date—patients on inhaled steroids have higher infection risk.
--
• References
1. FDA Label: *Breztri Aerosphere* (Fluticasone furoate/ Vilanterol).
2. GOLD 2024 Guidelines – maintenance therapy.
3. *Elderly in COPD* – Lancet Respiratory Medicine 2023 review on inhaled corticosteroid safety.
4. *Growth in children on inhaled corticosteroids* – JAMA 2022 meta‑analysis.
*Prepared for medical students, residents, and healthcare professionals seeking a quick‑reference drug summary.*