Advair Diskus
Advair Diskus
Generic Name
Advair Diskus
Mechanism
- Fluticasone propionate: As a glucocorticoid, it binds intracellular glucocorticoid receptors, translocates to the nucleus, and modulates gene transcription. Resulting actions include:
- Downregulation of pro‑inflammatory cytokines (IL‑4, IL‑5, IL‑13, TNF‑α).
- Inhibition of eosinophil recruitment and activation.
- Suppression of mast cell degranulation.
- Reduction in airway hyperresponsiveness and mucous production.
- Salmeterol: A selective β2‑adrenergic receptor agonist that activates adenylate cyclase → ↑cAMP → smooth‑muscle relaxation, bronchodilation, and attenuation of bronchial edema.
- The combination provides dual anti‑inflammatory and bronchodilatory effects, enabling better maintenance control of asthma and chronic obstructive pulmonary disease (COPD) compared with either agent alone.
Pharmacokinetics
| Parameter | Fluticasone (ID) | Salmeterol (ID) |
| Absorption | Pulmonary deposition > 80 % of delivered dose; minimal systemic absorption. | Pulmonary deposition > 80 %; systemic exposure negligible. |
| Distribution | Highly lipophilic; extensive protein binding (~99 %). | High protein binding; extensive peripheral tissue binding. |
| Metabolism | Hepatic CYP3A4 → 4‑OH‑fluticasone; extensive first‑pass metabolism in the lung. | Hepatic CYP3A/1A2 → inactive metabolites. |
| Elimination | Biliary excretion; half‑life in lung ~2 h, systemic ~8 h. | Renal excretion; half‑life in lung ~3 h, systemic ~23 h. |
| Steady‑state | Achieved after ~2 weeks. | Achieved after ~10 days. |
> Key point: Systemic bioavailability is < 3 % for each component, limiting systemic side effects when used as prescribed.
Indications
- Asthma (maintenance): Adults and adolescents ≥ 12 yr for long‑term control; also used pre‑exercise prophylaxis in appropriate patients.
- Chronic Obstructive Pulmonary Disease (COPD): Adults ≥ 18 yr with persistent airflow limitation; used as a maintenance therapy to improve lung function and reduce exacerbations.
> *Note*: Advair Diskus is *not* indicated for acute bronchospasm or rescue therapy.
Contraindications
- Contraindications
- Known hypersensitivity to fluticasone, salmeterol, or any excipient (e.g., lactose).
- Severe uncontrolled asthma requiring high‑dose rescue β2‑agonist use.
- Warnings
- Respiratory infections: Use with caution in patients with active asthma exacerbation, COPD flare‑up, or serious respiratory infection.
- Immunosuppression: Long‑term use may impair local immune defense; monitor for oral candidiasis and pneumonitis.
- Ocular effects: Local side‑effects include eye irritation, cataract, and increased intra‑ocular pressure.
- Cardiovascular: Use cautiously in patients with uncontrolled hypertension, arrhythmias, or ischemic heart disease.
- Drug interactions
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) ↑ systemic fluticasone; monitor for Cushingoid features.
- CYP3A4 inducers (e.g., rifampicin) ↓ effectiveness of both agents.
Dosing
| Indication | Powder Strength | Adult Dose (2×5 acts/day) | Pediatric Dose (12‑17 yr) |
| Asthma | 100/50 µg | 2 acts twice daily | 2 acts twice daily (reduced at 1 yr). |
| Asthma | 250/50 µg | 4 acts twice daily | 2 acts twice daily (titrated). |
| Asthma | 500/50 µg | 4 acts twice daily | 2 acts twice daily. |
| COPD | 250/50 µg | 2 acts twice daily | – |
| COPD | 500/50 µg | 2 acts twice daily | – |
• Technique: Prime the Diskus before first use and after every 4 days of use. Inhale a puff, exhale, hold breath for 10 sec, then rest 5–10 sec before next actuation.
• Switch to maintenance: Starting with the lowest effective dose; step‑up or down per GINA/GINA/ATS guidelines.
• Discontinuation: Gradual taper if needed to avoid withdrawal or rebound bronchospasm.
Monitoring
- Pulmonary function: FEV1 in asthma/COPD at baseline, 4–6 weeks, then every 4–6 months.
- Blood pressure & heart rate weekly initially in early treatment.
- Body weight & waist circumference every 3 months; assess for Cushingoid features.
- Blood glucose in diabetics every 3–6 months.
- Bone mineral density after ≥3 years of therapy or if additional systemic steroids are used.
- Oral examination for candidiasis at each visit.
- Adrenal function: 8 AM serum cortisol or midnight urinary cortisol if adrenal suppression suspected.
Clinical Pearls
- Single Inhaler Advantage: Reduces separate rescue device burden, improves adherence, and simplifies titration in both asthma and COPD.
- Prime‑the‑Device: Essential to avoid particle loss; left unattended devices can lose up to 30 % of the dose.
- Use with Nebulizer?: Not recommended—fluticasone degrades rapidly in nebulizers.
- Salmeterol Side‑Effects: Provoke tachycardia and tremor in susceptible individuals; advise patients to monitor pulse if symptoms arise.
- COPD–Asthma Overlap: Patients with the overlap syndrome benefit most from dual therapy; consider starting at 250/50 µg, then escalating.
- Pre‑Exercise: A single puff 5–10 min before exercise can blunt exercise‑induced bronchoconstriction—use only in patients with intermittent exercise‑induced symptoms.
- Adrenal Suppression Mitigation: Short courses of systemic steroids during exacerbations should be avoided; instead use higher inhaled dose for a limited period.
- Pediatric Use: For children 12–17 yr, dosing starts low (2 acts + 2 acts) and escalates cautiously; never exceed 4 acts per day unless titrated by a pulmonologist.
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• Key Takeaway: *Advair Diskus*, combining fluticasone propionate and salmeterol, offers a synergistic anti‑inflammatory and bronchodilatory effect with low systemic exposure, making it a cornerstone for maintenance therapy in both asthma and COPD when used correctly and monitored diligently.