Generic Name

Salmeterol

Mechanism

Salmeterol acts selectively on β2‑adrenergic receptors in airway smooth muscle, causing:
• *Gαs*‑mediated adenylate cyclase activation
• ↑cAMP → phosphorylation of myosin light‑chain kinase inhibition
• Relaxation of bronchiolar smooth muscle and bronchodilation
• Inhibition of mast cell degranulation, reducing airway inflammation

Its high lipophilicity and rapid dissociation from receptors confer a bronchodilator effect lasting 12–24 h, ideal for twice‑daily dosing.

Pharmacokinetics

Half‑life: ~4–6 h (lung residence ~24 h).
*Note: Exposure is increased with CYP3A4 inhibitors (e.g., ketoconazole).*

Indications

• *Asthma*: long‑term maintenance – not for acute rescue.
• *COPD*: combination with inhaled corticosteroids or anticholinergics when β2‑agonist control is inadequate.
• *Allergic rhinitis*: in some preparations, as add‑on therapy.

Contraindications

• Absolute contraindication: hypersensitivity to β‑agonists, salmeterol, or excipients.
• Cardiovascular: untreated arrhythmias, severe hypertension, or ischemic heart disease; monitor for tachycardia, palpitations, and tremor.
• Drug interactions:
• *CYP3A4 inhibitors* → ↑salmeterol plasma levels.
• β–blockers → antagonize bronchodilation.
• *NSAIDs* may enhance β2‑agonist side effects.
• Warning: Not for acute bronchospasm; should not replace rescue β‑agonists.

Dosing

Preferred inhalation method: Metered-dose inhaler (MDI) or dry‑powder inhaler (DPI).
• *MDI*: 50 µg (two puffs) twice daily (BID).
• *DPI (GlaxoSmithKline Genuair/Pressair)*: 50 µg (one puff) BID.
• Administer via spacer if coordination issues are present.
• Pediatric dosing: ≥6 y : 50 µg BID; ≤6 y: 25 µg BID (per local guidelines).
• Pregnancy: Category C – only if benefits outweigh risks.
• Breastfeeding: Minimal transfer; considered acceptable in most cases.

Monitoring

• Peak expiratory flow (PEF) / spirometry baseline and periodic reassessment (every 4–12 weeks).
• Cardiovascular: heart rate, blood pressure, ECG if arrhythmia suspected.
• Serum potassium: check routinely in patients on concomitant diuretics or renal insufficiency.
• Pulmonary symptoms: frequency of rescue inhaler use; increase indicates inadequate control.

Clinical Pearls

• Respiratory action onset is ~30 min, but measurable bronchodilation extends to 12–24 h, making it suitable for nighttime dosing.
• Avoid using salmeterol solely for acute symptoms; designate short‑acting β2‑agonists (SABA) for rescue.
• Combine with inhaled corticosteroids (ICS) for synergistic anti‑inflammatory effects—especially in severe asthma or COPD with co‑existing eosinophilic inflammation.
• Use spacers with metered‑dose inhalers to improve drug delivery in children and elderly patients with coordination difficulty.
• Monitor potassium in patients on loop diuretics or potassium‑wasting steroids, as β2‑agonism can lower serum K⁺ and precipitate arrhythmias.
• CYP3A4 inhibitors (e.g., fluconazole, ketoconazole) can raise salmeterol levels; dose adjustment or alternative agents may be required.
• Pregnant patients: use the lowest effective dose; consider alternatives if the disease is poorly controlled.

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• Key pharmacology tags: *long‑acting β2‑agonist, LABA, bronchodilator, asthma maintenance, COPD therapy, inhalation pharmacokinetics, CYP3A4 interaction, cardiovascular monitoring, pediatric dosing, pregnancy considerations.*