Formoterol
Formoterol
Generic Name
Formoterol
Mechanism
- Selective β₂‑adrenergic receptor agonist → ↑ intracellular cAMP via adenylyl cyclase activation.
- Smooth‑muscle relaxation → bronchodilation of tracheobronchial smooth muscle.
- Prolonged receptor activation (~12 h) due to high affinity and slow dissociation from β₂ receptors.
- Minor anti‑inflammatory effects through β₂ stimulation of eosinophil apoptosis and down‑regulation of pro‑inflammatory cytokines.
Pharmacokinetics
| Parameter | Typical Value |
| Bioavailability (inhaled) | ~70 % (due to local first‑pass metabolism) |
| Peak concentration (Cmax) | 30–120 min post‑inhalation (variable by device) |
| Half‑life | 3–4 h systemic; lung effect persists >12 h |
| Metabolism | CYP2D6‑mediated hepatic ester hydrolysis → inactive metabolites |
| Elimination | Renal (~30 %) and fecal (bile excretion) |
| Drug interactions | Minimal; caution with CYP2D6 inhibitors (fluoxetine, paroxetine) may modestly increase levels |
| Special populations | No dose adjustment needed for mild renal or hepatic impairment; caution in severe heart disease |
Indications
- Maintenance therapy for asthma (≥12 y) – improves lung function and reduces exacerbations.
- Maintenance treatment for COPD (≥18 y) – often combined with inhaled corticosteroids (FDCs).
- Combination with inhaled corticosteroids – for patients requiring dual bronchodilation; e.g., Formoterol/Fluticasone.
Contraindications
- Known hypersensitivity to formoterol or any excipient.
- Uncontrolled cardiovascular disease: tachyarrhythmias, ischemic heart disease, severe hypertension.
- Use with caution in:
- Congestive heart failure (especially with β₂‑agonist–pretreated patients).
- Severe pulmonary hypertension.
- Concurrent use of systemic β‑agonists or steroids requiring close monitoring.
- Pregnancy & lactation: Category B; limited data – use only if benefits outweigh risks.
- Pediatric (<12 y): Not approved for maintenance use; investigational safety data.
Dosing
| Formulation | Dose/Device | Frequency | Note |
| Hand‑held Metered‑Dose Inhaler (MDI) | 100 µg per actuation (1–2 puffs) | Twice daily (q12 h) | Use spacer; perform lung‑delivery technique check. |
| Dry‑Powder Inhaler (DPI) | 90 µg per actuation (1–2 puffs) | Twice daily | Ensure proper inspiratory effort. |
| Inhaled Combination (Formoterol + Fluticasone) | 100 µg/250 µg per actuation | Twice daily | Titration based on symptom control; may transition to once-daily in stable COPD. |
*Maximum daily dose:* 400 µg (MDI) or 360 µg (DPI).
Adverse Effects
- Common (≤2 % incidence)
- Tremor, headache, palpitations
- Dry mouth, sore throat
- Headache‑induced GI upset
- Serious/Moderate (1–2 % incidence)
- Palpitations progressing to arrhythmia (VT, SVT)
- Hypokalemia (especially with high dose or concurrent loop diuretics)
- Seizures (rare, potentially precipitated by hypokalemia)
- Myopathy with long‑term high‑dose use
- Other (rare)
- Hypersensitivity rash, itching
- Broncho‑laryngitis
Monitoring
| Parameter | Frequency | Rationale |
| Spirometry (FEV₁, FVC) | Every 4–6 weeks (or as clinically indicated) | Assess bronchodilator efficacy. |
| Blood pressure & heart rate | Baseline, then after first dose, and periodically during therapy | Detect cardiovascular side effects. |
| Serum potassium | Baseline, then every 3–6 months (in COPD or with diuretics) | Prevent hypokalemia‑induced arrhythmia. |
| Adverse effect reporting | Continuous, patient‑directed diary of tremor, palpitations, etc. | Early detection of toxicity. |
| Inhaler technique audit | Every visit (≥3 months) | Ensure optimal drug delivery and avoid under‑dosing. |
Clinical Pearls
1. “Rapid Onset, Long Duration” Dichotomy
Formoterol’s onset (5–10 min) rivals short‑acting β₂ agonists, yet its action persists >12 h. Consequently, it is sometimes used as a rescue bronchodilator in severe exacerbations only when no short‑acting β₂ is available.
2. Avoid Over‑Use with Short‑Acting β₂
Because Formoterol’s systemic absorption can precipitate arrhythmias, combine cautiously with albuterol or salbutamol. Document dosage to avoid additive cardiotoxicity.
3. Spacer Devices Boost Efficacy & Reduce Systemic Exposure
A spacer can increase % of drug reaching the lungs, reducing tremor and tachycardia rates by up to 30 % relative to uns-spaced MDIs.
4. Dose Titration in Asthma‑COPD Overlap
In patients with both asthma and COPD, start at the lowest therapeutic dose (1 puff twice daily) and titrate up while monitoring PFTs and ECG.
5. Hypokalemia Check in Elderly and Diuretic Users
In older adults and those on loop diuretics, baseline serum potassium <3.8 mmol/L warrants dose reduction or potassium supplementation before initiating Formoterol.
6. Use of Combination FDCs Reduces Exacerbation Risk
Formoterol/Fluticasone FDCs lower exacerbations by ~25 % versus monotherapy in moderate‑to‑severe asthma. This is a primary reason for widespread adoption.
By integrating these key points, practitioners can maximize therapeutic benefit while minimizing adverse outcomes—ensuring that Formoterol remains a cornerstone in bronchodilator therapy.