What are the side effects of formoterol (long-acting beta2-adrenergic receptor agonist)?

Side Effects of Formoterol (Long-Acting Beta2-Adrenergic Receptor Agonist)

Formoterol can cause several side effects ranging from mild to serious, with the most concerning being an increased risk of asthma-related death when used as monotherapy in asthma patients. 1

Common Side Effects

• Cardiovascular effects:

  • Palpitations and tachycardia 1
  • Increased risk of cardiovascular events (2.7% vs 0.7% with placebo) 2
  • Chest pain (1.9% vs 1.3% with placebo) 1

• Neurological effects:

  • Tremor (1.9% vs 0.4% with placebo) - dose-related 1
  • Dizziness (1.6% vs 1.5% with placebo) - dose-related 1
  • Headache 3
  • Insomnia (1.5% vs 0.8% with placebo) 1

• Metabolic effects:

  • Reduced serum potassium (hypokalemia) 2, 3
  • Hyperglycemia 1
  • Metabolic acidosis 1

• Respiratory effects:

  • Viral infections (17.2% vs 17.1% with placebo) 1
  • Bronchitis (4.6% vs 4.3% with placebo) 1
  • Chest infection (2.7% vs 0.4% with placebo) 1
  • Dyspnea (2.1% vs 1.7% with placebo) 1
  • Dysphonia (1.0% vs 0.9% with placebo) - dose-related 1

• Other effects:

  • Dry mouth 1
  • Muscle cramps 1
  • Rash (1.1% vs 0.7% with placebo) 1

Serious Side Effects

• Asthma-related adverse events:

  • Increased risk of asthma-related death (FDA black box warning) 1
  • Serious asthma exacerbations requiring hospitalization (0.6% with 12 mcg twice daily vs 0.2% with placebo) 1
  • Higher risk of severe exacerbations with higher doses (24 mcg twice daily) 1

• Severe cardiovascular effects:

  • Angina 1
  • Hypertension or hypotension 1
  • Arrhythmias 1
  • Increased risk of atrial fibrillation, particularly in patients with COPD or asthma and structural heart disease 2

• Rare but serious reactions:

  • Anaphylactic reactions including severe hypotension and angioedema 1

Special Considerations

Risk Factors for Adverse Effects

• Pre-existing cardiac conditions:

  • Patients with pre-existing cardiac arrhythmias and hypoxemia are at higher risk for cardiac adverse effects 4
  • Higher doses (24 mcg) show more cardiac effects than lower doses (12 mcg) 4

• Age and disease state:

  • Children with asthma may experience different adverse event patterns, with more infections/inflammation and abdominal complaints 1
  • COPD patients may have different side effect profiles than asthma patients 1

Tachyphylaxis

• Tachyphylaxis (reduced response over time) to the bronchoprotective effect occurs with regular use 2, 3
• Tachyphylaxis to the bronchodilator effect is more likely with formoterol (full agonist) than with salmeterol (partial agonist) 3

Important Warnings and Precautions

• Never use formoterol as monotherapy for asthma - it should always be used in combination with inhaled corticosteroids 2
• The FDA has added warnings about the safety of long-acting beta agonists due to increased risk of severe exacerbations and deaths 2
• Higher doses are associated with greater risk of serious adverse events 1
• Regular monitoring is recommended, especially in patients with cardiovascular risk factors 4
• Formoterol may mask worsening of underlying inflammatory conditions due to its potent bronchodilatory effects 2

By understanding these side effects and following appropriate precautions, healthcare providers can better manage patients requiring formoterol therapy while minimizing risks.