Usage
Formoterol is a long-acting beta2-adrenergic agonist (LABA) prescribed for the long-term maintenance treatment of asthma and chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is also used to prevent exercise-induced bronchospasm (EIB). It belongs to the bronchodilator class of medications.
Formoterol works by relaxing the smooth muscles in the airways, which allows air to flow more easily into the lungs.
Alternate Names
Formoterol is also known as eformoterol. Brand names include Foradil Aerolizer, Perforomist, and Formoterol Easyhaler. Formoterol is often combined with inhaled corticosteroids such as budesonide (Symbicort, Breyna) and mometasone (Dulera).
How It Works
Pharmacodynamics: Formoterol acts as a selective agonist at beta2-adrenergic receptors, predominantly in the lungs. Stimulation of these receptors activates adenylate cyclase, leading to an increase in intracellular cyclic adenosine monophosphate (cAMP). Increased cAMP levels promote relaxation of bronchial smooth muscle, resulting in bronchodilation. It also inhibits the release of mast cell mediators, like histamine and leukotrienes, which contribute to inflammation and bronchoconstriction.
Pharmacokinetics: Formoterol, whether inhaled or nebulized, is rapidly absorbed into the systemic circulation. The duration of action is approximately 12 hours, allowing for twice-daily dosing. It is primarily metabolized in the liver and excreted primarily via renal pathways. Specific CYP450 isoenzymes involved in metabolism have not been definitively characterized.
Mode of Action: Formoterol binds to beta2-adrenergic receptors on the surface of bronchial smooth muscle cells. This binding triggers a cascade of intracellular events, ultimately leading to smooth muscle relaxation and bronchodilation.
Receptor Binding: Formoterol selectively binds to beta2-adrenergic receptors, although at high doses, some interaction with beta1-adrenergic receptors in the heart may occur, potentially leading to cardiovascular side effects.
Elimination Pathways: Formoterol is primarily metabolized in the liver and eliminated through renal excretion.
Dosage
Standard Dosage
Adults:
- Asthma and COPD: 12 mcg inhaled twice daily. The maximum daily dose is 48 mcg. If using formoterol as a nebulized solution, 20 mcg twice daily is recommended. The maximum daily dose via nebulization is 40 mcg.
- EIB: 12 mcg inhaled at least 15 minutes before exercise, as needed, but not more frequently than every 12 hours.
Children:
- Less than 5 years: Not recommended for use in children younger than 5 years old.
- 5 years and older: 12 mcg inhaled twice daily for asthma and COPD. 12 mcg inhaled at least 15 minutes before exercise for EIB, as needed.
- 6 to 12 years: Formoterol may be given in combination with an inhaled corticosteroid (ICS). Dosage for asthma maintenance in this age group varies depending on the specific ICS and formoterol combination product.
Special Cases:
- Elderly Patients: Dosage adjustments are generally not necessary, but it should be used cautiously in patients over 65 years of age.
- Patients with Renal Impairment: No dosage adjustments are typically needed.
- Patients with Hepatic Dysfunction: Patients with severe liver cirrhosis may require a dosage reduction, as formoterol is primarily metabolized in the liver.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, diabetes, hyperthyroidism, and seizure disorders. Dose adjustment may be needed.
Clinical Use Cases
Formoterol is not typically recommended for intubation, surgical procedures, mechanical ventilation, ICU use, or acute emergency situations like status asthmaticus or cardiac arrest. Short-acting bronchodilators or other emergency medications are preferred in these settings.
Dosage Adjustments
Dosage adjustments may be needed based on the patient’s individual response, concomitant medications (particularly drug interactions), and clinical condition.
Side Effects
Common Side Effects
- Headache
- Muscle cramps
- Tremor
- Dizziness
- Nervousness
- Insomnia
- Dry mouth
- Nausea, vomiting, diarrhea
- Upper respiratory tract infections
- Sore throat
Rare but Serious Side Effects
- Severe allergic reactions (anaphylaxis): swelling of face, throat, tongue, lips, difficulty breathing, hives, rash, itching
- Paradoxical bronchospasm (worsening of breathing)
- Cardiac arrhythmias (irregular heartbeats), palpitations, tachycardia
- Hypokalemia (low potassium)
- Hyperglycemia (high blood sugar)
Long-Term Effects
Long-term use of LABAs, including formoterol, may be associated with a slight increase in the risk of severe asthma exacerbations. Regular monitoring is important.
Adverse Drug Reactions (ADR)
Clinically significant ADRs may include severe allergic reactions, paradoxical bronchospasm, and cardiac arrhythmias. These require immediate medical intervention.
Contraindications
- Hypersensitivity to formoterol or any component of the formulation
- Primary treatment of status asthmaticus or other acute episodes of asthma or COPD requiring intensive measures, especially in fixed-combination products.
- Use of formoterol without concomitant inhaled corticosteroids in asthma treatment is contraindicated.
Drug Interactions
- Beta-blockers (including eye drops): Can block the bronchodilating effects of formoterol and may cause severe bronchospasm.
- Diuretics, xanthine derivatives, steroids: May potentiate hypokalemia.
- Tricyclic antidepressants, some antiarrhythmics (e.g., disopyramide): May prolong the QT interval and increase the risk of ventricular arrhythmias.
- MAO inhibitors: May enhance the effects of formoterol.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): May increase formoterol levels, requiring close monitoring for adverse effects.
Pregnancy and Breastfeeding
- Pregnancy: Formoterol should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Studies in animals have shown some adverse reproductive effects. Consider potential benefits and risks to the fetus. Use only if deemed essential for asthma control.
- Breastfeeding: It is not known whether formoterol passes into human breast milk. Caution is advised while using formoterol during breastfeeding. Consult with healthcare provider to assess risks and benefits and consider the mother’s clinical needs.
Drug Profile Summary
- Mechanism of Action: Beta2-adrenergic agonist, relaxes bronchial smooth muscle, leading to bronchodilation.
- Side Effects: Common: headache, tremor, nervousness. Serious: allergic reactions, paradoxical bronchospasm, cardiac arrhythmias.
- Contraindications: Hypersensitivity, primary treatment of status asthmaticus, use without ICS in asthma.
- Drug Interactions: Beta-blockers, diuretics, tricyclic antidepressants, MAO inhibitors, CYP3A4 inhibitors.
- Pregnancy & Breastfeeding: Use with caution. Weigh potential benefits and risks.
- Dosage: Adults and children ≥5 years: 12 mcg inhaled twice daily for asthma and COPD. EIB: 12 mcg 15 minutes before exercise.
- Monitoring Parameters: Lung function (peak flow, FEV1), blood glucose, serum potassium, heart rate, blood pressure, and signs of allergic reaction.
Popular Combinations
Formoterol is commonly combined with inhaled corticosteroids (ICS) such as:
- Budesonide: Symbicort, Breyna. This combination provides both anti-inflammatory and bronchodilator effects for better asthma and COPD control.
- Mometasone: Dulera. This combination also provides both anti-inflammatory and bronchodilator effects.
Precautions
- General Precautions: Monitor for paradoxical bronchospasm, cardiovascular effects (e.g., increased heart rate, palpitations), and hypokalemia.
- Specific Populations: Pregnant women, breastfeeding mothers, children younger than 5 years, and patients with cardiovascular disease, diabetes, hyperthyroidism, or seizure disorders.
- Lifestyle Considerations: Inform patients about proper inhaler technique, potential side effects, and when to seek medical attention.
FAQs (Frequently Asked Questions)
A: Adults and children 5 years and older: 12 mcg inhaled twice daily for asthma and COPD. For EIB, 12 mcg at least 15 minutes before exercise.
A: No, formoterol should not be used as monotherapy for long-term asthma control. It should always be used in conjunction with an inhaled corticosteroid.
A: Common side effects include headache, tremor, palpitations, nervousness, and dizziness.
Q4: What should patients do if they experience paradoxical bronchospasm?
A: Patients should discontinue Formoterol immediately and seek emergency medical attention.
A: Formoterol is a long-acting beta2-agonist (LABA) with a duration of action of about 12 hours, while SABAs, such as albuterol, provide rapid but shorter relief (4-6 hours). LABAs are for maintenance therapy, while SABAs are for quick relief of symptoms.
A: Formoterol should be used during pregnancy and breastfeeding only if the potential benefit outweighs the potential risk. Consult with a healthcare provider for individualized assessment.
A: Formoterol is available as a dry powder inhaler, metered-dose inhaler, and solution for nebulization. Patients must receive instructions on the proper technique for their prescribed device.
A: Signs of a serious allergic reaction include swelling of the face, lips, tongue, or throat; difficulty breathing or swallowing; hives; severe itching; and rash. Immediate medical attention is required if these occur.
A: The maximum daily dose for adults is 48 mcg for inhaled formoterol and 40 mcg for nebulized formoterol. For children 5 years and older using an inhaler, it’s also 48 mcg.
A: No, Formoterol is not indicated for the relief of acute asthma symptoms. A short-acting beta2-agonist (SABA) like albuterol is the preferred treatment for acute exacerbations.
