Brands, Medical Use, Clinical Data
- Bronchodilator Agents
- Adrenergic beta-Agonists
- Metered-dose (aerosol)
Brands / Synonyms
Advair Diskus; Advair HFA; Aeromax; Arial; Astmerole; Fujimycin; Salmetedur; Salmeterolum [Latin]; Serevent
For the treatment of asthma and chronic obstructive pulmonary disease (COPD).
Salmeterol is a long acting beta2-adrenoceptor agonist (LABA), usually only prescribed for severe persistent asthma following previous treatment with a short-acting beta agonist such as salbutamol and is prescribed concurrently with a corticosteroid, such as beclometasone. The primary noticable difference of salmeterol to salbutamol is that the duration of action lasts approximately 12 hours in comparison with 4-6 hours of salbutamol. When used regularly every day as presecribed, inhaled salmeterol decreases the number and severity of asthma attacks. However, it is not for use for relieving an asthma attack that has already started. Inhaled salmeterol works like other beta 2-agonists, causing bronchodilatation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma. Salmeterol is similar in action to formoterol, however formoterol has been demonstrated to have a faster onset of action than salmeterol as a result of a lower lipophilicity, and has also been demonstrated to be more potent - a 12 µg dose of formoterol has been demonstrated to be equivalent to a 50 µg dose of salmeterol.
Mechanism of Action
Salmeterol's long, lipophilic side chain binds to exosites near beta(2)-receptors in the lungs and on bronchiolar smooth muscle, allowing the active portion of the molecule to remain at the receptor site, continually binding and releasing. Beta(2)-receptor stimulation in the lung causes relaxation of bronchial smooth muscle, bronchodilation, and increased bronchial airflow.
Because of the small therapeutic dose, systemic levels of salmeterol are low or undetectable after inhalation of recommended doses.
Symptoms of overdose include angina (chest pain), dizziness, dry mouth, fatigue, flu-like symptoms, headache, heart irregularities, high or low blood pressure, high blood sugar, insomnia, muscle cramps, nausea, nervousness, rapid heartbeat, seizures, and tremor. By the oral route, no deaths occurred in rats at 1,000 mg/kg (approximately 81,000 times the maximum recommended daily inhalation dose in adults and approximately 38,000 times the maximum recommended daily inhalation dose in children on a mg/m2 basis).
Biotrnasformation / Drug Metabolism
Hepatic, metabolized by hydroxylation via CYP3A4
SEREVENT DISKUS is contraindicated in patients with a history of hypersensitivity to salmeterol or any
other component of the drug product.
Short-Acting Beta2-Agonists: In two 12-week, repetitive-dose adolescent and adult clinical trials in patients with
asthma (N = 149), the mean daily need for additional beta2-agonist in patients using SEREVENT DISKUS was approximately
1½ inhalations/day. Twenty-six percent (26%) of the patients in these trials used between 8 and 24 inhalations of short-
acting beta-agonist per day on 1 or more occasions. Nine percent (9%) of the patients in these trials averaged over 4
inhalations/day over the course of the 12-week trials. No increase in frequency of cardiovascular events was observed
among the 3 patients who averaged 8 to 11 inhalations/day; however, the safety of concomitant use of more than 8 inhalations/day
of short-acting beta2-agonist with SEREVENT DISKUS has not been established. In 29 patients who experienced worsening of asthma
while receiving SEREVENT DISKUS during these trials, albuterol therapy administered via either nebulizer or inhalation aerosol
(1 dose in most cases) led to improvement in FEV1 and no increase in occurrence of cardiovascular adverse events.
In 2 clinical trials in patients with COPD, the mean daily need for additional beta2-agonist for patients using SEREVENT DISKUS
was approximately 4 inhalations/day. Twenty-four percent (24%) of the patients using SEREVENT DISKUS in these trials averaged 6
or more inhalations of albuterol per day over the course of the 24-week trials. No increase in frequency of cardiovascular events
was observed among patients who averaged 6 or more inhalations per day.
Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: Salmeterol should be administered with extreme caution to patients
being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents,
because the action of salmeterol on the vascular system may be potentiated by these agents.
Corticosteroids and Cromoglycate: In clinical trials, inhaled corticosteroids and/or inhaled cromolyn sodium did not alter the
safety profile of salmeterol when administered concurrently.
Methylxanthines: The concurrent use of intravenously or orally administered methylxanthines (e.g., aminophylline, theophylline)
by patients receiving salmeterol has not been completely evaluated. In 1 clinical asthma trial, 87 patients receiving SEREVENT
Inhalation Aerosol 42 mcg twice daily concurrently with a theophylline product had adverse event rates similar to those in 71
patients receiving SEREVENT Inhalation Aerosol without theophylline. Resting heart rates were slightly higher in the patients on
theophylline but were little affected by therapy with SEREVENT Inhalation Aerosol.
In 2 clinical trials in patients with COPD, 39 subjects receiving SEREVENT DISKUS concurrently with a theophylline product had
adverse event rates similar to those in 302 patients receiving SEREVENT DISKUS without theophylline. Based on the available data,
the concomitant administration of methylxanthines with SEREVENT DISKUS did not alter the observed adverse event profile.
Beta-Adrenergic Receptor Blocking Agents: Beta-blockers not only block the pulmonary effect of beta-agonists, such as SEREVENT
DISKUS, but may also produce severe bronchospasm in patients with asthma or COPD. Therefore, patients with asthma or COPD should
not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction,
there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma or COPD. In this
setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
Diuretics: The ECG changes and/or hypokalemia that may result from the administration of nonpotassium-sparing diuretics (such as
loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is
exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-
agonists with nonpotassium-sparing diuretics.