salmeterol (Rx)

>10%

Headache (13-17%)

Pain (1-12%)

1-10%

Nasal congestion (9%)

Hypertension (4%)

Edema (1-3%)

Dizziness (4%)

Sleep disturbance (1-3%)

Migraine (1-3%)

Contact dermatitis (1-3%)

Urticaria (3%)

Hyperglycemia (1-3%)

Articular rheumatism (1-3%)

Paresthesia (1-3%)

Muscular stiffness (1-3%)

Photodermatitis (1-2%)

Bronchitis (7%)

Influenza (5%)

Rigidity (1-3%)

hinitis (5%)

Asthma (3%)

Frequency Not Defined

Conjunctivitis

Hyperglycemia

Keratitis

Oral candidiasis

Chest tightness

Cataracts

Hypokalemia

Myositis

Contraindications

Severe hypersensitivity to milk proteins or demonstrated hypersensitivity to drug or excipients

Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required

Treatment of asthma without a concomitant long-term asthma control medication, such as an inhaled corticosteroid

Cautions

Use with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; therapy can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms; although such effects are uncommon after administration of salmeterol at recommended doses, if they occur, the drug may need to be discontinued

Drug should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result; clinically significant cardiovascular effects and fatalities reported in association with excessive use of inhaled sympathomimetic drugs; patients should not use another medicine containing a LABA (e.g., formoterol fumarate, arformoterol tartrate, indacaterol) for any reason

Use caution in diabetes mellitus and ketoacidosis; clinically significant and dose-related changes in blood glucose and/or serum potassium seen infrequently during clinical trials at recommended doses

Not for acute asthma; for acute asthma exacerbations, use short-acting beta-agonists (eg, albuterol)

Not for acute episodes of COPD

May increase risk of severe, potentially fatal asthma attacks; small but significant increase in asthma-related deaths for patients using salmeterol vs placebo, with greater risk in African-Americans

Therapy may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has potential to produce adverse cardiovascular effects; decrease in serum potassium is usually transient, not requiring supplementation

Use caution in patients with hypokalemia, hepatic impairment, seizure disorders, and hyperthyroidism

Paradoxical bronchospasm may occur with therapy; if it occurs it should be treated immediately with an inhaled, short-acting bronchodilator; treatment should be discontinued immediately and alternative therapy instituted; upper airway symptoms of laryngeal spasm, irritation, or swelling, such as stridor and choking, have been reported in patients receiving therapy

When initiating and throughout treatment in patients receiving oral or ICS for treatment of asthma, patients must continue taking a suitable dosage of corticosteroids to maintain clinical stability even if they feel better as a result of initiating salmeterol; any change in corticosteroid dosage should be made only after clinical evaluation

Use Serevent Diskus only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on an ICS; do not use Serevent Diskus for patients whose asthma is adequately controlled on low- or medium-dose ICS

Immediate hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur with therapy; anaphylactic reactions in patients with severe milk protein allergy after inhalation of powder products containing lactose reported

Use only for shortest duration of time

Deterioration of disease

• Not for use in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD, including patients with significantly increased symptoms
• Worsening or acutely deteriorating asthma is associated with increase in need for inhaled, short-acting beta2-agonists; decreasing response to usual medications; increasing need for systemic corticosteroids; recent emergency room visits; deteriorating lung function
• Increasing use of inhaled, short-acting beta2-agonists is a marker of deteriorating asthma; in this situation, the patient requires immediate reevaluation with reassessment of treatment regimen, giving special consideration to possible need for adding additional ICS or initiating systemic corticosteroids; patients should not use drug more than 1 inhalation twice daily

Drug interaction overview

• Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) not recommended because increased cardiovascular adverse effects may occur

Pregnancy

Available data from published epidemiological studies and case reports in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Beta-agonists may interfere with uterine contractility

There are clinical considerations in pregnant women with asthma

In women with poorly or moderately controlled asthma, there is increased risk of pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate

Severe asthma during pregnancy has been associated with maternal mortality, fetal mortality, or both

Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control

Animal data

• Oral administration of salmeterol to pregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternal doses approximately 50 times maximum recommended human daily inhaled dose (MRHDID) on an AUC basis

Labor and delivery

• There are no adequate and well-controlled human studies that have evaluated effects of therapy during labor and delivery; because of potential for beta-agonist interference with uterine contractility, use during labor should be restricted to those patients in whom the benefits clearly outweigh the risks

Lactation

There is no information regarding presence of salmeterol in human milk, effects on breastfed child, or on milk production

Drug is detected in rat milk; drug concentrations in human plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be low

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from treatment or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Long-acting beta-2 agonist; action on beta-2 receptors relaxes bronchial smooth muscle with little effect on heart rate

50 times more selective than albuterol

Pharmacokinetics

Peak serum time: 20 min

Half-Life: 5.5 hr

Onset: 30-48 min (asthma); 2 hr (COPD)

Duration: 12 hr

Absorption: Minimal (undetectable)

Protein Bound: 96%

Metabolism: Liver

Excretion: Feces (60%); urine (25%)