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

Hypersensitivity to any component

Status asthmaticus or other acute episodes of asthma

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

Cautions

Cardiovascular disorder, convulsive disorder, thyrotoxicosis

Not to administer > twice daily dosing

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

Not for acute epidodes of COPD

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

Risk of hypokalemia, usually transient

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

Paradoxical bronchospasm may occur

Beta-2 agonists may increase serum glucose; use caution in patients with diabetes mellitus

Laryngeal spasm, swelling, irritation reported with use

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

Available data from controlled clinical trials suggest that LABA as monotherapy increase risk of asthma-related hospitalization in pediatric and adolescent patients; for pediatric and adolescent patients with asthma who require addition of a LABA to an ICS, a fixed-dose combination product containing both an ICS and a LABA should ordinarily be used to ensure adherence with both drugs; in cases where use of a separate ICS and a LABA is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components; if adherence cannot be assured, a fixed-dose combination product containing both an ICS and a LABA is recommended

Use only if not adequately controlled on asthma controller medications

Use only for shortest duration of time

Coadministration with CYP3A4 inhibitors may increase salmeterol levels and risk toxicity including QT prolongation

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%)