Skip to Content

Salmeterol

Pronunciation

Pronunciation

(sal ME te role)

Index Terms

  • Salmeterol Xinafoate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol Powder Breath Activated, Inhalation:

Serevent Diskus: 50 mcg/dose (28 ea, 60 ea) [contains lactose]

Brand Names: U.S.

  • Serevent Diskus

Pharmacologic Category

  • Beta2 Agonist
  • Beta2-Adrenergic Agonist, Long-Acting

Pharmacology

Relaxes bronchial smooth muscle by selective action on beta2-receptors with little effect on heart rate; salmeterol acts locally in the lung.

Absorption

Systemic: Inhalation: Undetectable to poor

Metabolism

Hepatic; hydroxylated via CYP3A4

Excretion

Feces (60%); urine (25%)

Onset of Action

Asthma: 30-48 minutes, COPD: 2 hours; Peak effect: Asthma: 3 hours, COPD: 2-5 hours

Time to Peak

Serum: ~20 minutes

Duration of Action

12 hours

Half-Life Elimination

5.5 hours

Protein Binding

96%

Special Populations: Hepatic Function Impairment

May lead to accumulation of salmeterol in plasma.

Use: Labeled Indications

Asthma/Bronchospasm: Treatment of asthma and the prevention of bronchospasm (only as concomitant therapy with a long-term asthma control medication, such as an inhaled corticosteroid), in patients 4 years and older with reversible obstructive airway disease, including patients with symptoms of nocturnal asthma.

Chronic obstructive pulmonary disease: Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis).

Exercise-induced bronchospasm: Prevention of exercise-induced bronchospasm (EIB) in patients 4 years and older (monotherapy may be indicated in patients without persistent asthma).

Limitations of use: Salmeterol is not indicated for the relief of acute bronchospasm.

Contraindications

Hypersensitivity to salmeterol or any component of the formulation (milk proteins); monotherapy in the treatment of asthma (ie, use without a concomitant long-term asthma control medication, such as an inhaled corticosteroid); treatment of status asthmaticus or other acute episodes of asthma or COPD

Canadian labeling: Additional contraindications (not in U.S. labeling): Presence of tachyarrhythmias

Documentation of allergenic cross-reactivity for sympathomimetics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Do not use for the relief of acute bronchospasm.

Asthma/Bronchospasm (maintenance and prevention): Inhalation: One inhalation twice daily (~12 hours apart); maximum: 1 inhalation twice daily. Note: For asthma control, long acting beta2-agonists (LABAs) should be used in combination with inhaled corticosteroids and not as monotherapy.

COPD (maintenance): Inhalation: One inhalation twice daily (~12 hours apart); maximum: 1 inhalation twice daily

Exercise-induced bronchospasm (prevention): Inhalation: One inhalation at least 30 minutes prior to exercise; additional doses should not be used for 12 hours; should not be used in individuals already receiving salmeterol twice daily. Note: Because LABAs may disguise poorly controlled persistent asthma, frequent or chronic use of LABAs for exercise-induced bronchospasm is discouraged by the Asthma Guidelines (NAEPP, 2007).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Do not use for the relief of acute bronchospasm.

Asthma/Bronchospasm (maintenance/prevention) and exercise-induced bronchospasm (prevention): Inhalation: Children ≥4 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution.

Administration

For oral inhalation route only. Before inhaling the dose, breath out fully; do not exhale into the Diskus device; activate and use only in a level, horizontal position. Inhale quickly and deeply through the Diskus; hold breath for about 10 seconds or for as long as comfortable and exhale slowly. Do not use with a spacer device or wash mouthpiece; Diskus should be kept dry. Discard device 6 weeks after removal from foil pouch or when the dose counter reads "0" (whichever comes first).

Dietary Considerations

Some products may contain lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Storage

Store at 68°F and 77°F (20°C and 25°C); excursions are permitted between 59°F and 86°F (15°C and 30°C). Protect from direct heat or sunlight. Store Diskus in the unopened foil pouch and only open when ready for use; stable for 6 weeks after removal from foil pouch.

Drug Interactions

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Salmeterol. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Salmeterol. Avoid combination

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Long-Acting Beta2-Agonists: May enhance the adverse/toxic effect of other Long-Acting Beta2-Agonists. Avoid combination

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

MAO Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Telaprevir: May increase the serum concentration of Salmeterol. Avoid combination

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tipranavir: May increase the serum concentration of Salmeterol. Avoid combination

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (13% to 17%)

Neuromuscular & skeletal: Pain (1% to 12%)

1% to 10%:

Cardiovascular: Hypertension (4%), edema (1% to 3%), pallor

Central nervous system: Dizziness (4%), sleep disturbance (1% to 3%), fever (1% to 3%), anxiety (1% to 3%), migraine (1% to 3%)

Dermatologic: Rash (1% to 4%), contact dermatitis (1% to 3%), eczema (1% to 3%), urticaria (3%), photodermatitis (1% to 2%)

Endocrine & metabolic: Hyperglycemia (1% to 3%)

Gastrointestinal: Throat irritation (7%), nausea (1% to 3%), dyspepsia (1% to 3%), dental pain (1% to 3%), gastrointestinal infection (1% to 3%), oropharyngeal candidiasis (1% to 3%), xerostomia (1% to 3%)

Hepatic: Liver enzymes increased

Neuromuscular & skeletal: Muscular cramps/spasm (3%), articular rheumatism (1% to 3%), arthralgia (1% to 3%), joint pain (1% to 3%), muscular stiffness (1% to 3%), paresthesia (1% to 3%), rigidity (1% to 3%)

Ocular: Keratitis/conjunctivitis (1% to 3%)

Respiratory: Nasal congestion (4% to 9%), tracheitis/bronchitis (7%), pharyngitis (≤6%), cough (5%), influenza (5%), viral respiratory tract infection (5%), sinusitis (4% to 5%), rhinitis (4% to 5%), asthma (3% to 4%)

<1% (Limited to important or life-threatening): Abdominal pain, agitation, aggression, anaphylactic reaction (some in patients with severe milk allergy [Diskus®]), angioedema, aphonia, arrhythmia, atrial fibrillation, cataracts, chest congestion, chest tightness, choking, contusions, Cushing syndrome, Cushingoid features, depression, dysmenorrhea, dyspnea, earache, ecchymoses, edema (facial, oropharyngeal), eosinophilic conditions, glaucoma, growth velocity reduction in children/adolescents, hypercorticism, hypersensitivity reaction (immediate and delayed), hypokalemia, hypothyroidism, intraocular pressure increased, laryngeal spasm/irritation, irregular menstruation, myositis, oropharyngeal irritation, osteoporosis, pallor, paradoxical bronchospasm, paradoxical tracheitis, paranasal sinus pain, PID, QTc prolongation, restlessness, stridor, supraventricular tachycardia, syncope, tremor, vaginal candidiasis, vaginitis, vulvovaginitis, rare cases of vasculitis (Churg-Strauss syndrome), ventricular tachycardia, weight gain

ALERT: U.S. Boxed Warning

Asthma-related death:

Long-acting beta-2 adrenergic agonists, such as salmeterol, increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of salmeterol or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,176 patients treated for 28 weeks on salmeterol versus 3 deaths out of 13,179 patients on placebo). Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from long-acting beta-2 adrenergic agonists.

Because of this risk, use of salmeterol for the treatment of asthma without a concomitant long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated. Use salmeterol only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (eg, discontinue salmeterol) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use salmeterol for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

Pediatric and adolescent patients:

Available data from controlled clinical trials suggest that long-acting beta-2 adrenergic agonists increase the risk of asthma-related hospitalization in pediatric and adolescent patients. For pediatric and adolescent patients with asthma who require addition of a long-acting beta-2 adrenergic agonist to an inhaled corticosteroid, a fixed-dose combination product containing both an inhaled corticosteroid and a long-acting beta-2 adrenergic agonist should ordinarily be used to ensure adherence with both drugs. In cases where use of a separate long-term asthma control medication (eg, inhaled corticosteroid) and a long-acting beta-2 adrenergic agonist is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components. If adherence cannot be ensured, a fixed-dose combination product containing both an inhaled corticosteroid and a long-acting beta-2 adrenergic agonist is recommended.

Warnings/Precautions

Concerns related to adverse effects:

• Appropriate use: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

• Asthma-related deaths: [U.S. Boxed Warning]: Long-acting beta2-agonists (LABAs) increase the risk of asthma-related deaths. Salmeterol should only be used in asthma patients as adjuvant therapy in patients who are currently receiving but are not adequately controlled on a long-term asthma control medication (ie, an inhaled corticosteroid). Monotherapy with an LABA is contraindicated in the treatment of asthma. In a large, randomized, placebo-controlled U.S. clinical trial (SMART, 2006), salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy); risk is considered a class effect among all LABAs. Data are not available to determine if the addition of an inhaled corticosteroid lessens this increased risk of death associated with LABA use. Assess patients at regular intervals once asthma control is maintained on combination therapy to determine if step-down therapy is appropriate and the LABA can be discontinued (without loss of asthma control), and the patient can be maintained on an inhaled corticosteroid. LABAs are not appropriate in patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

• Bronchospasm: Rarely, paradoxical bronchospasm, which may be life threatening, may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.

• Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, have been reported.

• Upper airway symptoms: There have been reports of laryngeal spasm, irritation, swelling (stridor, choking) with use.

Disease-related concerns:

• Asthma: Appropriate use: Do not use for acute bronchospasm. Short-acting beta2-agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. Do not initiate in patients with significantly worsening or acutely deteriorating asthma; reports of severe (sometimes fatal) respiratory events have been reported when salmeterol has been initiated in this situation. Corticosteroids should not be stopped or reduced when salmeterol is initiated. During initiation, watch for signs of worsening asthma.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, or hypertension); beta-agonists may cause elevation in blood pressure, heart rate and result in CNS stimulation/excitation. Beta2-agonists may also increase risk of arrhythmias and electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.

• COPD: Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Data are not available to determine if LABA use increases the risk of death in patients with COPD. Canadian labeling suggest concurrent use of oral or inhaled corticosteroids may not be necessary in COPD because the role of inhaled corticosteroids is less well established; concurrent use should be determined by the treating physician.

• Diabetes: Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose and aggravate ketoacidosis.

• Exercise-induced bronchospasm: Because LABAs may disguise poorly controlled persistent asthma, frequent or chronic use of LABAs for exercise-induced bronchospasm is discouraged by the NIH Asthma Guidelines (NIH, 2007).

• Hepatic impairment: Use with caution in patients with hepatic impairment. Salmeterol is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of salmeterol in plasma.

• Hyperthyroidism: Use with caution in hyperthyroidism; may stimulate thyroid activity.

• Hypokalemia: Use with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium, possibly through intracellular shunting. This effect is usually transient.

• Seizures: Use with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: [U.S. Boxed Warning]: LABAs may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. In general, a combination product containing a LABA and an inhaled corticosteroid is preferred in patients <18 years of age to ensure compliance.

Dosage form specific issues:

• Lactose: Powder for oral inhalation contains lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Other warnings/precautions:

• Patient information: Patients must be instructed to use inhaled short-acting beta2-agonists (eg, albuterol) for acute asthmatic or COPD symptoms and to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of inhaled short-acting beta2-agonist may indicate deterioration of asthma, and medical evaluation must not be delayed. Salmeterol should not be used more than twice daily; do not use with other long-acting beta2-agonists.

Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium. Monitor for increased use of short-acting beta2-agonist inhalers; may be marker of a deteriorating asthma condition.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Beta-agonists have the potential to affect uterine contractility if administered during labor.

Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Although data related to its use in pregnancy is limited, salmeterol may be used when a long-acting beta agonist is needed to treat moderate persistent or severe persistent asthma in pregnant women (NAEPP, 2005).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinitis, pharyngitis, cough, or rhinorrhea. Have patient report immediately to prescriber signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), angina, tachycardia, severe anxiety, severe headache, severe dizziness, tremors, difficulty breathing, wheezing, or severe cough (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide