Salmeterol

Trade Names:Serevent Diskus- Inhalation powder 50 mcg (as salmeterol xinafoate salt)

Pharmacology

Produces bronchodilation by relaxing bronchial smooth muscle through beta-2 receptor stimulation.

Pharmacokinetics

Absorption

Salmeterol acts locally in the lung. Plasma levels do not predict therapeutic effect. Depending on dose, T _max is 5 to 45 min, and mean C _max is 167 pg/mL.

Distribution

Protein binding is 96%; xinafoate moiety is greater than 99%.

Metabolism

Extensively metabolized by hydroxylation.

Elimination

Eliminated in feces (60%) and urine (25%); t _½ is 6 days. Xinafoate moiety is 11 days.

Special Populations

Has not been studied in patients with renal function impairment.

May lead to accumulation of salmeterol in plasma.

Indications and Usage

Maintenance treatment of asthma and prevention of bronchospasm with reversible obstructive airway disease; prevention of exercise-induced bronchospasm; maintenance treatment of bronchospasm associated with COPD (including emphysema and chronic bronchitis).

Contraindications

Standard considerations.

Dosage and Administration

Inhalation 1 inhalation (50 mcg) twice daily, approximately 12 h apart.

Inhalation 1 inhalation at least 30 min before exercise; additional doses should not be used for up to 12 h.

Inhalation 1 inhalation (50 mcg) twice daily, approximately 12 h apart.

General Advice

• If patient is also receiving short-acting bronchodilator by inhalation, administer short-acting bronchodilator 5 min before salmeterol to enhance penetration of latter drug into bronchial tree.
• Not for use in conjunction with inhaled, long-acting beta-2 agonist.

Storage/Stability

Store at controlled room temperature (68° to 77°F) in a dry place. Protect from direct heat or sunlight. Discard 6 wk after removal from moisture-protective foil pouch or when the dose indicator reads “0.”

Drug Interactions

Pulmonary effects of salmeterol may be blocked and may produce severe bronchospasm in patients with COPD.

ECG changes and hypokalemia associated with diuretics may worsen with coadministration.

May increase CV effects of salmeterol.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (4%); palpitations, tachycardia; arrhythmias, including atrial fibrillation, extrasystoles, and supraventricular tachycardia (postmarketing).

CNS

Headache (17%); dizziness (4%); anxiety, migraine, nervousness, paresthesia, sleep disturbance, tremor (1% to 3%).

Dermatologic

Rash (4%); urticaria (3%); contact dermatitis, eczema (1% to 3%); photodermatitis (1% to 2%).

EENT

Nasal sinus congestion, pallor (9%); throat irritation (7%); pharyngitis (6%); rhinitis (5%); ear signs/symptoms, nasal blockage/congestion, sinusitis (4%); conjunctivitis, keratitis, sinus headache (1% to 3%).

GI

Nausea/vomiting (3%); dental pain, dyspepsia, GI infections, hyposalivation, oral candidiasis, oral mucosal abnormality (1% to 3%); GI signs/symptoms (1% to 2%).

Hypersensitivity

Immediate hypersensitivity reactions (eg, angioedema, bronchospasm, rash); anaphylaxis (postmarketing).

Musculoskeletal

Skeletal muscle pain (12%); muscle cramps/spasms (3%); arthralgia, articular rheumatism, bone/skeletal pain, inflammation, muscle pain, muscle stiffness, pain in joints, tightness, rigidity (1% to 3%).

Respiratory

Bronchitis, tracheitis (7%); cough, viral respiratory infection (5%); asthma (4%); lower respiratory signs/symptoms (1% to 3%); irritation or swelling (including stridor or choking), laryngeal spasm, oropharyngeal irritation, paradoxical bronchospasm, serious (some fatal) exacerbations of asthma (postmarketing).

Miscellaneous

Influenza (5%); body pain, edema, fever, hyperglycemia, pain, swelling (1% to 3%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Not recommended for children younger than 4 yr of age.

Hypersensitivity

Allergic reactions can occur after administration.

Acute asthma attacks

Do not use to treat acute symptoms.

CV disease

Use with caution in patients with CV disease; toxic symptoms may occur.

Excessive use

Paradoxical bronchospasm and cardiac arrest have been associated with excessive inhalant use.

Hypokalemia

Decreases in potassium levels may occur.

Paradoxical bronchospasm

Life-threatening paradoxical bronchospasm may occur.

Worsening or acutely deteriorating asthma

Do not initiate salmeterol in this setting.

Overdosage

Symptoms

Arrhythmias and/or tachycardia, cardiac arrest, death, headache, hyperglycemia, hypokalemia, muscle cramps, palpitations, prolongation of the QTc interval, tremor.

Patient Information

• Instruct patient on the proper storage, handling, and use of the dry powder inhaler, referring to the patient information leaflet included with the medication.
• Advise patient that medication should never be administered with a spacer device.
• Caution patient not to exceed prescribed dose. Inform patient that medication is still inhaled even if not tasted or felt when delivered.
• Instruct patient not to stop the medication once symptoms have been controlled. Continued daily use is necessary to continue control of symptoms.
• Advise patient not to change the dose or stop using unless advised by health care provider.
• Caution patient not to use other salmeterol-containing products or other long-acting bronchodilators while using salmeterol.
• Warn patient that salmeterol is a maintenance medication and is not to be used to treat an acute asthma attack. “Rescue medication” (short-acting bronchodilator) must be used to obtain rapid relief of asthma symptoms.
• Advise patient using salmeterol for prevention of exercise-induced bronchospasm to take medication at least 30 to 60 min before exercise and to wait 12 h before using again.
• Advise patient that medication does not replace inhaled or oral corticosteroids and to continue to use as prescribed by health care provider.
• Advise patient not to increase dose and to inform health care provider if symptoms do not improve or worsen or if more short-acting bronchodilator than usual is needed or if short-acting bronchodilator appears to become less effective.
• Advise patient to carry medical identification (eg, card, bracelet) if experiencing acute severe asthma attacks requiring rapid systemic treatment.
• Advise patient to report the following symptoms to health care provider: chest pain, nervousness, palpitations, persistent cough, rapid heart rate, sore throat or mouth, tremor, worsening asthma symptoms.

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