Pronunciation

U.S. Brand Names

Serevent® Diskus®

Synonyms

Salmeterol Xinafoate

Generic Available

No

Canadian Brand Names

Serevent®

Use

Maintenance treatment of asthma and in prevention of bronchospasm with reversible obstructive airway disease, including patients with symptoms of nocturnal asthma, who require regular treatment with inhaled, short-acting beta2 agonists; prevention of exercise-induced bronchospasm; maintenance treatment of bronchospasm associated with COPD

Pregnancy Risk Factor

C

Lactation

Enters breast milk/use caution

Contraindications

Hypersensitivity to salmeterol, adrenergic amines, or any component of the formulation; need for acute bronchodilation

Warnings/Precautions

Salmeterol is not meant to relieve acute asthmatic symptoms. Acute episodes should be treated with short-acting beta2 agonist. Optimize anti-inflammatory treatment before initiating maintenance treatment with salmeterol. Do not use as a component of chronic therapy without an anti-inflammatory agent. Patient must be instructed to seek medical attention in cases where acute symptoms are not relieved by short-acting beta-agonist ( salmeterol) or a previous level of response is diminished. Treatment must not be delayed.

Use caution in patients with cardiovascular disease (arrhythmia or hypertension or CHF), convulsive disorders, diabetes, glaucoma, hyperthyroidism, hepatic impairment, or hypokalemia. Beta agonists may cause elevation in blood pressure, heart rate, and result in CNS stimulation/excitation. Beta2 agonists may increase risk of arrhythmia, increase serum glucose, or decrease serum potassium.

In a large, randomized clinical trial (SMART), salmeterol was associated with a small, but statistically significant increase in asthma-related deaths (when added to usual asthma therapy); risk may be greater in African-American patients versus Caucasians.

Do not exceed recommended dose; serious adverse events including fatalities, have been associated with excessive use of inhaled sympathomimetics. Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. Safety and efficacy have not been established in children <4 years of age.

Adverse Reactions

>10%:

Central nervous system: Headache

Endocrine & metabolic: Serum glucose increased, serum potassium decreased

Respiratory: Pharyngitis

1% to 10%:

Cardiovascular: Tachycardia, palpitation, elevation or depression of blood pressure, cardiac arrhythmia

Central nervous system: Nervousness, CNS stimulation, hyperactivity, insomnia, malaise, dizziness

Gastrointestinal: GI upset, diarrhea, nausea

Neuromuscular & skeletal: Tremors (may be more common in the elderly), myalgia, back pain, arthralgia

Respiratory: Upper respiratory infection, cough, bronchitis

<1% (Limited to important or life-threatening): Hypokalemia; immediate hypersensitivity reactions (rash, urticaria, bronchospasm); paradoxical bronchospasms, laryngeal spasm, arrhythmia, atrial fibrillation

Postmarketing and/or case reports: Anaphylactic reaction in patients with severe milk protein allergy (very rare), hypertension, oropharyngeal irritation

Overdosage/Toxicology

Symptoms of overdose include tachycardia, tremor, hypertension, angina, and seizures. Hypokalemia also may occur. Cardiac arrest and death may be associated with abuse of beta-agonist bronchodilators. Treatment includes immediate discontinuation and symptomatic and supportive therapies. Cautious use of beta-adrenergic blocking agents may be considered in severe cases.

Drug Interactions

of CYP3A4 (major)

Beta-blockers (nonselective): May antagonize therapeutic effect of salmeterol.

MAO inhibitors: May increase toxicity of salmeterol. Wait 2 weeks after discontinuing MAO inhibitors before initiating salmeterol therapy.

Tricyclic antidepressants (TCAs): May increase toxicity of salmeterol. Wait 2 weeks after discontinuing TCA before initiating salmeterol therapy.

Stability

Inhalation powder: Store at controlled room temperature 20°C to 25°C (68°F to 77°F) in a dry place away from direct heat or sunlight. Stable for 6 weeks after removal from foil pouch.

Mechanism of Action

Relaxes bronchial smooth muscle by selective action on beta2-receptors with little effect on heart rate; because salmeterol acts locally in the lung, therapeutic effect is not predicted by plasma levels

Pharmacodynamics/Kinetics

Onset of action: Asthma: 30-48 minutes, COPD: 2 hours

Peak effect: 2-4 hours, COPD: 3.27-4.75 hours

Duration: 12 hours

Protein binding: 96%

Metabolism: Hepatically hydroxylated

Half-life elimination: 5.5 hours

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

Dosage

Inhalation, powder (Serevent® Diskus®):

Asthma, maintenance and prevention: Children

Exercise-induced asthma, prevention: Children

COPD (maintenance treatment of associated bronchospasm): Adults: One inhalation (50 mcg) twice daily (~12 hours apart)

Administration

Inhalation: to be used for the relief of acute attacks. Not for use with a spacer device. Administer with Diskus® in a level, horizontal position. Do not wash mouthpiece; Diskus® should be kept dry.

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.

Patient Education

Use exactly as directed (see Administration below). Do not use more often than recommended (excessive use may result in tolerance, overdose may result in serious adverse effects) and do not discontinue without consulting prescriber. Do not use for acute attacks. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience nervousness, dizziness, or fatigue (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or dry mouth, stomach upset (small, frequent meals, frequent mouth care, chewing gum, or sucking hard candy may help). If you have diabetes, check blood sugar; blood glucose level may be increased. Report unresolved GI upset; dizziness or fatigue; vision changes; chest pain, rapid heartbeat, or palpitations; insomnia; nervousness or hyperactivity; muscle cramping, tremors, or pain; unusual cough; or skin rash. Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Cardiovascular Considerations

Beta agonists will induce increases in heart rate. This should be considered in patients with resting tachycardia. Because of the frequent coexistence of chronic obstructive lung disease and coronary artery disease, many patients are on simultaneous therapy with beta agonists and beta-blockade. This combination should, for obvious reasons, be avoided. Frequent use of inhaled beta agonists when used in patients with atrial fibrillation, may counteract pharmacologic interventions directed at rate control. Acute inhaled beta agonists may be used to treat hyperkalemia in patients with renal failure.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause nervousness, dizziness, hyperactivity, or insomnia

Mental Health: Effects on Psychiatric Treatment

Salmeterol is a sympathomimetic; use MAO inhibitors and TCAs with caution

Dosage Forms

Powder for oral inhalation (Serevent® Diskus®): 50 mcg (28s, 60s) [delivers 46 mcg/inhalation; contains lactose]

References

Bone RC, "Another Word of Caution Regarding a new Long-Acting Bronchodilator,"JAMA, 1995, 273(12):967-8.

Brogden RN and Faulds D, "Salmeterol Xinafoate: A Review of Its Pharmacological Properties and Therapeutic Potential in Reversible Obstructive Airways Disease,"Drugs, 1991, 42(5):895-912.

Clark CE, Ferguson AD, and Siddorn JA, "Respiratory Arrests in Young Asthmatics on Salmeterol,"Respir Med, 1993, 87(3):227-8.

Devoy MA, Fuller RW, and Palmer JB, "Are There any Detrimental Effects of the Use of Inhaled Long-Acting Beta-2-Agonists in the Treatment of Asthma?"Chest, 1995, 107(4):1116-24.

Hatton MQ, Allen MB, Mellor EJ, et al, "Salmeterol Rash,"Lancet, 1991, 337(8750):1169-70.

Johnson M, "The Pharmacology of Salmeterol,"Lung, 1990, 168(Suppl):115-9.

Meyer JM, Wenzel CL, and Kradjan WA, "Salmeterol: A Novel, Long-Acting Beta2-Agonist,"Ann Pharmacother, 1993, 27(12):1478-87.

National Asthma Education and Prevention Program, "Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma," Bethesda, MD, National Institutes of Health, 1997. NIH publication 97-4051.

National Asthma Education and Prevention Program, "Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics - 2002,"J Allergy Clin Immunol, 2002, 110(5 Suppl):141-219.

International Brand Names

Abrilar® (AR); Arial® (IT); Astmerole Inhaler® (TR); Astmerole Maxihaler® (TR); Beglan® (ES); Betamican® (ES); Bexitrol® (BD); Dilamax® (PT); Kolpovent® (CL); Salmetedur® (IT); Salmeter® (BD, IN, RO, RU); Serevent® (AR, AT, AU, BE, BG, BR, CA, CH, CL, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, HR, HU, ID, IE, IT, KW, LU, MX, NL, NO, NZ, PA, PL, PT, RO, SE, SG, SI, SV, TH, TR, YU); Serevent Diskus® (AR, AT, FR, HU, IL, SE); Serevent Dysk® (PL); Serevent Rotadisk® (PL); Serevent Rotadisks® (HU); Serobid® (IN); Ultrabeta® (PT); Veraspir® (PT)