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COPD: Nebulization: 15 mcg twice daily; maximum: 30 mcg/day Dosing: Geriatric Refer to adult dosing. Dosing: Renal Impairment No adjustment required. Dosing: Hepatic Impairment No dosage adjustment required, but use caution; systemic drug exposure prolonged (1.3- to 2.4-fold). Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Solution, for nebulization: Brovana®: 15 mcg/2 mL (30s, 60s) Generic Equivalent Available: U.S. No Medication Guide An FDA-approved patient medication guide, which is available with the product information and at file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088566.pdf , must be dispensed with this medication. Administration Nebulization: Remove each vial from individually sealed foil pouch immediately before use. Use with standard jet nebulizer connected to an air compressor, administer with mouthpiece or face mask. Administer vial undiluted and do not mix with other medications in nebulizer. Use Long-term maintenance treatment of bronchoconstriction in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema Adverse Reactions Significant 2% to 10%: Cardiovascular: Chest pain (7%), peripheral edema (3%) Central nervous system: Pain (8%) Dermatologic: Rash (4%) Gastrointestinal: Diarrhea (6%) Neuromuscular & skeletal: Back pain (6%), leg cramps (4%) Respiratory: Dyspnea (4%), sinusitis (5%), congestive conditions (2%) Miscellaneous: Flu-like syndrome (3%)

Adverse Reactions Significant 2% to 10%: Cardiovascular: Chest pain (7%), peripheral edema (3%) Central nervous system: Pain (8%) Dermatologic: Rash (4%) Gastrointestinal: Diarrhea (6%) Neuromuscular & skeletal: Back pain (6%), leg cramps (4%) Respiratory: Dyspnea (4%), sinusitis (5%), congestive conditions (2%) Miscellaneous: Flu-like syndrome (3%) <2% (Limited to important or life-threatening): Abscess, agitation, allergic reaction, arteriosclerosis, arthralgia, arthritis, atrial flutter, AV block, bone disorder, calcium crystalluria, cystitis, cerebral infarct, CHF, circumoral paresthesia, constipation, dehydration, digitalis intoxication, dry skin, ECG changes, edema, fever, gastritis, glaucoma, glucose tolerance decreased, glycosuria, gout, heart block, hematuria, hernia, hyper-/hypoglycemia, hyperlipemia, hypokalemia, hypokinesia, inverted T-wave, kidney calculus, lung carcinoma, melena, MI, neck rigidity, neoplasm, nocturia, oral moniliasis, paradoxical bronchospasm, paralysis, pelvic pain, periodontal abscess, PSA increased, pyuria, QT interval increased, rectal hemorrhage, retroperitoneal hemorrhage, rheumatoid arthritis, skin discoloration, skin hypertrophy, somnolence, supraventricular tachycardia, tendinous contracture, tremor, urinary tract disorder, urine abnormality, viral infection, vision abnormalities, voice alteration Contraindications Hypersensitivity to arformoterol, racemic formoterol, or any component of the formulation Additional contraindication for all long-acting beta 2 -agonists: Use in patients with asthma (without concomitant use of a long-term asthma control medication) Warnings/Precautions

Concerns related to adverse effects: • Asthma-related deaths: [U.S. Boxed Warning]: Long-acting beta 2 -agonists (LABAs) increase the risk of asthma-related deaths. 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. LABAs should not be used for acute bronchospasm. Safety and efficacy of arformoterol in patients with asthma have not been established. • Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. • Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported. • Serious effects/fatalities: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

Disease-related concerns: • Cardiovascular disease: Use with caution in patients with cardiovascular disease (eg, arrhythmia, hypertension, HF); beta-agonists may cause elevation in blood pressure, heart rate and result in CNS stimulation/excitation. Beta 2 -agonists may also increase risk of arrhythmias and prolong QT c interval. • 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. • Diabetes: Use with caution in patients with diabetes mellitus; beta 2 -agonists may increase serum glucose. • Hepatic impairment: Use with caution in patients with hepatic impairment; systemic clearance prolonged in hepatic dysfunction. • Hyperthyroidism: Use with caution in patients with hyperthyroidism; may stimulate thyroid activity. • Hypokalemia: Use with caution in patients with hypokalemia; beta 2 -agonists may decrease serum potassium. • Seizure disorders: Use with caution in patients with seizure disorders; beta 2 -agonists may result in CNS stimulation/excitation.

Other warnings/precautions: • Patient information: Patients using inhaled, short-acting beta 2 -agonists (eg, albuterol) should be instructed to discontinue routine use of these medications prior to beginning treatment; short-acting agents should be reserved for symptomatic relief of acute symptoms. Patients must be instructed 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 short-acting beta 2 -agonists may indicate deterioration of COPD, and medical evaluation must not be delayed. • Tolerance/Tachyphylaxis: Tolerance to the bronchodilator effect, measured by FEV 1 , has been observed in studies. Metabolism/Transport Effects None known. Drug Interactions (For additional information: Launch Lexi-Interact™ Drug Interactions Program ) Alpha-/Beta-Blockers: May diminish the therapeutic effect of Beta2-Agonists. Risk D: Consider therapy modification AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Risk C: 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. Risk C: 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. Risk C: Monitor therapy Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Risk C: Monitor therapy Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy MAO Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy Thiazide Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy Thiazide Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy Pregnancy Risk Factor C ( show table ) Pregnancy Implications Teratogenic effects, decreased fetal weight and increased fetal loss were observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Beta-agonists may interfere with uterine contractility if administered during labor. Use in pregnancy and/or during labor should be limited to situations where benefit outweighs risk to fetus. Lactation Excretion in breast milk unknown/use caution Pricing: U.S. (Medi-Span®)

Nebulization (Brovana Inhalation) 15 mcg/2 mL (2 mL): $8.75 Monitoring Parameters FEV 1 , 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 beta 2 -agonist inhalers; may be marker of a deteriorating COPD condition. Mechanism of Action Arformoterol, the (R,R)-enantiomer of the racemic formoterol, is a long-acting beta 2 -agonist that relaxes bronchial smooth muscle by selective action on beta 2 -receptors with little effect on cardiovascular system. Pharmacodynamics/Kinetics Onset of action: 7-20 minutes Peak effect: 1-3 hours Absorption: A portion of inhaled dose is absorbed into systemic circulation Protein binding: 52% to 65% Metabolism: Hepatic via direct glucuronidation and secondarily via O-demethylation; CYP2D6 and CYP2C19 (to a lesser extent) involved in O-demethylation Half-life elimination: 26 hours Time to peak: 0.5-3 hours Use of UpToDate is subject to the Subscription and License Agreement . Topic 9433 Version 34.0 © 2013 UpToDate, Inc. All rights reserved. | Subscription and License Agreement | Release: 21.4 - C21.36 Licensed to: Southeast Alabama Med Ctr | Support Tag: [0504-125.39.66.147-AA4CF5E739-S244013.14]