Arformoterol Tartrate

Bronchodilator; relatively selective long-acting β2-agonist.1 2 3 12 13

Contraindications

Known hypersensitivity to arformoterol, formoterol, or any ingredient in formulation.1

All long-acting β2-adrenergic agonists, including arformoterol, contraindicated in patients with asthma without concomitant use of long-term asthma controller therapy; safety and efficacy of arformoterol in patients with asthma† not established.1 (See Asthma-related Death under Cautions.)

Warnings/Precautions

Warnings

Increased risk of asthma-related death reported with long-acting β2-adrenergic agonists.1 (See REMS and also see Boxed Warning.)

All long-acting β2-adrenergic agonists, including arformoterol, contraindicated in patients with asthma without concomitant use of long-term asthma controller therapy.1 Safety and efficacy of arformoterol in patients with asthma† not established.1

Data from large placebo-controlled safety study (Salmeterol Multicenter Asthma Research Trial [SMART]) showed an increase in asthma-related deaths in patients receiving salmeterol in addition to usual asthma therapy,1 14 15 16 17 which is considered class effect of long-acting β2-adrenergic agonists, including arformoterol.1 However, no adequate studies conducted to determine whether rate of asthma-related death is increased in patients receiving arformoterol.1 (See Advice to Patients.)

While data from currently available studies do not show increased risk of asthma-related death with racemic formoterol, data from small clinical studies suggest higher incidence of serious asthma exacerbations with formoterol compared with placebo.1 7

Not known whether rate of death is increased in patients with COPD receiving arformoterol.1 2 7 Data from large placebo-controlled study (TOwards a Revolution in COPD Health [TORCH]) evaluating survival in patients with COPD receiving salmeterol, fluticasone propionate, or both drugs over a 3-year period did not reveal an increased incidence of COPD-related or overall deaths in patients receiving salmeterol in addition to usual COPD therapy.22 23

Do not initiate therapy in patients with acutely deteriorating COPD, which may be life threatening;1 not indicated for treatment of acute episodes of bronchospasm (i.e., rescue therapy).1 6 Safety and efficacy of arformoterol for relief of acute symptoms of COPD not established.1 6

Failure to respond to a previously effective dosage of arformoterol or supplemental short-acting β2-agonist (e.g., increased need for additional short-acting β2-agonist) may indicate substantially worsening COPD.1 6 Promptly reevaluate COPD therapy.1 6 Do not use extra doses of arformoterol alone or with other long-acting, inhaled β2-adrenergic agonists (e.g., formoterol) for maintenance therapy of COPD or any other reason.1 2 6 7

Possible clinically important changes in systolic and/or diastolic BP, heart rate, ECG (e.g., flattening of T wave, prolongation of QTc interval, ST-segment depression) changes, and/or cardiovascular symptoms.1 3 6 13 Such effects uncommon with recommended dosage; may require discontinuance of drug.1 6

Use with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, or hypertension.1 6

Fatalities associated with excessive use of inhaled sympathomimetic drugs.1 6 Do not use higher than recommended dosage of arformoterol.1 6

Patients receiving arformoterol should not use additional arformoterol or other long-acting β2-adrenergic agonists for maintenance treatment of COPD.1 2 6

Sensitivity Reactions

Immediate hypersensitivity reactions (e.g., anaphylactic reactions, urticaria, angioedema, rash, bronchospasm) reported.1 6

Major Toxicities

Possible acute, life-threatening, paradoxical bronchospasm may occur.1 6

Discontinue therapy immediately if bronchospasm occurs and institute alternative therapy.1 6

General Precautions

Possible hypokalemia; may increase risk of adverse cardiovascular effects.1 3 6 9 11 Hypokalemia usually transient, not requiring supplementation.1

Clinically important changes in blood glucose concentrations possible during long-term therapy at recommended dosage.1 3 6

Use with caution in patients with thyrotoxicosis.1 6

Use with caution in patients with seizure disorders and those unusually responsive to sympathomimetic amines.1 6

Specific Populations

Category C.1

Distributed into milk in rats.1 Not known whether distributed into human milk.1 Use caution.1

Safety and efficacy not established.1 COPD does not occur in children.1

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 Incidence of ventricular ectopy in geriatric patients 65–75 years of age with arformoterol comparable to that with placebo.1

Because plasma concentrations of arformoterol may be increased in patients with hepatic impairment, use with caution and monitor patients closely.1 (See Absorption under Pharmacokinetics.)

Common Adverse Effects

Pain (unspecified),1 chest pain,1 back pain,1 diarrhea,1 sinusitis,1 leg cramps,1 dyspnea,1 rash,1 flu syndrome,1 peripheral edema,1 lung disorder.1

Minimally metabolized by CYP2D6 and CYP2C19 isoenzymes;1 does not inhibit CYP isoenzymes 1A2, 2A6, 2C9/10, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.1 6

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6: Pharmacokinetic interaction unlikely; dosage adjustment not required.1

Drugs that Prolong QT Interval

Potential pharmacodynamic interaction (increased risk of ventricular arrhythmias).1 Use concomitantly with extreme caution.1 13

Specific Drugs

Storage

Oral Inhalation Solution

2–8°C.1 Store single-use vials in protective foil pouch to protect from light until used.1 Unopened foil pouches may be kept at 20–25°C for ≤6 weeks.1 Discard such unopened foil pouches after >6 weeks or after manufacturer’s labeled expiration date (whichever comes first).1

Once foil pouch has been opened, use immediately.1 Discard vial if solution discolored.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

For information on systemic interactions resulting from concomitant use, see Interactions.

Compatible with ipratropium bromide, acetylcysteine, or budesonide oral inhalation solution when admixed extemporaneously.21 22

• Arformoterol is the active R, R-enantiomer of racemic formoterol.1 3 6 12 Arformoterol is twice as potent as racemic formoterol.12 13

• Stimulates β2-adrenergic receptors and apparently has little or no effect on β1-adrenergic or muscarinic receptors.1 4 7 8

• Stimulates production of cyclic adenosine-3′, 5′-monophosphate (cAMP), which mediates numerous cellular responses, including bronchial smooth muscle relaxation and inhibition of release of proinflammatory mediators (e.g., histamine, leukotrienes) from mast cells in airways.1 5 8 11 12 13

• Inhibits allergen-induced infiltration of eosinophils into airways and histamine-induced extravasation of plasma proteins (e.g., albumin) in animal models.1

• Long-term maintenance therapy (e.g., >6 weeks) associated with development of tolerance to bronchodilatory effects as evidenced by some decrease in FEV1 at the end of the dosing interval.1 13 22