Arformoterol Tartrate
Solution · Respiratory (inhalation)
Uses
Arformoterol tartrate inhalation solution is a long-acting beta 2 -adrenergic agonist (beta 2 -agonist) indicated for: Long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. (1.1) Important limitations of use: Arformoterol tartrate inhalation solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. (1.2, 5.2) Arformoterol tartrate inhalation solution is not indicated to treat asthma. (1.2) 1.1 Maintenance Treatment of COPD Arformoterol tartrate inhalation solution is indicated for the long-term, twice daily (morning and evening) maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Arformoterol tartrate inhalation solution is for use by nebulization only. 1.2 Important Limitations of Use Arformoterol tartrate inhalation solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease [see Warnings and Precautions (5.2)]. Arformoterol tartrate inhalation solution is not indicated to treat asthma. The safety and effectiveness of arformoterol tartrate inhalation solution in asthma have not been established.
Dosage and administration
The recommended dose of arformoterol tartrate inhalation solution is one 15 mcg unit-dose vial administered twice daily (morning and evening) by nebulization. A total daily dose of greater than 30 mcg (15 mcg twice daily) is not recommended. Arformoterol tartrate inhalation solution should be administered by the orally inhaled route via a standard jet nebulizer connected to an air compressor (see the accompanying Patient Information ). Arformoterol tartrate inhalation solution should not be swallowed. Arformoterol tartrate inhalation solution should be stored refrigerated in foil pouches. After opening the pouch, unused unit-dose vials should be returned to, and stored in, the pouch. An opened unit-dose vial should be used right away. If the recommended maintenance treatment regimen fails to provide the usual response, medical advice should be sought immediately, as this is often a sign of destabilization of COPD. Under these circumstances, the therapeutic regimen should be reevaluated and additional therapeutic options should be considered. No dose adjustment is required for patients with renal or hepatic impairment. However, since the clearance of arformoterol tartrate inhalation solution is prolonged in patients with hepatic impairment, they should be monitored closely. The drug compatibility (physical and chemical), efficacy, and safety of arformoterol tartrate inhalation solution when mixed with other drugs in a nebulizer have not been established. The safety and efficacy of arformoterol tartrate inhalation solution have been established in clinical trials when administered using the PARI LC® Plus nebulizer (with a face mask or mouthpiece) and the PARI DURA NEB™ 3000 compressor. The safety and efficacy of arformoterol tartrate inhalation solution delivered from non-compressor based nebulizer systems have not been established. For oral inhalation only. A total daily dose of greater than 30 mcg is not recommended. (2) One 15 mcg/2 mL vial every 12 hours. (2) For use with a standard jet nebulizer (with a face mask or mouthpiece) connected to an air compressor. (2)
Dosage forms and strengths
Arformoterol tartrate inhalation solution is supplied as a sterile solution for nebulization in low-density polyethylene unit-dose vials. Each 2 mL vial contains 15 mcg of arformoterol equivalent to 22 mcg of arformoterol tartrate. Inhalation Solution (unit-dose vial for nebulization): 15 mcg/2 mL solution (3)
Contraindications
Arformoterol tartrate inhalation solution is contraindicated in patients with a history of hypersensitivity to arformoterol, racemic formoterol or to any other components of this product. Use of a LABA, including arformoterol tartrate inhalation solution, without an inhaled cortisteroid is contraindicated in patients with asthma [see Warnings and Precautions (5)]. Arformoterol tartrate inhalation solution is not indicated for the treatment of asthma. Arformoterol tartrate inhalation solution is contraindicated in patients with a history of hypersensitivity to arformoterol, racemic formoterol or to any other components of this product. (4) Use of a LABA, including arformoterol tartrate inhalation solution, without an inhaled corticosteroid is contraindicated in patients with asthma. (4)
Warnings and precautions
5 WARNINGS AND PRECAUTIONS LABA as monotherapy (without an inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. (5.1) Do not initiate arformoterol tartrate inhalation solution in acutely deteriorating patients. (5.2) Do not use for relief of acute symptoms. Concomitant short-acting beta2- agonists can be used as needed for acute relief. (5.2) Do not exceed the recommended dose. Excessive use of arformoterol tartrate inhalation solution, or use in conjunction with other medications containing long-acting beta2-agonists, can result in clinically significant cardiovascular effects, and may be fatal. (5.3, 5.5) Life-threatening paradoxical bronchospasm can occur. Discontinue arformoterol tartrate inhalation solution immediately. (5.4) Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. (5.6, 5.7) 5.1 Serious Asthma-Related Events - Hospitalizations, Intubations Deaths The safety and efficacy of arformoterol tartrate inhalation solution in patients with asthma have not been established. Arformoterol tartrate inhalation solution is not indicated for the treatment of asthma [see Contraindications (4)]. Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, and death) compared with ICS alone. A 28-week, placebo-controlled US study comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs. 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). The increased risk of asthma-related death is considered a class effect of the LABA, including arformoterol tartrate inhalation solution. No study adequate to determine whether the rate of asthma-related death is increased in patients treated with arformoterol tartrate inhalation solution has been conducted. Clinical studies with racemic formoterol suggested a higher incidence of serious asthma exacerbations in patients who received racemic formoterol than in those who received placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups. Available data do not suggest an increased risk of death with use of LABA in patients with COPD. 5.2 Deterioration of Disease and Acute Episodes Arformoterol tartrate inhalation solution should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. The use of arformoterol tartrate inhalation solution in this setting is inappropriate. Arformoterol tartrate inhalation solution is not indicated for the treatment of acute episodes of bronchospasm, i.e., as rescue therapy and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled short-acting beta 2 -agonist. When beginning arformoterol tartrate inhalation solution, patients who have been taking inhaled short-acting beta 2 -agonists on a regular basis (e.g., four times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute respiratory symptoms. When prescribing arformoterol tartrate inhalation solution, the healthcare provider should also prescribe an inhaled, short-acting beta 2 -agonist and instruct the patient how it should be used. Increasing inhaled beta 2 -agonist use is a signal of deteriorating disease for which prompt medical attention is indicated. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If arformoterol tartrate inhalation solution no longer controls the symptoms of bronchoconstriction, or the patient’s inhaled, short-acting beta 2 -agonist becomes less effective or the patient needs more inhalation of short-acting beta 2 -agonist than usual, these may be markers of deterioration of disease. In this setting, a reevaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dosage of arformoterol tartrate inhalation solution beyond the recommended 15 mcg twice daily dose is not appropriate in this situation. 5.3 Excessive Use of Arformoterol Tartrate Inhalation Solution and Use with Other Long-Acting Beta2-Agonists Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. As with other inhaled beta 2 -adrenergic drugs, arformoterol tartrate inhalation solution should not be used more often, at higher doses than recommended, or in conjunction with other medications containing long-acting beta 2 -agonists. 5.4 Paradoxical Bronchospasm As with other inhaled beta 2 -agonists, arformoterol tartrate inhalation solution can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, arformoterol tartrate inhalation solution should be discontinued immediately and alternative therapy instituted. 5.5 Cardiovascular Effects Arformoterol tartrate inhalation solution, like other beta 2 -agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic and/or diastolic blood pressure, and/or symptoms. If such effects occur, the drug may need to be discontinued.
Side effects
Long-acting beta 2 -adrenergic agonists, such as arformoterol tartrate, as monotherapy (without inhaled corticosteroids) for asthma increase the risk of asthma-related events. Arformoterol tartrate inhalation solution is not indicated for the treatment of asthma [see Warnings and Precautions (5.1)]. Most common adverse reactions (≥2% incidence and more common than placebo) are pain, chest pain, back pain, diarrhea, sinusitis, leg cramps, dyspnea, rash, flu syndrome, peripheral edema and lung disorder. (6.2) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Beta 2 -Agonist Adverse Reaction Profile Adverse reactions to arformoterol tartrate inhalation solution are expected to be similar in nature to other beta 2 -adrenergic receptor agonists including: angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia. 6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults with COPD in Short-Term Trials (12 weeks) The safety data described below for adults ≥35 years of age are based on 2 clinical trials of 12 weeks. In the 2 trials of 12 weeks duration, 1456 patients (860 males and 596 females, ages 34 to 89 years old) with COPD were treated with arformoterol tartrate inhalation solution 15 mcg twice daily, 25 mcg twice daily, 50 mcg once daily, salmeterol 42 mcg twice daily, or placebo. The racial/ethnic distribution in these two trials included 1383 Caucasians, 49 Blacks, 10 Asians, and 10 Hispanics, and 4 patients classified as Other. Among the 1,456 COPD patients in two 12-week, placebo-controlled trials, 288 were treated with arformoterol tartrate inhalation solution 15 mcg twice daily and 293 were treated with placebo. Doses of 25 mcg twice daily and 50 mcg once daily were also evaluated. Table 1 shows adverse reaction rates among patients from these two trials where the frequency was greater than or equal to 2% in the arformoterol tartrate inhalation solution 15 mcg twice daily group and where the rate in the arformoterol tartrate inhalation solution 15 mcg twice daily group exceeded the rate in the placebo group. The total number and percent of patients who reported adverse events were 202 (70%) in the 15 mcg twice daily and 219 (75%) in the placebo groups. Ten adverse events demonstrated a dose relationship: asthenia, fever, bronchitis, COPD, headache, vomiting, hyperkalemia, leukocytosis, nervousness, and tremor. T able 1: Number of Patients Experiencing Adverse Events from Two 12-Week, Double-Blind, Placebo-Controlled Clinical Trials Total Patients Arformoterol Tartrate Inhalation Solution 15 mcg twice daily Placebo n (%) n (%) 288 (100) 293 (100) Pain 23 (8) 16 (5) Chest Pain 19 (7) 19 (6) Back Pain 16 (6) 6 (2) Diarrhea 16 (6) 13 (4) Sinusitis 13 (5) 11 (4) Leg Cramps 12 (4) 6 (2) Dyspnea 11 (4) 7 (2) Rash 11 (4) 5 (2) Flu Syndrome 10 (3) 4 (1) Peripheral Edema 8 (3) 7 (2) Lung Disorder* 7 (2) 2 (1) * Reported terms coded to “Lung Disorder” were predominantly pulmonary or chest congestion. Adverse events occurring in patients treated with arformoterol tartrate inhalation solution 15 mcg twice daily with a frequency of <2%, but greater than placebo, were as follows: Body as a Whole: abscess, allergic reaction, digitalis intoxication, fever, hernia, injection site pain, neck rigidity, neoplasm, pelvic pain, retroperitoneal hemorrhage Cardiovascular : arteriosclerosis, atrial flutter, AV block, congestive heart failure, heart block, myocardial infarct, QT interval prolonged, supraventricular tachycardia, inverted T-wave Digestive: constipation, gastritis, melena, oral moniliasis, periodontal abscess, rectal hemorrhage Metabolic and Nutritional Disorders: dehydration, edema, glucose tolerance decreased, gout, hyperglycemia, hyperlipemia, hypoglycemia, hypokalemia Musculoskeletal: arthralgia, arthritis, bone disorder, rheumatoid arthritis, tendinous contracture Nervous: agitation, cerebral infarct, circumoral paresthesia, hypokinesia, paralysis, somnolence, tremor Respiratory: carcinoma of the lung, respiratory disorder, voice alteration Skin and Appendages: dry skin, herpes simplex, herpes zoster, skin discoloration, skin hypertrophy Special Senses: abnormal vision, glaucoma Urogenital: breast neoplasm, calcium crystalluria, cystitis, glycosuria, hematuria, kidney calculus, nocturia, PSA increase, pyuria, urinary tract disorder, urine abnormality. In these trials, the overall frequency of all cardiovascular adverse events was 6.9% in arformoterol tartrate inhalation solution 15 mcg twice daily and 13.3% in the placebo group. There were no frequently occurring specific cardiovascular adverse events for arformoterol tartrate inhalation solution (frequency ≥1% and greater than placebo). The rate of COPD exacerbations was also comparable between the arformoterol tartrate inhalation solution 15 mcg twice daily and placebo groups, 12.2% and 15.1%, respectively. Adults with COPD in Long-Term (52-week) Safety Trial Arformoterol tartrate inhalation solution was evaluated in one 52 week double-blind, randomized, placebo-controlled, safety trial conducted in patients with moderate to severe COPD. The primary endpoint was time to either respiratory death or first COPD exacerbation-related hospitalization, whichever occurred first. The event had to be a death or hospitalization for which the patient’s respiratory status was predominant and/or inciting contributor, as determined by the clinical investigator.
Drug interactions
Other adrenergic drugs may potentiate effect. Use with caution. (5.3, 7.1) Xanthine derivatives, steroids, diuretics, or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. Use with caution. (5.7, 7.2, 7.3) MAO inhibitors, tricyclic antidepressants and drugs that prolong the QTc interval may potentiate effect on the cardiovascular system. Use with extreme caution. (7.4) Beta-blockers may decrease effectiveness. May block bronchodilatory effects of beta-agonists. Use with caution and only when medically necessary. (7.5) 7.1 Adrenergic Drugs If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of arformoterol may be potentiated [see Warnings and Precautions (5.3, 5.5, 5.6, 5.7)] . 7.2 Xanthine Derivatives, Steroids or Diuretics Concomitant treatment with methylxanthine (aminophylline, theophylline), steroids, or diuretics may potentiate any hypokalemic effect of adrenergic agonists including arformoterol tartrate inhalation solution [see Warnings and Precautions (5.7)]. The concurrent use of intravenously or orally administered methylxanthines (e.g., aminophylline, theophylline) by patients receiving arformoterol tartrate inhalation solution has not been completely evaluated. In two combined 12-week, placebo-controlled trials that included arformoterol tartrate inhalation solution doses of 15 mcg twice daily, 25 mcg twice daily, and 50 mcg once daily, 54 of 873 arformoterol tartrate inhalation solution-treated subjects received concomitant theophylline at study entry. In a 12-month controlled trial that included a 50 mcg once daily arformoterol tartrate inhalation solution dose, 30 of the 528 arformoterol tartrate inhalation solution-treated subjects received concomitant theophylline at study entry. In these trials, heart rate and systolic blood pressure were approximately 2 to 3 bpm and 6 to 8 mm Hg higher, respectively, in subjects on concomitant theophylline compared with the overall population. 7.3 Non-potassium Sparing Diuretics The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists, including arformoterol tartrate inhalation solution, with non-potassium sparing diuretics. 7.4 MAO Inhibitors, Tricyclic Antidepressants, QTc Prolonging Drugs Arformoterol tartrate inhalation solution, as with other beta-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval because of the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QT c interval have an increased risk of ventricular arrhythmias. 7.5 Beta-Blockers Beta-adrenergic receptor antagonists (beta-blockers) and arformoterol tartrate inhalation solution may inhibit the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
Use in specific populations
Hepatic Impairment Use with caution in patients with hepatic impairment. (8.6) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. Arformoterol tartrate should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the fetus. Women should be advised to contact their physician if they become pregnant while taking arformoterol tartrate. In animal reproduction studies with arformoterol administered by the oral route to rats and rabbits at exposures approximately 370 and 8,400 times the adult exposure at the maximum recommended human daily inhalation dose (MRHDID) of 15 mcg every 12 hours, respectively, there were findings of structural abnormalities, embryofetal and infant mortality, and alterations of growth. These adverse effects generally occurred at large multiples of the MRHDID when arformoterol was administered by the oral route to achieve high systemic exposures. No evidence of fetal harm was observed in rabbits at an exposure approximately 4,900 times the MRHDID. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Labor or Delivery: The potential effect of arformoterol tartrate on labor and delivery is unknown. Because of the potential for beta-agonists interference with uterine contractility, use of arformoterol tartrate inhalation solution during labor should be restricted to whom the benefits clearly outweigh the risk. Data Animal Data In an embryofetal development study in which pregnant rats received doses of 1,000, 5,000 or 10,000 mcg/kg/day from gestation days 6 to 17, arformoterol was shown to be teratogenic based upon findings of omphalocele (umbilical hernia), a malformation, in rat fetuses at exposures approximately 370 times adult exposure at the MRHDID (on an AUC basis with maternal oral doses of 1,000 mcg/kg/day and higher. Maternal toxicity was not observed in rats with exposures up to 2,400 times the MRHDID (on an AUC basis with maternal oral doses up to 10,000 mcg/kg/day). A no-observed-adverse-effect-level (NOAEL) for rat fetuses was not identified. In an embryofetal development study in which pregnant rabbits received doses of 20,000, 40,000 or 80,000 mcg/kg/day from gestation days 7 to 20, arformoterol was shown to be teratogenic based upon findings of malpositioned right kidney, a malformation, in rabbit fetuses at exposures approximately 8400 times and higher than the adult exposure at the MRHDID (on an AUC basis with maternal oral doses of 20,000 mcg/kg/day and higher). Malformations including brachydactyly, bulbous aorta, and liver cysts as well as decreased body weights were observed in rabbit fetuses at doses approximately 26,000 times and higher than the MRHDID in adults (on a mcg/m 2 basis with maternal oral doses of 40,000 mcg/kg/day and higher). Malformations including adactyly, lobular dysgenesis of the lung, and interventricular septal defect as well as embryolethality were observed in rabbit fetuses at a dose approximately 52,000 times the MRHDID in adults (on a mcg/m 2 basis with a maternal oral dose of 80,000 mcg/kg/day). Maternal toxicity was observed at doses approximately 26,000 times and higher than the MRHDID in adults (on a mcg/m 2 basis with maternal oral doses of 40,000 mcg/kg/day and higher). There was no evidence of fetal harm in rabbits at exposures approximately 4,900 times and lower than the adult exposure at the MRHDID (on an AUC basis with maternal oral doses of 10,000 mcg/kg/day and lower). In a pre- and post-natal development study, female rats received arformoterol at oral doses of 0, 1,000, 5,000, and 10,000 mcg/kg/day from gestation day 6 through lactation day 20. Lengths of gestation for female rats receiving doses 325 times and higher than the MRHDID (on a mcg/m 2 basis with maternal oral doses of 1,000 mcg/kg/day and higher) were slightly prolonged, which was attributed to prolonged parturition or dystocia due to the pharmacological action of β-adrenergic agonists such as arformoterol to relax uterine musculature. One female that had received a dose 3,200 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day) was euthanized due to complications during parturition. Pup survival and body weights were decreased at doses 1,600 times and higher than the MRHDID (on a mcg/m 2 basis with maternal oral doses of 5,000 mcg/kg/day and higher) at birth and during lactation. Umbilical hernia, a malformation, was observed for 1 pup at a dose 3,200 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day). Potential developmental delays of rat pups were observed at a dose 3,200 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day); however, no developmental delays were evident with doses 1,600 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 5,000 mcg/kg/day). 8.2 Lactation Risk Summary There are no data on the presence of arformoterol or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. However, arformoterol was excreted in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for arformoterol tartrate and any potential adverse effects on the breastfed infant from arformoterol tartrate or from the underlying maternal condition. Data Arformoterol and its metabolites were detected in the milk of lactating rats following oral administration of a 10,000 mcg/kg dose of radiolabeled arformoterol tartrate.
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. Arformoterol tartrate should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the fetus. Women should be advised to contact their physician if they become pregnant while taking arformoterol tartrate. In animal reproduction studies with arformoterol administered by the oral route to rats and rabbits at exposures approximately 370 and 8,400 times the adult exposure at the maximum recommended human daily inhalation dose (MRHDID) of 15 mcg every 12 hours, respectively, there were findings of structural abnormalities, embryofetal and infant mortality, and alterations of growth. These adverse effects generally occurred at large multiples of the MRHDID when arformoterol was administered by the oral route to achieve high systemic exposures. No evidence of fetal harm was observed in rabbits at an exposure approximately 4,900 times the MRHDID. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Labor or Delivery: The potential effect of arformoterol tartrate on labor and delivery is unknown. Because of the potential for beta-agonists interference with uterine contractility, use of arformoterol tartrate inhalation solution during labor should be restricted to whom the benefits clearly outweigh the risk. Data Animal Data In an embryofetal development study in which pregnant rats received doses of 1,000, 5,000 or 10,000 mcg/kg/day from gestation days 6 to 17, arformoterol was shown to be teratogenic based upon findings of omphalocele (umbilical hernia), a malformation, in rat fetuses at exposures approximately 370 times adult exposure at the MRHDID (on an AUC basis with maternal oral doses of 1,000 mcg/kg/day and higher. Maternal toxicity was not observed in rats with exposures up to 2,400 times the MRHDID (on an AUC basis with maternal oral doses up to 10,000 mcg/kg/day). A no-observed-adverse-effect-level (NOAEL) for rat fetuses was not identified. In an embryofetal development study in which pregnant rabbits received doses of 20,000, 40,000 or 80,000 mcg/kg/day from gestation days 7 to 20, arformoterol was shown to be teratogenic based upon findings of malpositioned right kidney, a malformation, in rabbit fetuses at exposures approximately 8400 times and higher than the adult exposure at the MRHDID (on an AUC basis with maternal oral doses of 20,000 mcg/kg/day and higher). Malformations including brachydactyly, bulbous aorta, and liver cysts as well as decreased body weights were observed in rabbit fetuses at doses approximately 26,000 times and higher than the MRHDID in adults (on a mcg/m 2 basis with maternal oral doses of 40,000 mcg/kg/day and higher). Malformations including adactyly, lobular dysgenesis of the lung, and interventricular septal defect as well as embryolethality were observed in rabbit fetuses at a dose approximately 52,000 times the MRHDID in adults (on a mcg/m 2 basis with a maternal oral dose of 80,000 mcg/kg/day). Maternal toxicity was observed at doses approximately 26,000 times and higher than the MRHDID in adults (on a mcg/m 2 basis with maternal oral doses of 40,000 mcg/kg/day and higher). There was no evidence of fetal harm in rabbits at exposures approximately 4,900 times and lower than the adult exposure at the MRHDID (on an AUC basis with maternal oral doses of 10,000 mcg/kg/day and lower). In a pre- and post-natal development study, female rats received arformoterol at oral doses of 0, 1,000, 5,000, and 10,000 mcg/kg/day from gestation day 6 through lactation day 20. Lengths of gestation for female rats receiving doses 325 times and higher than the MRHDID (on a mcg/m 2 basis with maternal oral doses of 1,000 mcg/kg/day and higher) were slightly prolonged, which was attributed to prolonged parturition or dystocia due to the pharmacological action of β-adrenergic agonists such as arformoterol to relax uterine musculature. One female that had received a dose 3,200 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day) was euthanized due to complications during parturition. Pup survival and body weights were decreased at doses 1,600 times and higher than the MRHDID (on a mcg/m 2 basis with maternal oral doses of 5,000 mcg/kg/day and higher) at birth and during lactation. Umbilical hernia, a malformation, was observed for 1 pup at a dose 3,200 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day). Potential developmental delays of rat pups were observed at a dose 3,200 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day); however, no developmental delays were evident with doses 1,600 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 5,000 mcg/kg/day).
Pediatric use
8.4 Pediatric Use Arformoterol tartrate inhalation solution is approved for use in the long-term maintenance treatment of bronchoconstriction associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. This disease does not occur in children. The safety and efficacy of arformoterol tartrate inhalation solution in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Of the 873 patients who received arformoterol tartrate inhalation solution in two placebo-controlled clinical studies in adults with COPD, 391 (45%) were 65 years of age or older while 96 (11%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Among subjects age 65 years and older, 129 (33%) received arformoterol tartrate inhalation solution at the recommended dose of 15 mcg twice daily, while the remainder received higher doses. ECG alerts for ventricular ectopy in patients 65 to ≤75 years of age were comparable among patients receiving 15 mcg twice daily, 25 mcg twice daily, and placebo (3.9%, 5.2%, and 7.1%, respectively). A higher frequency (12.4%) was observed when arformoterol tartrate inhalation solution was dosed at 50 mcg once daily. The clinical significance of this finding is not known. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
The expected signs and symptoms associated with overdosage of arformoterol tartrate inhalation solution are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms listed under ADVERSE REACTIONS . Signs and symptoms may include angina, hypertension or hypotension, tachycardia, with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia. As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of arformoterol tartrate inhalation solution. Treatment of overdosage consists of discontinuation of arformoterol tartrate inhalation solution together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of arformoterol tartrate inhalation solution. Cardiac monitoring is recommended in cases of overdosage.
Description
Arformoterol tartrate inhalation solution is a sterile, clear, colorless, aqueous solution of the tartrate salt of arformoterol, the (R,R)-enantiomer of formoterol. Arformoterol is a selective beta 2 -adrenergic bronchodilator. The chemical name for arformoterol tartrate is formamide, N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]-,(2R,3R)-2,3-dihydroxy butanedioate (1:1 salt), and its established structural formula is as follows: The molecular weight of arf o rm o ter o l tartrate is 494.5 g/mol, and its molecular formula is C 19 H 2 4 N 2 O 4 . C 4 H 6 O 6 (1:1 salt). It is a white or off white or light brown colored powder that is slightly soluble in water. Arformoterol tartrate is the United States Adopted Name (USAN) for (R,R)-formoterol L-tartrate. Arformoterol tartrate inhalation solution is supplied as 2 mL of arformoterol tartrate solution packaged in 3 mL unit-dose, low-density polyethylene (LDPE) unit-dose vials. Each unit-dose vial contains 15 mcg of arformoterol (equivalent to 22 mcg of arformoterol tartrate) in a sterile, isotonic saline solution, pH-adjusted to 5.0 with citric acid and sodium citrate. Arformoterol tartrate inhalation solution requires no dilution before administration by nebulization. Like all other nebulized treatments, the amount delivered to the lungs will depend upon patient factors, the nebulizer used, and compressor performance. Using the PARI LC ® Plus nebulizer (with mouthpiece) connected to a PARI DURA NEB TM 3000 compressor under in vitro conditions, the mean delivered dose from the mouthpiece (% nominal) was approximately 4.1 mcg (27.6%) at a mean flow rate of 3.3 L/min. The mean nebulization time was 6 minutes or less. Arformoterol tartrate inhalation solution should be administered from a standard jet nebulizer at adequate flow rates via face mask or mouthpiece. Patients should be carefully instructed on the correct use of this drug product (please refer to the accompanying Patient Information ) . spl-arformoterol-chem-str
Mechanism of action
12.1 Mechanism of Action Arformoterol, the (R,R)-enantiomer of formoterol, is a selective long-acting beta 2 -adrenergic receptor agonist (beta 2 -agonist) that has two-fold greater potency than racemic formoterol (which contains both the (S,S) and (R,R)-enantiomers). The (S,S)-enantiomer is about 1,000-fold less potent as a beta 2 -agonist than the (R,R)-enantiomer. While it is recognized that beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, data indicate that there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects. The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including arformoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (cyclic AMP). Increased intracellular cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Arformoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown.
How supplied
Arformoterol tartrate inhalation solution is supplied in a single strength (15 mcg of arformoterol, equivalent to 22 mcg of arformoterol tartrate) as 2 mL of a sterile, clear, colorless aqueous solution in low-density polyethylene (LDPE) unit-dose vials overwrapped in foil. Arformoterol tartrate inhalation solution is available in a shelf-carton containing 30 or 60 unit-dose vials. NDC 62756-277-02: carton of 30 unit-dose vials (6x5 unit-dose vial pouches). NDC 62756-277-03: carton of 60 unit-dose vials (12x5 unit-dose vial pouches). Storage and Handling Store arformoterol tartrate inhalation solution in the protective foil pouch under refrigeration at 36° to 46°F (2° to 8°C). Protect from light and excessive heat. After opening the pouch, unused unit-dose vials should be returned to, and stored in, the pouch. An opened unit-dose vial should be used right away. Discard any unit-dose vial if the solution is not colorless. Unopened foil pouches of arformoterol tartrate inhalation solution can also be stored at room temperature 68° to 77°F (20° to 25°C) for up to 6 weeks. If stored at room temperature, discard if not used after 6 weeks or if past the expiration date, whichever is sooner. Discard unused portion.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use) with each new prescription and refill. The complete text of the Patient Information is reprinted at the end of this document. Patients should be given the following information: Serious Asthma-Related Events, Acute Exacerbations or Deteriorations Patients should be informed that long-acting beta 2 -adrenergic agonists, such as arformoterol tartrate inhalation solution, when used as monotherapy [without an inhaled corticosteroid], increase risk of serious asthma-related events, including asthma-related death. Arformoterol tartrate inhalation solution is not indicated for the treatment of asthma. Arformoterol tartrate inhalation solution is not indicated to relieve acute respiratory symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta 2 -agonist (the healthcare provider should prescribe the patient with such medication and instruct the patient in how it should be used). Patients should be instructed to seek medical attention if their symptoms worsen despite recommended doses of arformoterol tartrate inhalation solution, if arformoterol tartrate inhalation solution treatment becomes less effective, or if they need more inhalations of a short-acting beta 2 -agonist than usual. Appropriate Dosing Patients should not stop using arformoterol tartrate inhalation solution unless told to do so by a healthcare provider because symptoms may get worse. Patients should not inhale more than one dose at any one time. The daily dosage of arformoterol tartrate inhalation solution should not exceed one unit-dose vial (15 mcg) by inhalation twice daily (30 mcg total daily dose). Excessive use of sympathomimetics may cause significant cardiovascular effects, and may be fatal. Concomitant Therapy Patients who have been taking inhaled, short-acting beta 2 -agonists (e.g., levalbuterol) on a regular basis should be instructed to discontinue the regular use of these products and use them only for the symptomatic relief of acute symptoms. Arformoterol tartrate inhalation solution should not be used in conjunction with other inhaled medications containing long-acting beta 2 -agonists. Patients should be warned not to stop or change the dose of other concomitant COPD therapy without medical advice, even if symptoms improve after initiating treatment with arformoterol tartrate inhalation solution. Common Adverse Reactions with Beta 2 -agonists Patients should be informed that treatment with beta 2 -agonists may lead to adverse reactions that include palpitations, chest pain, rapid heart rate, increased or decreased blood pressure, headache, tremor, nervousness, dry mouth, muscle cramps, nausea, dizziness, fatigue, malaise, low blood potassium, high blood sugar, high blood acid, or trouble sleeping [see Adverse Reactions (6.1)] . Instructions for Administration It is important that patients understand how to use arformoterol tartrate inhalation solution with a nebulizer appropriately and how it should be used in relation to other medications to treat COPD they are taking [see the accompanying Patient Information]. Patients should be instructed not to mix other medications with arformoterol tartrate inhalation solution and not to inject or swallow arformoterol tartrate inhalation solution. Patients should throw the plastic dispensing vials away immediately after use. Due to their small size, the vials pose a danger of choking to young children. Women should be advised to contact their physician if they become pregnant or if they are nursing. FDA-Approved Patient Information See the accompanying Patient Information . All trademarks are the property of their respective owners. Manufactured by: Sun Pharmaceutical Industries Limited Baska Ujeti Road, Ujeti Halol-389350, Gujarat, India. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512
Label text from the FDA structured product label by Sun Pharmaceutical Industries, Inc. (revised Apr 14, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Arformoterol Tartrate in 11 products
Arformoterol Tartrate NDC products (11)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 62332-633 | Arformoterol Tartrate 15 ug/2mL Solution | Alembic Pharmaceuticals Inc. | ANDA |
| 60687-770 | Arformoterol Tartrate 15 ug/2mL Solution | American Health Packaging | ANDA |
| 69097-168 | Arformoterol Tartrate 15 ug/2mL Solution | Cipla USA Inc. | ANDA |
| 43598-777 | Arformoterol Tartrate 15 ug/2mL Solution | Dr. Reddy's Laboratories, Inc. | ANDA |
| 72266-259 | Arformoterol Tartrate 15 ug/2mL Solution | Fosun Pharma USA Inc. | ANDA |
| 50742-395 | Arformoterol Tartrate 15 ug/2mL Solution | Ingenus Pharmaceuticals, LLC | ANDA |
| 70756-612 | Arformoterol Tartrate 15 ug/2mL Solution | Lifestar Pharma LLC | ANDA |
| 70748-175 | Arformoterol Tartrate 15 ug/2mL Solution | Lupin Pharmaceuticals, Inc. | ANDA |
| 42571-464 | Arformoterol Tartrate 15 ug/2mL Solution | Micro Labs Limited | ANDA |
| 72603-208 | Arformoterol Tartrate 15 ug/2mL Solution | NorthStar RxLLC | ANDA |
| 62756-277 | Arformoterol Tartrate 15 ug/2mL Solution | Sun Pharmaceutical Industries, Inc. | ANDA |
Arformoterol Tartrate recalls
- D-1550-2022 Oct 12, 2022 · Class II · Terminated
Lack of Assurance of Sterility: environmental monitoring failure.
Frequently asked questions
What is Arformoterol Tartrate used for?
Arformoterol tartrate inhalation solution is a long-acting beta 2 -adrenergic agonist (beta 2 -agonist) indicated for: Long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. (1.1) Important limitations of use: Arformoterol tartrate…
What are the side effects of Arformoterol Tartrate?
Long-acting beta 2 -adrenergic agonists, such as arformoterol tartrate, as monotherapy (without inhaled corticosteroids) for asthma increase the risk of asthma-related events. Arformoterol tartrate inhalation solution is not indicated for the treatment of asthma [see Warnings and Precautions (5.1)]. Most common adverse reactions (≥2% incidence and more common than placebo) are pain, chest pain,… See the full label for the complete list.
Who makes Arformoterol Tartrate?
Arformoterol Tartrate is listed by 11 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., American Health Packaging, Cipla USA Inc., Dr. Reddy's Laboratories, Inc..
Has Arformoterol Tartrate been recalled?
The FDA enforcement database lists 1 recall for Arformoterol Tartrate, most recently D-1550-2022 (class ii): Lack of Assurance of Sterility: environmental monitoring failure.