Arformoterol Tartrate Inhalation Solution

FDA Drug Information • Also known as: Arformoterol Tartrate Inhalation Solution

Brand Names: Arformoterol Tartrate Inhalation Solution
Route: RESPIRATORY (INHALATION)
Dosage Form: SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11. 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-dihydroxybutanedioate (1:1 salt), and its established structural formula is as follows: The molecular weight of arformoterol tartrate is 494.5 g/mol, and its empirical formula is C 19 H 24 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™ 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...

What Is Arformoterol Tartrate Inhalation Solution Used For?

1. INDICATIONS AND USAGE 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 inidcated 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

2. 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)

Side Effects (Adverse Reactions)

6. ADVERSE REACTIONS 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 Ritedose Pharmaceuticals, LLC at 1-855-806-3300 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. Table 1: Number of Patients Experiencing Adverse Events from Two 12-Week, Double-Blind, Placebo-Controlled Clinical Trials Arformoterol Tartrate Inhalation Solution 15 mcg twice daily Placebo n (%) n (%) Total Patients 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) 7 (2) Flu Syndrome 10 (3) 4 (1) Peripheral Edema 8 (3) 7 (2) Lung Disorder* 7 (2) 2 (1) *reported termscoded 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...

Drug Interactions

7. 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 2-3 bpm and 6-8 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 co-administration 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...

Contraindications

4. 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)

Pregnancy and Breastfeeding

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 2-4% and 15-20%, 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...

Overdosage

10. 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.

How Supplied

16. HOW SUPPLIED/STORAGE AND HANDLING 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 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 76204-026-01: carton of 30 individually pouched unit-dose vials. NDC 76204-026-02: carton of 60 individually pouched unit-dose vials. NDC 76204-026-55: carton of 60 unit-dose vials (12×5 unit-dose vial pouches). Storage and Handling Store Arformoterol Tartrate Inhalation Solution in the protective foil pouch under refrigeration at 36°-46°F (2°-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°-77°F (20°-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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.