Arformoterol Tartrate Inhalation Solution (Brovana)
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Arformoterol Tartrate Inhalation Solution (Brovana)

BROVANA®
(arformoterol tartrate)

WARNING

ASTHMA RELATED DEATH

Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including arformoterol, the active ingredient in BROVANA Inhalation Solution [see WARNINGS AND PRECAUTIONS]. The safety and efficacy of BROVANA Inhalation Solution in patients with asthma have not been established. All LABA, including BROVANA Inhalation Solution, are contraindicated in patients with asthma without use of a long-term asthma control medication [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

BROVANA (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 beta2-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)-2,3dihydroxybutanedioate (1:1 salt), and its established structural formula is as follows:

BROVANA® (arformoterol tartrate) Structural Formula Illustration

The molecular weight of arformoterol tartrate is 494.5 g/mol, and its empirical formula is C19H24N2O4•C4H6O6 (1:1 salt). It is a white to off-white solid that is slightly soluble in water.

Arformoterol tartrate is the United States Adopted Name (USAN) for (R,R)formoterol L-tartrate.

BROVANA (arformoterol tartrate) Inhalation Solution is supplied as 2 mL of arformoterol tartrate solution packaged in 2.1 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.

BROVANA 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. BROVANA 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 Medication Guide).

What are the possible side effects of arformoterol inhalation (Brovana)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • bronchospasm (wheezing, chest tightness, trouble breathing);
  • chest pain, fast or pounding heart beats, restless feeling, tremor;
  • feeling short of breath, even with mild exertion;
  • swelling, rapid weight gain;
  • white patches or sores inside your mouth or on your lips; or
  • dry mouth, increased...

Read All Potential Side Effects and See Pictures of Brovana »

What are the precautions when taking arformoterol tartrate inhalation solution (Brovana)?

Before using arformoterol, tell your doctor or pharmacist if you are allergic to it; or to formoterol; or to sympathomimetic drugs (e.g., phenylephrine, pseudoephedrine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems (e.g., irregular heartbeat, angina), high blood pressure, overactive thyroid (hyperthyroidism), seizures, diabetes, liver problems, certain metabolic problem (ketoacidosis).

Arformoterol may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely...

Read All Potential Precautions of Brovana »

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Maintenance Treatment of COPD

BROVANA (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. BROVANA Inhalation Solution is for use by nebulization only.

Important Limitations of Use

BROVANA Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease [see WARNINGS AND PRECAUTIONS]

BROVANA Inhalation Solution is not indicated to treat asthma. The safety and effectiveness of BROVANA Inhalation Solution in asthma have not been established.

DOSAGE AND ADMINISTRATION

The recommended dose of BROVANA (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.

BROVANA Inhalation Solution should be administered by the orally inhaled route via a standard jet nebulizer connected to an air compressor (see the accompanying Medication Guide). BROVANA Inhalation Solution should not be swallowed. BROVANA 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 BROVANA Inhalation Solution is prolonged in patients with hepatic impairment, they should be monitored closely.

The drug compatibility (physical and chemical), efficacy, and safety of BROVANA Inhalation Solution when mixed with other drugs in a nebulizer have not been established.

The safety and efficacy of BROVANA Inhalation Solution have been established in clinical trials when administered using the PARI LC® Plus nebulizer (with a facemask or mouth piece) and the PARI DURA NEB™ 3000 compressor. The safety and efficacy of BROVANA Inhalation Solution delivered from non-compressor based nebulizer systems have not been established.

HOW SUPPLIED

Dosage Forms And Strengths

BROVANA (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.

BROVANA (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. BROVANA Inhalation Solution is available in a shelf-carton containing 30 or 60 unit-dose vials.

NDC 63402-911-30: carton of 30 individually pouched unit-dose vials.

NDC 63402-911-64: carton of 60 unit-dose vials (15×4 unit-dose vial pouches).

Storage and Handling

Store BROVANA 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 BROVANA 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.

Manufactured for: Sunovion Pharmaceuticals Inc. Marlborough, MA 01752 USA.

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Long acting beta2-adrenergic agonists increase the risk of asthma-related death [See BOXED WARNING and WARNINGS AND PRECAUTIONS].

Beta2-Agonist Adverse Reaction Profile

Adverse reactions to BROVANA Inhalation Solution are expected to be similar in nature to other beta2-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.

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.

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 BROVANA 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.

Adults with COPD

Among 1,456 COPD patients in two 12-week, placebo-controlled trials, 288 were treated with BROVANA 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 BROVANA Inhalation Solution 15 mcg twice daily group and where the rate in the BROVANA 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

Total Patients BROVANA Placebo
15 mcg twice daily  
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 BROVANA 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 BROVANA Inhalation Solution 15 mcg twice daily and 13.3% in the placebo group. There were no frequently occurring specific cardiovascular adverse events for BROVANA Inhalation Solution (frequency ≥ 1% and greater than placebo). The rate of COPD exacerbations was also comparable between the BROVANA Inhalation Solution 15 mcg twice daily and placebo groups, 12.2% and 15.1%, respectively

Read the Brovana (arformoterol tartrate inhalation solution) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

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].

Xanthine Derivatives, Steroids, or Diuretics

Concomitant treatment with methylxanthine (aminophylline, theophylline), steroids, or diuretics may potentiate any hypokalemic effect of adrenergic agonists including BROVANA Inhalation Solution [see WARNINGS AND PRECAUTIONS].

The concurrent use of intravenously or orally administered methylxanthines (e.g., aminophylline, theophylline) by patients receiving BROVANA Inhalation Solution has not been completely evaluated. In two combined 12-week placebo controlled trials that included BROVANA Inhalation Solution doses of 15 mcg twice daily, 25 mcg twice daily, and 50 mcg once daily, 54 of 873 BROVANA Inhalation Solution treated subjects received concomitant theophylline at study entry. In a 12 month controlled trial that included a 50 mcg once daily BROVANA Inhalation Solution dose, 30 of the 528 BROVANA 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.

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 BROVANA Inhalation Solution with non-potassium sparing diuretics.

MAO Inhibitors, Tricyclic Antidepressants, QTc Prolonging Drugs

BROVANA 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 QTc interval have an increased risk of ventricular arrhythmias.

Beta-Blockers

Beta-adrenergic receptor antagonists (beta-blockers) and BROVANA 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.

Drug Abuse And Dependence

There were no reported cases of abuse or evidence of drug dependence with the use of BROVANA Inhalation Solution in the clinical trials.

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

  • ASTHMA RELATED DEATH

Long-acting beta2-adrcncrgic agonists increase the risk of asthma-related death. The safety and efficacy of BROVANA (arformoterol tartrate inhalation solution) in patients with asthma have not been established. All LABA, including BROVANA (arformoterol tartrate inhalation solution) , are contraindicated in patients with asthma without use of a long-term asthma control medication (see CONTRAINDICATIONS).

    • A 28-week, placebo-controlled US study comparing the safety of 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 long-acting beta2-adrenergic agonists, including BROVANA (arformoterol tartrate inhalation solution) . No study adequate to determine whether the rate of asthma related death is increased in patients treated with BROVANA (arformoterol tartrate inhalation solution) has been conducted.

Clinical studies with racemic formoterol (Foradil® Aerolizer™) 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.

  • The studies described above enrolled patients with asthma. Data are not available to determine whether the rate of death in patients with COPD is increased by long-acting beta2-adrenergic agonists.
  • BROVANA (arformoterol tartrate inhalation solution) is indicated for the long term, twice daily (morning and evening) maintenance treatment for bronchoconstriction in chronic obstructive pulmonary disease (COPD), and is not indicated for the treatment of acute episodes of bronchospasm, i.e., rescue therapy.
  • BROVANA (arformoterol tartrate inhalation solution) should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. The use of BROVANA (arformoterol tartrate inhalation solution) in this setting is inappropriate.
  • BROVANA (arformoterol tartrate inhalation solution) should not be used in children as the safety and efficacy of BROVANA (arformoterol tartrate inhalation solution) have not been established in pediatric patients.
  • BROVANA (arformoterol tartrate inhalation solution) should not be used in conjunction with other inhaled, long-acting beta2-agonists. BROVANA (arformoterol tartrate inhalation solution) should not be used with other medications containing long-acting beta2-agonists.
  • When beginning treatment with BROVANA (arformoterol tartrate inhalation solution) , patients who have been taking inhaled, short-acting beta2-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.
  • See PRECAUTIONS, Information for Patients and the accompanying Medication Guide.

Paradoxical Bronchospasm

As with other inhaled beta2-agonists, BROVANA (arformoterol tartrate inhalation solution) can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, BROVANA (arformoterol tartrate inhalation solution) should be discontinued immediately and alternative therapy instituted.

Deterioration of Disease

COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If BROVANA (arformoterol tartrate inhalation solution) no longer controls the symptoms of bronchoconstriction, or the patient's inhaled, short-acting beta2-agonist becomes less effective or the patient needs more inhalation of short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting, a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dosage of BROVANA (arformoterol tartrate inhalation solution) beyond the recommended 15 mcg twice daily dose is not appropriate in this situation.

Cardiovascular Effects

BROVANA (arformoterol tartrate inhalation solution) , like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of BROVANA (arformoterol tartrate inhalation solution) at the recommended dose, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. BROVANA (arformoterol tartrate inhalation solution) , as with other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension (see PRECAUTIONS, General).

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions may occur after administration of BROVANA (arformoterol tartrate inhalation solution) as demonstrated by cases of anaphylactic reaction, urticaria, angioedema, rash and bronchospasm.

Do Not Exceed Recommended Dose

Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. As with other inhaled beta2-adrenergic drugs, BROVANA (arformoterol tartrate inhalation solution) should not be used more often, at higher doses than recommended, or with other long-acting beta-agonists.

PRECAUTIONS

General

BROVANA (arformoterol tartrate) Inhalation Solution should not be used to treat acute symptoms of COPD. BROVANA (arformoterol tartrate inhalation solution) has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. When prescribing BROVANA (arformoterol tartrate inhalation solution) , the physician should also provide the patient with an inhaled, short-acting beta2-agonist for treatment of COPD symptoms that occur acutely, despite regular twice-daily (morning and evening) use of BROVANA (arformoterol tartrate inhalation solution) . Patients should also be cautioned that increasing inhaled beta2-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated (see Information for Patients and the accompanying Medication Guide).

BROVANA (arformoterol tartrate inhalation solution) , like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive disorders or thyrotoxicosis; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and/or diastolic blood pressure, pulse rate and electrocardiograms have been seen infrequently in individual patients in controlled clinical studies with arformoterol tartrate. Doses of the related beta2-agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Beta-agonist medications may produce significant hypokalemia in some patients, possibly though intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation.

Clinically significant changes in blood glucose and/or serum potassium were infrequent during clinical studies with long-term administration of BROVANA (arformoterol tartrate inhalation solution) at the recommended dose.

Information for Patients

Patients should be instructed to read the accompanying Medication Guide with each new prescription and refill. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be given the following information:

  1. Patients should be informed that long-acting beta2-adrenergic agonists, such as BROVANA (arformoterol tartrate inhalation solution) , increase the risk of asthma-related death. All LAB A, including BROVANA (arformoterol tartrate inhalation solution) , should not be used in patients with asthma without use of a long-term asthma control medication (see CONTRAINDICATIONS).
  2. BROVANA (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, beta2-agonist (the health-care 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, if BROVANA (arformoterol tartrate inhalation solution) treatment becomes less effective, or if they need more inhalations of a short-acting beta2-agonist than usual. Patients should not inhale more than one dose at any one time. The daily dosage of BROVANA (arformoterol tartrate inhalation solution) should not exceed one ready-to-use vial (15 mcg) by inhalation twice daily (30 mcg total daily dose).
  3. Patients should be informed that treatment with beta2-agonists may lead to adverse events which include palpitations, chest pain, rapid heart rate, tremor, or nervousness.
  4. Patients should be instructed to use BROVANA (arformoterol tartrate inhalation solution) by nebulizer only and not to inject or swallow this inhalation solution.
  5. Patients should protect BROVANA (arformoterol tartrate inhalation solution) ready-to-use vials from light and excessive heat. The protective foil pouches should be stored under refrigeration between 2°C and 8°C (36°- 6°F). They should not be used after the expiration date stamped on the container. After opening the pouch, unused ready-to-use vials should be returned to, and stored in, the pouch. An opened ready-to-use vial should be used right away. Discard any ready-to-use vial if the solution is not colorless.
  6. The drug compatibility (physical and chemical), efficacy and safety of BROVANA (arformoterol tartrate inhalation solution) when mixed with other drugs in a nebulizer have not been established.
  7. Women should be advised to contact their physician if they become pregnant or if they are nursing.
  8. It is important that patients understand how to use BROVANA (arformoterol tartrate inhalation solution) appropriately and how it should be used in relation to other medications to treat COPD they are taking (see the accompanying Medication Guide and the Instructions for Using BROVANA (arformoterol tartrate inhalation solution) ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies were conducted in mice using oral administration and rats using inhalation administration to evaluate the carcinogenic potential of arformoterol.

In a 24-month carcinogenicity study in CD-1 mice, arformoterol caused a dose-related increase in the incidence of uterine and cervical endometrial stromal polyps and stromal cell sarcoma in female mice at oral doses of 1 mg/kg and above (AUC exposure approximately 70 times adult exposure at the maximum recommended daily inhalation dose).

In a 24-month carcinogenicity study in Sprague-Dawley rats, arformoterol caused a statistically significant increase in the incidence of thyroid gland c-cell adenoma and carcinoma in female rats at an inhalation dose of 200 mcg/kg (AUC exposure approximately 130 times adult exposure at the maximum recommended daily inhalation dose). There were no tumor findings with an inhalation dose of 40 mcg/kg (AUC exposure approximately 55 times adult exposure at the maximum recommended daily inhalation dose).

Arformoterol was not mutagenic or clastogenic in the following tests: mutagenicity tests in bacteria, chromosome aberration analyses in mammalian cells, and micronucleus test in mice.

Arformoterol had no effects on fertility and reproductive performance in rats at oral doses up to 10 mg/kg (approximately 2700 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis).

Pregnancy: Teratogenic Effects

Pregnancy Category C

Arformoterol has been shown to be teratogenic in rats based upon findings of omphalocele (umbilical hernia), a malformation, at oral doses of 1 mg/kg and above (AUC exposure approximately 370 times adult exposure at the maximum recommended daily inhalation dose). Increased pup loss at birth and during lactation and decreased pup weights were observed in rats at oral doses of 5 mg/kg and above (AUC exposure approximately 1100 times adult exposure at the maximum recommended daily inhalation dose). Delays in development were evident with an oral dose of 10 mg/kg (AUC exposure approximately 2400 times adult exposure at the maximum recommended daily inhalation dose).

Arformoterol has been shown to be teratogenic in rabbits based upon findings of malpositioned right kidney, a malformation, at oral doses of 20 mg/kg and above (AUC exposure approximately 8400 times adult exposure at the maximum recommended daily inhalation dose). Malformations including brachydactyly, bulbous aorta, and liver cysts were observed at doses of 40 mg/kg and above (approximately 22,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). Malformation including adactyly, lobular dysgenesis of the lung, and interventricular septal defect were observed at 80 mg/kg (approximately 43,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). Embryolethality was observed at 80 mg/kg/day (approximately 43,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). Decreased pup body weights were observed at doses of 40 mg/kg/day and above (approximately 22,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). There were no teratogenic findings in rabbits with oral dose of 10 mg/kg and lower (AUC exposure approximately 4900 times adult exposure at the maximum recommended daily inhalation dose).

There are no adequate and well-controlled studies in pregnant women. BROVANA (arformoterol tartrate inhalation solution) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in Labor and Delivery

There are no human studies that have investigated the effects of BROVANA (arformoterol tartrate inhalation solution) on preterm labor or labor at term.

Because beta-agonists may potentially interfere with uterine contractility, BROVANA (arformoterol tartrate inhalation solution) should be used during labor and delivery only if the potential benefit justifies the potential risk.

Nursing Mothers

In reproductive studies in rats, arformoterol was excreted in the milk. It is not known whether arformoterol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BROVANA (arformoterol tartrate inhalation solution) is administered to a nursing woman.

Pediatric

BROVANA (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 effectiveness of BROVANA (arformoterol tartrate inhalation solution) in pediatric patients have not been established.

Geriatric

Of the 873 patients who received BROVANA (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 BROVANA (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 BROVANA (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.

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

The expected signs and symptoms associated with overdosage of BROVANA (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 BROVANA Inhalation Solution.

Treatment of overdosage consists of discontinuation of BROVANA 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 BROVANA Inhalation Solution. Cardiac monitoring is recommended in cases of overdosage.

Clinical signs in dogs included flushing of the body surface and facial area, reddening of the ears and gums, tremor, and increased heart rate. A death was reported in dogs after a single oral dose of 5 mg/kg (approximately 4500 times the maximum structural formula recommended daily inhalation dose in adults on a mg/m² basis). Death occurred for a rat that received arformoterol at a single inhalation dose of 1600 mcg/kg (approximately 430 times the maximum recommended daily inhalation dose in adults on a mg/m² basis).

CONTRAINDICATIONS

BROVANA Inhalation Solution is contraindicated in patients with a history of hypersensitivity to arformoterol, racemic formoterol or to any other components of this product.

All LABA, including BROVANA Inhalation Solution, are contraindicated in patients with asthma without use of a long-term asthma control medication [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Arformoterol, the (R,R)-enantiomer of formoterol, is a selective long-acting beta2 -adrenergic receptor agonist (beta2-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 beta2-agonist than the (R,R)-enantiomer. While it is recognized that beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, data indicate that there are also beta2-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 beta2-agonists may have cardiac effects.

The pharmacologic effects of beta2-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.

Pharmacodynamics

Systemic Safety and Pharmacokinetic/Pharmacodynamic Relationships

The predominant adverse effects of inhaled beta2-agonists occur as a result of excessive activation of systemic beta-adrenergic receptors. The most common adverse effects may include skeletal muscle tremor and cramps, insomnia, tachycardia, decreases in plasma potassium, and increases in plasma glucose.

Effects on Serum Potassium and Serum Glucose Levels

Changes in serum potassium and serum glucose were evaluated in a dose ranging study of twice daily (5 mcg, 15 mcg, or 25 mcg; 215 patients with COPD) and once daily (15 mcg, 25 mcg, or 50 mcg; 191 patients with COPD) BROVANA Inhalation Solution in COPD patients. At 2 and 6 hours post dose at week 0 (after the first dose), mean changes in serum potassium ranging from 0 to –0.3 mEq/L were observed in the BROVANA Inhalation Solution groups with similar changes observed after 2 weeks of treatment. Changes in mean serum glucose levels, ranging from a decrease of 1.2 mg/dL to an increase of 32.8 mg/dL were observed for BROVANA Inhalation Solution dose groups at both 2 and 6 hours post dose, both after the first dose and 14 days of daily treatment.

Electrophysiology

The effect of BROVANA Inhalation Solution on QT interval was evaluated in a dose ranging study following multiple doses of BROVANA Inhalation Solution 5 mcg, 15 mcg, or 25 mcg twice daily or 15 mcg, 25 mcg, or 50 mcg once daily for 2 weeks in patients with COPD. ECG assessments were performed at baseline, time of peak plasma concentration and throughout the dosing interval. Different methods of correcting for heart rate were employed, including a subject-specific method and the Fridericia method.

Relative to placebo, the mean change in subject-specific QTc averaged over the dosing interval ranged from -1.8 to 2.7 msec, indicating little effect of BROVANA Inhalation Solution on cardiac repolarization after 2 weeks of treatment. The maximum mean change in subject-specific QTc for the BROVANA Inhalation Solution 15 mcg twice daily dose was 17.3 msec, compared with 15.4 msec in the placebo group. No apparent correlation of QTc with arformoterol plasma concentration was observed.

Electrocardiographic Monitoring in Patients with COPD

The effect of different doses of BROVANA Inhalation Solution on cardiac rhythm was assessed using 24-hour Holter monitoring in two 12-week double-blind, placebo-controlled studies of 1,456 patients with COPD (873 received BROVANA Inhalation Solution at 15 or 25 mcg twice daily or 50 mcg once daily doses; 293 received placebo; 290 received salmeterol). The 24-hour Holter monitoring occurred once at baseline, and up to 3 times during the 12-week treatment period. The rates of new-onset cardiac arrhythmias not present at baseline over the double-blind 12-week treatment period were similar (approximately 33-34%) for patients who received BROVANA Inhalation Solution 15 mcg twice daily to those who received placebo. There was a dose-related increase in new, treatment emergent arrhythmias seen in patients who received BROVANA Inhalation Solution 25 mcg twice daily and 50 mcg once daily, 37.6% and 40.1 %, respectively. The frequencies of new treatment emergent events of non-sustained (3-10 beat run) and sustained ( > 10 beat run) ventricular tachycardia were 7.4% and 1.1% in BROVANA Inhalation Solution 15 mcg twice daily and 6.9% and 1.0% in placebo. In patients who received BROVANA Inhalation Solution 25 mcg twice daily and 50 mcg once daily the frequencies of non-sustained (6.2% and 8.2%, respectively) and sustained ventricular tachycardia (1.0% and 1.0%, respectively) were similar. Five cases of ventricular tachycardia were reported as adverse events (1 in BROVANA Inhalation Solution 15 mcg twice daily and 4 in placebo), with two of these events leading to discontinuation of treatment (2 in placebo).

There were no baseline occurrences of atrial fibrillation/ flutter observed on 24-hour Holter monitoring in patients treated with BROVANA Inhalation Solution 15 mcg twice daily or placebo. New, treatment emergent atrial fibrillation/ flutter occurred in 0.4% of patients who received BROVANA Inhalation Solution 15 mcg twice daily and 0.3% of patients who received placebo. There was a dose-related increase in the frequency of atrial fibrillation/ flutter reported in the BROVANA Inhalation Solution 25 mcg twice daily and 50 mcg once daily dose groups of 0.7% and 1.4%, respectively. Two cases of atrial fibrillation/ flutter were reported as adverse events (1 in BROVANA Inhalation Solution 15 mcg twice daily and 1 in placebo).

Dose-related increases in mean maximum change in heart rate in the 12 hours after dosing were also observed following 12 weeks of dosing with BROVANA Inhalation Solution 15 mcg twice daily (8.8 bpm), 25 mcg twice daily (9.9 bpm) and 50 mcg once daily (12 bpm) versus placebo (8.5 bpm).

Tachyphylaxis/ Tolerance

Tolerance to the effects of inhaled beta-agonists can occur with regularly-scheduled, chronic use.

In two placebo-controlled clinical trials in patients with COPD involving approximately 725 patients in each, the overall efficacy of BROVANA Inhalation Solution was maintained throughout the 12-week trial duration. However, tolerance to the bronchodilator effect of BROVANA Inhalation Solution was observed after 6 weeks of dosing, as measured by a decrease in trough FEV1. FEV1 improvement at the end of the 12-hour dosing interval decreased by approximately one third (22.1% mean improvement after the first dose compared to 14.6% at week 12). Tolerance to the trough FEV1 bronchodilator effect of BROVANA Inhalation Solution was not accompanied by other clinical manifestations of tolerance in these trials.

Pharmacokinetics

The pharmacokinetics (PK) of arformoterol have been investigated in healthy subjects, elderly subjects, renally and hepatically impaired subjects, and COPD patients following the nebulization of the recommended therapeutic dose and doses up to 96 mcg.

Absorption

In COPD patients administered 15 mcg arformoterol every 12 hours for 14 days, the mean steady-state peak (R,R)-formoterol plasma concentration (Cmax) and systemic exposure (AUC0-12h) were 4.3 pg/mL and 34.5 pg*hr/mL, respectively. The median steady-state peak (R,R)-formoterol plasma concentration time (tmax) was observed approximately one half hour after drug administration.

Systemic exposure to (R,R)-formoterol increased linearly with dose in COPD patients following arformoterol doses of 5 mcg, 15 mcg, or 25 mcg twice daily for 2 weeks or 15 mcg, 25 mcg, or 50 mcg once daily for 2 weeks.

In a crossover study in patients with COPD, when arformoterol 15 mcg inhalation solution and 12 and 24 mcg formoterol fumarate inhalation powder (Foradil® Aerolizer®) was administered twice daily for 2 weeks, the accumulation index was approximately 2.5 based on the plasma (R,R)-formoterol concentrations in all three treatments. At steady state, geometric means of systemic exposure (AUC0-12h) to (R,R)-formoterol following 15 mcg of arformoterol inhalation solution and 12 mcg of formoterol fumarate inhalation powder were 39.33 pg*hr/mL and 33.93 pg*hr/mL, respectively (ratio 1.16; 90% CI 1.00, 1.35), while the geometric means of the Cmax were 4.30 pg/mL and 4.75 pg/mL, respectively (ratio 0.91; 90% CI 0.76, 1.09).

In a study in patients with asthma, treatment with arformoterol 50 mcg with pre- and post-treatment with activated charcoal resulted in a geometric mean decrease in (R,R)-formoterol AUC0-6h by 27% and Cmax by 23% as compared to treatment with arformoterol 50 mcg alone. This suggests that a substantial portion of systemic drug exposure is due to pulmonary absorption.

Distribution

The binding of arformoterol to human plasma proteins in vitro was 52-65% at concentrations of 0.25, 0.5 and 1.0 ng/mL of radiolabeled arformoterol. The concentrations of arformoterol used to assess the plasma protein binding were higher than those achieved in plasma following inhalation of multiple doses of 50 mcg arformoterol.

Metabolism

In vitro profiling studies in hepatocytes and liver microsomes have shown that arformoterol is primarily metabolized by direct conjugation (glucuronidation) and secondarily by O-demethylation. At least five human uridine diphosphoglucuronosyltransferase (UGT) isozymes catalyze arformoterol glucuronidation in vitro . Two cytochrome P450 isozymes (CYP2D6 and secondarily CYP2C19) catalyze the O-demethylation of arformoterol.

Arformoterol was almost entirely metabolized following oral administration of 35 mcg of radiolabeled arformoterol in eight healthy subjects. Direct conjugation of arformoterol with glucuronic acid was the major metabolic pathway. Most of the drug-related material in plasma and urine was in the form of glucuronide or sulfate conjugates of arformoterol. O-Desmethylation and conjugates of the O-desmethyl metabolite were relatively minor metabolites accounting for less than 17% of the dose recovered in urine and feces.

Elimination

After administration of a single oral dose of radiolabeled arformoterol to eight healthy male subjects, 63% of the total radioactive dose was recovered in urine and 11% in feces within 48 hours. A total of 89% of the total radioactive dose was recovered within 14 days, with 67% in urine and 22% in feces. Approximately 1% of the dose was recovered as unchanged arformoterol in urine over 14 days. Renal clearance was 8.9 L/hr for unchanged arformoterol in these subjects.

In COPD patients given 15 mcg inhaled arformoterol twice a day for 14 days, the mean terminal half-life of arformoterol was 26 hours.

Special Populations

Gender

A population PK analysis indicated that there was no effect of gender upon the pharmacokinetics of arformoterol.

Race

The influence of race on arformoterol pharmacokinetics was assessed using a population PK analysis and data from healthy subjects. There was no clinically significant impact of race upon the pharmacokinetic profile of arformoterol.

Geriatric

The pharmacokinetic profile of arformoterol in 24 elderly subjects (aged 65 years or older) was compared to a younger cohort of 24 subjects (18-45 years) that were matched for body weight and gender. No significant differences in systemic exposure (AUC and Cmax) were observed when the two groups were compared.

Pediatric

The pharmacokinetics of arformoterol have not been studied in pediatric subjects.

Hepatic Impairment

The pharmacokinetic profile of arformoterol was assessed in 24 subjects with mild, moderate, and severe hepatic impairment. The systemic exposure (Cmax and AUC) to arformoterol increased 1.3 to 2.4-fold in subjects with hepatic impairment compared to 16 demographically matched healthy control subjects. No clear relationship between drug exposure and the severity of hepatic impairment was observed. BROVANA Inhalation Solution should be used cautiously in patients with hepatic impairment.

Renal Impairment

The impact of renal disease upon the pharmacokinetics of arformoterol was studied in 24 subjects with mild, moderate, or severe renal impairment. Systemic exposure (AUC and Cmax) to arformoterol was similar in renally impaired patients compared with demographically matched healthy control subjects.

Drug-Drug Interaction

When paroxetine, a potent inhibitor of CYP2D6, was co-administered with BROVANA Inhalation Solution at steady-state, exposure to either drug was not altered. Dosage adjustments of BROVANA Inhalation Solution are not necessary when the drug is given concomitantly with potent CYP2D6 inhibitors.

Arformoterol did not inhibit CYP1A2, CYP2A6, CYP2C9/10, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, or CYP4A9/11 enzymes at > 1,000-fold higher concentrations than the expected peak plasma concentrations following a therapeutic dose.

Pharmacogenetics

Arformoterol is eliminated through the action of multiple drug metabolizing enzymes. Direct glucuronidation of arformoterol is mediated by several UGT enzymes and is the primary elimination route. O-Desmethylation is a secondary route catalyzed by the CYP enzymes CYP2D6 and CYP2C19. In otherwise healthy subjects with reduced CYP2D6 and/or UGT1A1 enzyme activity, there was no impact on systemic exposure to arformoterol compared to subjects with normal CYP2D6 and/or UGT1A1 enzyme activities.

Animal Toxicology and/or Pharmacology

Animal Pharmacology

In animal studies investigating its cardiovascular effects, arformoterol induced dose-dependent increases in heart rate and decreases in blood pressure consistent with its pharmacology as a beta-adrenergic agonist. In dogs, at systemic exposures higher than anticipated clinically, arformoterol also induced exaggerated pharmacologic effects of a beta-adrenergic agonist on cardiac function as measured by electrocardiogram (sinus tachycardia, atrial premature beats, ventricular escape beats, PVCs).

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown.

Reproductive Toxicology Studies

Arformoterol has been shown to be teratogenic in rats based upon findings of omphalocele (umbilical hernia), a malformation, at oral doses of 1 mg/kg and above (AUC exposure approximately 370 times adult exposure at the maximum recommended daily inhalation dose). Increased pup loss at birth and during lactation and decreased pup weights were observed in rats at oral doses of 5 mg/kg and above (AUC exposure approximately 1100 times adult exposure at the maximum recommended daily inhalation dose). Delays in development were evident with an oral dose of 10 mg/kg (AUC exposure approximately 2400 times adult exposure at the maximum recommended daily inhalation dose).

Arformoterol has been shown to be teratogenic in rabbits based on upon findings of malpositioned right kidney, a malformation, at oral doses of 20 mg/kg and above (AUC exposure approximately 8400 times adult exposure at the maximum recommended daily inhalation dose). Malformations including brachydactyly, bulbous aorta, and liver cysts were observed at doses of 40 mg/kg and above (approximately 22,000 times the maximum recommended daily inhalation dose in adults on a mg/m² basis). Malformation including adactyly, lobular dysgenesis of the lung, interventricular septal defect were observed at 80 mg/kg (approximately 43,000 times the maximum recommended daily inhalation dose in adults on a mg/m² basis). Embryolethality was observed at 80 mg/kg/day (approximately 43,000 times the maximum recommended daily inhalation dose in adults on a mg/m² basis). Decreased pup body weights were observed at doses of 40 mg/kg/day and above (approximately 22,000 times the maximum recommended daily inhalation dose in adults on a mg/m² basis). There were no teratogenic findings in rabbits with oral dose of 10 mg/kg and lower (AUC exposure approximately 4900 times adult exposure at the maximum recommended daily inhalation dose).

Clinical Studies

Adult COPD Trials

BROVANA (arformoterol tartrate) Inhalation Solution was studied in two identical, 12-week, double-blind, placebo- and active-controlled, randomized, multicenter, parallel group trials conducted in the United States (Clinical Trial A and Clinical Trial B). A total of 1,456 adult patients (age range: 34 to 89 years; mean age: 63 years; gender: 860 males and 596 females) with COPD who had a mean FEV1 of 1.3 L (42% of predicted) were enrolled in the two clinical trials. The racial/ethnic distribution in these two trials included 1383 Caucasians, 49 Blacks, 10 Asians, and 10 Hispanics, and 4 patients classified as Other. The diagnosis of COPD was based on a prior clinical diagnosis of COPD, a smoking history (greater than 15 pack-years), age (at least 35 years), spirometry results (baseline FEV1 ≤ 65% of predicted value and > 0.70 L, and a FEV1/ forced vital capacity (FVC) ratio ≤ 70%). About 80% of patients in these studies had bronchodilator reversibility, defined as a 10% or greater increase FEV1 after inhalation of 2 actuations (180 mcg racemic albuterol from a metered dose inhaler). Both trials compared BROVANA Inhalation Solution 15 mcg twice daily (288 patients), 25 mcg twice daily (292 patients), 50 mcg once daily (293 patients) with placebo (293 subjects). Both trials included salmeterol inhalation aerosol, 42 mcg twice daily as an active comparator (290 patients).

In both 12-week trials, BROVANA Inhalation Solution 15 mcg twice daily resulted in a statistically significant change of approximately 11% in mean FEV1 (as measured by percent change from study baseline FEV1 at the end of the dosing interval over the 12 weeks of treatment, the primary efficacy endpoint) compared to placebo.

Compared to BROVANA Inhalation Solution 15 mcg twice daily, BROVANA Inhalation Solution 25 mcg twice daily and 50 mcg once daily did not provide sufficient additional benefit on a variety of endpoints, including FEV1, to support the use of higher doses. Plots of the mean change in FEV1 values obtained over the 12 hours after dosing for the BROVANA Inhalation Solution 15 mcg twice daily dose group and for the placebo group are provided in Figures 1 and 2 for Clinical Trial A, below. The plots include mean FEV1 change observed after the first dose and after 12 weeks of treatment. The results from Clinical Trial B were similar.

Figure 1 : Mean Change in FEV1 Over Time for Clinical Trial A at Week 0 (Day 1)

Mean Change in FEV1 Over Time for Clinical Trial A at Week 0 (Day 1) - Illustration

Figure 2 : Mean Change in FEV1 Over Time for Clinical Trial A at Week 12

Mean Change in FEV1 Over Time for Clinical Trial A at Week 12 - Illustration

BROVANA Inhalation Solution 15 mcg twice daily significantly improved bronchodilation compared to placebo over the 12 hours after dosing (FEV1 AUC0-12h). This improvement was maintained over the 12 week study period.

Following the first dose of BROVANA Inhalation Solution 15 mcg, the median time to onset of bronchodilation, defined by an FEV1 increase of 15%, occurred at 6.7 min. When defined as an increase in FEV1 of 12% and 200 mL, the time to onset of bronchodilation was 20 min after dosing. Peak bronchodilator effect was generally seen within 1-3 hours of dosing.

In both clinical trials, compared to placebo, patients treated with BROVANA Inhalation Solution demonstrated improvements in peak expiratory flow rates, supplemental ipratropium and rescue albuterol use.

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Patients should be instructed to read the accompanying Medication Guide with each new prescription and refill. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be given the following information:

Asthma-Related Deaths, Acute Exacerbations or Deteriorations

Patients should be informed that long-acting beta2-adrenergic agonists, such as BROVANA Inhalation Solution, increase risk of asthma-related death in patients with asthma.

BROVANA 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, beta2-agonist (the health-care 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 BROVANA Inhalation Solution, if BROVANA Inhalation Solution treatment becomes less effective, or if they need more inhalations of a short-acting beta2-agonist than usual.

Appropriate Dosing

Patients should not stop using BROVANA 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 BROVANA 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 beta2-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.

BROVANA Inhalation Solution should not be used in conjunction with other inhaled medications containing long-acting beta2-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 BROVANA Inhalation Solution.

Common Adverse Reactions with Beta2-agonists

Patients should be informed that treatment with beta2-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].

Instructions for Administration

It is important that patients understand how to use BROVANA 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 Medication Guide]. Patients should be instructed not to mix other medications with BROVANA Inhalation Solution and not to inject or swallow BROVANA 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.

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Patients should be instructed to read the accompanying Medication Guide with each new prescription and refill. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be given the following information:

Asthma-Related Deaths, Acute Exacerbations or Deteriorations

Patients should be informed that long-acting beta2-adrenergic agonists, such as BROVANA Inhalation Solution, increase risk of asthma-related death in patients with asthma.

BROVANA 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, beta2-agonist (the health-care 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 BROVANA Inhalation Solution, if BROVANA Inhalation Solution treatment becomes less effective, or if they need more inhalations of a short-acting beta2-agonist than usual.

Appropriate Dosing

Patients should not stop using BROVANA 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 BROVANA 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 beta2-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.

BROVANA Inhalation Solution should not be used in conjunction with other inhaled medications containing long-acting beta2-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 BROVANA Inhalation Solution.

Common Adverse Reactions with Beta2-agonists

Patients should be informed that treatment with beta2-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].

Instructions for Administration

It is important that patients understand how to use BROVANA 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 Medication Guide]. Patients should be instructed not to mix other medications with BROVANA Inhalation Solution and not to inject or swallow BROVANA 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.

Last reviewed on RxList: 8/26/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Brovana Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

ARFORMOTEROL SOLUTION - INHALATION

(AR-for-MOE-ter-ol)

COMMON BRAND NAME(S): Brovana

WARNING: Rarely, in patients treated for asthma, serious (sometimes fatal) asthma-related breathing problems have occurred with the use of long-acting inhaled beta agonists (such as salmeterol). Because arformoterol is similar to salmeterol, it may also cause these problems. Arformoterol is not approved to treat asthma. Consult your doctor or pharmacist for more details.

USES: Arformoterol is used as a long-term (maintenance) treatment to prevent or decrease breathing problems caused by ongoing lung diseases (chronic obstructive pulmonary disease-COPD, including chronic bronchitis and emphysema). It helps to reduce wheezing, coughing, and shortness of breath. Arformoterol works by opening air passages in the lungs to make breathing easier. It belongs to the class of drugs known as long-acting beta-agonist bronchodilators.

This medication does not work immediately and should not be used for sudden attacks of breathing trouble. Your doctor must prescribe a quick-relief medicine/inhaler (e.g., albuterol, also called salbutamol in other countries) for sudden shortness of breath while you are using arformoterol. You should always have a quick-relief inhaler with you.

Arformoterol is usually used in combination with other medications such as corticosteroids (inhaled or taken by mouth). However, it should not be used with other long-acting inhaled beta agonists (e.g., formoterol, salmeterol) since this may increase your risk for side effects.

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using this medication and each time you get a refill. This medication is used with a special machine called a nebulizer that changes the solution to a fine mist that you inhale. Learn all instructions for the use of this medication and the nebulizer equipment. Do not use the solution if it is discolored. Opened vials of solution should be used right away. If you have any questions, consult your doctor or pharmacist.

This medication does not require any mixing before use. Using a mouthpiece or face mask with the nebulizer, inhale the prescribed dose of medication into your lungs, usually twice daily (morning and evening) or as directed by your doctor. Each treatment usually takes about 5 to 10 minutes. Give this medication only through a nebulizer. Do not swallow the solution. Ask your doctor or pharmacist before mixing with any other medications given by nebulizer.

Use this medication regularly to receive the most benefit from it. To help you remember, use it at the same times each day. To prevent infections, clean the nebulizer and mouthpiece/face mask according to the manufacturer's directions.

Do not use more of this medication or use it more often than prescribed since this may cause serious side effects. Do not use more than 30 micrograms of arformoterol a day.

If you have been using a quick-relief inhaler (e.g., albuterol, salbutamol) on a regular daily schedule (such as 4 times daily), your doctor will direct you to stop this schedule and only use the quick-relief inhaler as needed for sudden shortness of breath. Consult your doctor for details.

Seek immediate medical attention if your breathing suddenly worsens, if this medication or your quick-relief inhaler stop working well, or if you need to use the quick-relief inhaler more often than usual (4 or more puffs daily or more than 1 inhaler every 8 weeks). Do not increase your dose of arformoterol.

Disclaimer

Brovana Consumer (continued)

SIDE EFFECTS: Shakiness (tremor), nausea, headache, nervousness, dizziness, dry mouth, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fast/pounding/irregular/slow heartbeat, muscle weakness/cramps, increased thirst/urination.

Seek immediate medical attention if any of these rare but very serious side effects occur: chest pain, severe dizziness, fainting.

Rarely, this medication has caused severe (possibly fatal), sudden worsening of breathing problems (paradoxical bronchospasm). If you have trouble breathing or experience sudden wheezing, use your quick-relief inhaler and seek immediate medical attention.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Brovana (arformoterol tartrate inhalation solution) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using arformoterol, tell your doctor or pharmacist if you are allergic to it; or to formoterol; or to sympathomimetic drugs (e.g., phenylephrine, pseudoephedrine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems (e.g., irregular heartbeat, angina), high blood pressure, overactive thyroid (hyperthyroidism), seizures, diabetes, liver problems, certain metabolic problem (ketoacidosis).

Arformoterol may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that require immediate medical attention. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm (see also Drug Interactions section). Before using arformoterol, tell your doctor or pharmacist if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using arformoterol safely.

Before having surgery, tell your doctor or dentist that you are using this medication.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this drug passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Brovana Consumer (continued)

DRUG INTERACTIONS: See also Uses section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: beta blockers (e.g., propranolol, labetalol, timolol).

Many drugs besides arformoterol may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using arformoterol, report all medications you are currently using to your doctor or pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: chest pain, fast/irregular heartbeat, severe dizziness, fainting.

NOTES: Do not share this medication with others.

Avoid smoking and other factors that make breathing worse.

Laboratory and/or medical tests (e.g., blood pressure, heart rate, lung function) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Protect this medication from light and heat. Store in the sealed protective pouch until ready to use. Refrigerate this medication between 36-46 degrees F (2-8 degrees C).

Unopened pouches of medication may also be stored at room temperature between 68-77 degrees F (20-25 degrees C) for up to 6 weeks. If stored at room temperature, discard the medication if it is not used within 6 weeks or after its expiration date, whichever is sooner.

After opening the pouch, store unused vials in the pouch. An opened vial should be used immediately. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised January 2011. Copyright(c) 2011 First Databank, Inc.

Brovana Patient Information Including Side Effects

Brand Names: Brovana

Generic Name: arformoterol inhalation (Pronunciation: ar for MOE ter ole)

What is arformoterol inhalation (Brovana)?

Arformoterol is a bronchodilator. It works by relaxing muscles in the airways to improve breathing.

Arformoterol inhalation is used to prevent bronchoconstriction in people with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Arformoterol will not treat a bronchospasm attack that has already begun.

Arformoterol may also be used for purposes not listed in this medication guide.

What are the possible side effects of arformoterol inhalation (Brovana)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • bronchospasm (wheezing, chest tightness, trouble breathing);
  • chest pain, fast or pounding heart beats, restless feeling, tremor;
  • feeling short of breath, even with mild exertion;
  • swelling, rapid weight gain;
  • white patches or sores inside your mouth or on your lips; or
  • dry mouth, increased thirst, drowsiness, restless feeling, confusion, nausea, vomiting, increased urination, muscle pain or weakness, fast heart rate, feeling light-headed, or fainting.

Less serious side effects may include:

  • weakness; headache, sleep problems (insomnia);
  • nausea, vomiting, diarrhea;
  • leg cramps;
  • fever;
  • stuffy nose; or
  • hoarseness or deepened voice.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Brovana (arformoterol tartrate inhalation solution) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about arformoterol inhalation (Brovana)?

Call your doctor right away if you feel that this medicine is not working as well as usual, or if you think you need to use more than usual. An increased need for medication could be an early sign that your condition is getting worse.

Salmeterol, a medicine similar to arformoterol, has been shown to increase the risk of asthma-related death. It is not known whether arformoterol could cause this same effect in people with chronic obstructive pulmonary disease. Use only the prescribed dose of this medication, and do not use it for longer than your doctor recommends. Follow all patient instructions for safe use. Talk with your doctor about your individual risks and benefits of using arformoterol inhalation.

Side Effects Centers

Brovana Patient Information including How Should I Take

What should I discuss with my healthcare provider before using arformoterol inhalation (Brovana)?

You should not use this medication if you are allergic to arformoterol.

Salmeterol, a medicine similar to arformoterol, has been shown to increase the risk of asthma-related death. It is not known whether arformoterol could cause this same effect in people with chronic obstructive pulmonary disease. Use only the prescribed dose of this medication, and do not use it for longer than your doctor recommends. Follow all patient instructions for safe use. Talk with your doctor about your individual risks and benefits of using arformoterol inhalation.

To make sure you can safely use arformoterol, tell your doctor if you have any of these other conditions:

  • heart disease, a heart rhythm disorder, or high blood pressure;
  • epilepsy or other seizure disorder;
  • diabetes;
  • glaucoma;
  • a thyroid disorder;
  • liver disease; or
  • a personal or family history of "Long QT syndrome."

FDA pregnancy category C. It is not known whether arformoterol will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether arformoterol passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give this medication to anyone under 18 years old without your doctor's advice.

How should I use arformoterol inhalation (Brovana)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

If you were switched from a short-acting bronchodilator to arformoterol inhalation, stop using the other bronchodilator and use it only for a sudden bronchospasm attack. Short-acting bronchodilators include albuterol (Proventil, Ventolin, Combivent), bitolterol (Tornalate), levalbuterol (Xopenex), metaproterenol (Alupent, Metaprel), or pirbuterol (Maxair).

Arformoterol solution for inhalation is for use only with a standard jet nebulizer machine connected to an air compressor. Do not mix arformoterol with other medicines in the nebulizer. Do not take this medicine by mouth or swallow it.

To use the solution with a nebulizer:

  • Open the foil pouch and squeeze all of the medicine out into the chamber of the nebulizer. Attach the mouthpiece or face mask to the drug chamber. Then, attach the drug chamber to the compressor.
  • Sit upright in a comfortable position. Place the mouthpiece into your mouth or put the face mask on, covering your nose and mouth. Turn on the compressor.
  • Breathe in slowly and evenly until you have inhaled all of the medicine (usually 5 to 10 minutes). The treatment is complete when no more mist is formed by the nebulizer and the drug chamber is empty.
  • Clean the nebulizer after each use. Follow the cleaning directions that came with your nebulizer.

Call your doctor right away if you feel that this medicine is not working as well as usual, or if you think you need to use more than usual. An increased need for medication could be an early sign that your condition is getting worse.

COPD is usually treated with a combination of different drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

Keep this medicine in the foil pouch until you are ready to use it. Once a pouch is opened, you must use the medicine right away. Throw the empty pouch away where children and pets cannot get to it.

Store the foil pouches in the refrigerator but do not allow them to freeze.

You may store the foil pouches at room temperature but you must use them within 6 weeks. Store the single-use vials at room temperature and protect them from heat and light. Do not use any medicine if it does not look clear and colorless in the vial.

Side Effects Centers

Brovana Patient Information including If I Miss a Dose

What happens if I miss a dose (Brovana)?

Skip the missed dose and wait until your next regularly scheduled dose. Do not use two doses at the same time. It is important to use arformoterol inhalation regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

What happens if I overdose (Brovana)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of arformoterol inhalation can be fatal.

Overdose symptoms may include chest pain, fast or irregular heartbeats, nervousness, tremor, muscle cramps, feeling light-headed, and fainting.

What should I avoid while using arformoterol inhalation (Brovana)?

Do not use a second long-acting inhaled bronchodilator such as formoterol (Foradil, Perforomist, Symbicort) or salmeterol (Serevent, Advair) unless your doctor has told you to.

What other drugs will affect arformoterol inhalation (Brovana)?

Tell your doctor about all other medicines you use, especially:

  • aminophylline (Truphylline) or theophylline (Elixophyllin, Respbid, Slo-Bid, Theo-Dur, Uniphyl);
  • an antibiotic such as azithromycin (Zithromax), clarithromycin (Biaxin), erythromycin (E-Mycin, E.E.S., Erythrocin, Ery-Tab), or telithromycin (Ketek);
  • an antidepressant such as amitriptyline (Elavil, Etrafon), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Janimine, Tofranil), or nortriptyline (Pamelor);
  • a beta-blocker such as atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;
  • a diuretic (water pill) such as amiloride (Midamor, Moduretic), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Lopressor, Vasoretic, Zestoretic), spironolactone (Aldactazide, Aldactone), triamterene (Dyrenium, Maxzide, Dyazide), and others;
  • heart rhythm medicine such as amiodarone (Cordarone, Pacerone), dofetilide (Tikosyn), disopyramide (Norpace), procainamide (Procan, Pronestyl), or quinidine (Quin-G);
  • an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate);
  • narcotic medication such as fentanyl (Actiq, Duragesic, Ionsys), hydrocodone (Lortab, Vicodin), hydromorphone (Dilaudid), methadone (Dolophine, Methadose), morphine (Kadian, MS Contin), oxycodone (OxyContin, Percocet), propoxyphene (Darvocet, Darvon); or
  • steroids (prednisone and others).

This list is not complete and other drugs may interact with arformoterol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about arformoterol inhalation.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.05. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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