Formoterol Fumarate Inhalation Solution

Formoterol Fumarate 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 Maintenance Treatment of COPD

  Formoterol Fumarate Inhalation Solution is indicated for the 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.
  )
  

Important limitations of use:

• Formoterol Fumarate Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. (
  
  
  1.2 Important Limitations of Use

  Formoterol Fumarate Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease

  [see WARNINGS AND PRECAUTIONS (5.2)].

  Formoterol Fumarate Inhalation Solution is not indicated to treat asthma. The safety and effectiveness of Formoterol Fumarate Inhalation Solution in asthma have not been established.
  ,
  
  
  5.2 Deterioration of Disease and Acute Episodes

  Formoterol Fumarate Inhalation Solution should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. Formoterol Fumarate Inhalation Solution has not been studied in patients with acutely deteriorating COPD. The use of Formoterol Fumarate Inhalation Solution in this setting is inappropriate.

  Formoterol Fumarate Inhalation Solution should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Formoterol Fumarate Inhalation Solution has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled short-acting beta₂-agonist.

  When beginning Formoterol Fumarate 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. When prescribing Formoterol Fumarate Inhalation Solution, the healthcare provider should also prescribe an inhaled, short-acting beta₂-agonist and instruct the patient how it should be used. Increasing inhaled beta₂-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If Formoterol Fumarate 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 Formoterol Fumarate Inhalation Solution beyond the recommended 20 mcg twice daily dose is not appropriate in this situation.
  )
  
• Formoterol Fumarate Inhalation Solution is not indicated to treat asthma. (
  
  
  1.2 Important Limitations of Use

  Formoterol Fumarate Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease

  [see WARNINGS AND PRECAUTIONS (5.2)].

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

The recommended dose of Formoterol Fumarate Inhalation Solution is one 20 mcg unit-dose vial administered twice daily (morning and evening) by nebulization. A total daily dose greater than 40 mcg is not recommended.

Formoterol Fumarate Inhalation Solution should be administered by the orally inhaled route via a standard jet nebulizer connected to an air compressor. The safety and efficacy of Formoterol Fumarate Inhalation Solution have been established in clinical trials when administered using the PARI-LC Plus® nebulizer (with a facemask or mouthpiece) and the PRONEB® Ultra compressor. The safety and efficacy of Formoterol Fumarate Inhalation Solution delivered from non-compressor based nebulizer systems have not been established.

Formoterol Fumarate Inhalation Solution should always be stored in the foil pouch, and only removed IMMEDIATELY BEFORE USE. Contents of any partially used container should be discarded.

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 re-evaluated and additional therapeutic options should be considered.

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

Formoterol Fumarate Inhalation Solution is supplied as a sterile solution for nebulization in low-density polyethylene unit-dose vials. Each vial contains formoterol fumarate dihydrate, USP equivalent to 20 mcg/2 mL of formoterol fumarate.

There are limited available data with Formoterol Fumarate Inhalation Solution use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Beta-agonists may interfere with uterine contractility

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

• LABA as monotherapy (without inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. (
  
  
  5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death

  • The safety and efficacy of Formoterol Fumarate Inhalation Solution in patients with asthma have not been established. Formoterol Fumarate Inhalation Solution is not indicated for the treatment of asthma [
    see CONTRAINDICATIONS (4)
    ].
  • Use of long-acting beta₂-adrenergic agonists (LABA) as monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed‑dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.
    
    • A 28-week, placebo-controlled US study comparing the safety of another LABA (salmeterol) with placebo, each added to usual
    
    asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with
    
    salmeterol vs. 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). The increased risk of asthma-related death
    
    is considered a class effect of the long-acting beta2-adrenergic agonists, including Formoterol Fumarate Inhalation Solution.
    
    • No study adequate to determine whether the rate of asthma related death is increased in patients treated with Formoterol
    
    Fumarate Inhalation Solution has been conducted. Clinical studies with formoterol fumarate administered as a dry powder inhaler
    
    suggested a higher incidence of serious asthma exacerbations in patients who received formoterol than in those who received
    
    placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates
    
    between treatment groups.

  • Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
  )
  
• Do not initiate Formoterol Fumarate Inhalation Solution in acutely deteriorating patients. (
  
  
  5.2 Deterioration of Disease and Acute Episodes

  Formoterol Fumarate Inhalation Solution should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. Formoterol Fumarate Inhalation Solution has not been studied in patients with acutely deteriorating COPD. The use of Formoterol Fumarate Inhalation Solution in this setting is inappropriate.

  Formoterol Fumarate Inhalation Solution should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Formoterol Fumarate Inhalation Solution has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled short-acting beta₂-agonist.

  When beginning Formoterol Fumarate 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. When prescribing Formoterol Fumarate Inhalation Solution, the healthcare provider should also prescribe an inhaled, short-acting beta₂-agonist and instruct the patient how it should be used. Increasing inhaled beta₂-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If Formoterol Fumarate 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 Formoterol Fumarate Inhalation Solution beyond the recommended 20 mcg twice daily dose is not appropriate in this situation.
  )
  
• Do not use for relief of acute symptoms. Concomitant short-acting beta
  
  ₂-agonists can be used as needed for acute relief. (
  
  
  5.2 Deterioration of Disease and Acute Episodes

  Formoterol Fumarate Inhalation Solution should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. Formoterol Fumarate Inhalation Solution has not been studied in patients with acutely deteriorating COPD. The use of Formoterol Fumarate Inhalation Solution in this setting is inappropriate.

  Formoterol Fumarate Inhalation Solution should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Formoterol Fumarate Inhalation Solution has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled short-acting beta₂-agonist.

  When beginning Formoterol Fumarate 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. When prescribing Formoterol Fumarate Inhalation Solution, the healthcare provider should also prescribe an inhaled, short-acting beta₂-agonist and instruct the patient how it should be used. Increasing inhaled beta₂-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If Formoterol Fumarate 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 Formoterol Fumarate Inhalation Solution beyond the recommended 20 mcg twice daily dose is not appropriate in this situation.
  )
  
• Do not exceed the recommended dose. Excessive use of Formoterol Fumarate Inhalation Solution or use in conjunction with other medications containing long-acting beta
  
  ₂-agonists, can result in clinically significant cardiovascular effects, and may be fatal. (
  
  
  5.3 Excessive Use and Use with Other Long-Acting Beta₂-Agonists

  As with other inhaled beta₂-adrenergic drugs, Formoterol Fumarate Inhalation Solution should not be used more often, at higher doses than recommended, or in conjunction with other medications containing long-acting beta₂-agonists, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
  ,
  
  
  5.5 Cardiovascular Effects

  Formoterol Fumarate Inhalation Solution, like other beta₂-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic and/or diastolic blood pressure, and/or symptoms. If such effects occur, Formoterol Fumarate Inhalation Solution 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. Therefore, Formoterol Fumarate Inhalation Solution, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  )
  
• Life-threatening paradoxical bronchospasm can occur. Discontinue Formoterol Fumarate Inhalation Solution immediately. (
  
  
  5.4 Paradoxical Bronchospasm

  As with other inhaled beta₂-agonists, Formoterol Fumarate Inhalation Solution can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, Formoterol Fumarate Inhalation Solution should be discontinued immediately and alternative therapy instituted.
  )
  
• Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. (
  
  
  5.6 Coexisting Conditions

  Formoterol Fumarate Inhalation Solution, like other sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to sympathomimetic amines. Doses of the related beta₂-agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
  ,
  
  
  5.7 Hypokalemia and Hyperglycemia

  Beta-agonist medications may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects

  [see CLINICAL PHARMACOLOGY (12.2)].

  The decrease in serum potassium is usually transient, not requiring supplementation. Beta-agonist medications may produce transient hyperglycemia in some patients.

  Clinically significant changes in serum potassium and blood glucose were infrequent during clinical studies with long-term administration of Formoterol Fumarate Inhalation Solution at the recommended dose.
  )