Formoterol

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. Important limitations of use: • Formoterol fumarate inhalation solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. • Formoterol fumarate inhalation solution is not indicated to treat asthma.

Formoterol fumarate is a long-acting, beta 2 -adrenergic receptor agonist (beta 2 -agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors. Although beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects.

The 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.

Use of a LABA, including formoterol fumarate inhalation solution, without an inhaled corticosteroid is contraindicated in patients with asthma. Formoterol fumarate inhalation solution is not indicated for the treatment of asthma. • Use of a LABA, including formoterol fumarate inhalation solution, without an inhaled corticosteroid is contraindicated in patients with asthma.

• LABA as monotherapy (without inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. • Do not initiate formoterol fumarate inhalation solution in acutely deteriorating patients. • Do not use for relief of acute symptoms. Concomitant short-acting beta 2 -agonists can be used as needed for acute relief. • 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. • Life-threatening paradoxical bronchospasm can occur. Discontinue formoterol fumarate inhalation solution immediately. • Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs.

Long-acting beta 2 -adrenergic agonists, such as formoterol fumarate inhalation solution, as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of asthma-related events. Formoterol fumarate inhalation solution is not indicated for the treatment of asthma. Most common adverse reactions ( > 2% and more common than placebo) are diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia

• Other adrenergic drugs may potentiate effect. Use with caution. • Xanthine derivatives, steroids, diuretics, or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. Use with caution. • MAO inhibitors, tricyclic antidepressants and drugs that prolong QTc interval may potentiate effect on the cardiovascular system. Use with extreme caution. • Beta-blockers may decrease effectiveness. Use with caution and only when medically necessary.

Prior to dispensing to the patient: Store in a refrigerator, 2°C to 8°C (36°F to 46°F). After dispensing to the patient: Store in a refrigerator at 2°C to 8°C (36°F to 46°F) and discard when drug expires or store at room temperature, 20°C to 25°C (68°F to 77°F) and discard if not used after 3 months. Protect pouch from light and heat. • Formoterol fumarate inhalation solution should only be administered via a standard jet nebulizer connected to an air compressor with an adequate airflow and equipped with a facemask or mouthpiece. • Vial should always be stored in the foil pouch, and only removed IMMEDIATELY before use. • Do not take by mouth.