Perforomist

Product Type: HUMAN PRESCRIPTION DRUG

Route: RESPIRATORY (INHALATION)

Dosage Form:

NDC: 49502-605

Application: NDA022007

Effective: 20190531

1 INDICATIONS AND USAGE PERFOROMIST Inhalation Solution is a long-acting beta 2 -adrenergic agonist (beta 2 -agonist) indicated for: • Long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. ( 1.1 ) Important limitations of use: • PERFOROMIST Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. ( 1.2 , 5.2 ) • PERFOROMIST Inhalation Solution is not indicated to treat asthma. ( 1.2 ) 1.1 Maintenance Treatment of COPD PERFOROMIST (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. 1.2 Important Limitations of Use PERFOROMIST Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease [see WARNINGS AND PRECAUTIONS (5.2) ]. PERFOROMIST Inhalation Solution is not indicated to treat asthma. The safety and effectiveness of PERFOROMIST Inhalation Solution in asthma have not been established.

2 DOSAGE AND ADMINISTRATION The recommended dose of PERFOROMIST (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. PERFOROMIST 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 PERFOROMIST 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 PERFOROMIST Inhalation Solution delivered from non-compressor based nebulizer systems have not been established. PERFOROMIST 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 PERFOROMIST Inhalation Solution when mixed with other drugs in a nebulizer have not been established. For oral inhalation only. • One 20 mcg/2 mL vial every 12 hours ( 2 ) • For use with a standard jet nebulizer (with a facemask or mouthpiece) connected to an air compressor ( 2 )

4 CONTRAINDICATIONS Use of a LABA, including PERFOROMIST, without an inhaled corticosteroid is contraindicated in patients with asthma [see WARNINGS and PRECAUTIONS (5.1) ] . PERFOROMIST is not indicated for the treatment of asthma. • Use of a LABA, including PERFOROMIST, without an inhaled corticosteroid is contraindicated in patients with asthma. ( 4 )

Not available.

6 ADVERSE REACTIONS Long-acting beta 2 -adrenergic agonists, such as PERFOROMIST, as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of asthma-related events. PERFOROMIST is not indicated for the treatment of asthma [see WARNINGS AND PRECAUTIONS (5.1) ] . Most common adverse reactions ( > 2% and more common than placebo) are diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Beta 2 -Agonist Adverse Reaction Profile Adverse reactions to PERFOROMIST Inhalation Solution are expected to be similar in nature to other beta 2 -adrenergic receptor agonists including: angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, muscle cramps, palpitations, nausea, dizziness, fatigue, malaise, insomnia, hypokalemia, hyperglycemia, and metabolic acidosis. 6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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 practice. Adults with COPD The data described below reflect exposure to PERFOROMIST Inhalation Solution 20 mcg twice daily by oral inhalation in 586 patients, including 232 exposed for 6 months and 155 exposed for at least 1 year. PERFOROMIST Inhalation Solution was studied in a 12-week, placebo- and active-controlled trial (123 subjects treated with PERFOROMIST Inhalation Solution) and a 52-week, active-controlled trial (463 subjects treated with PERFOROMIST Inhalation Solution). Patients were mostly Caucasians (88%) between 40-90 years old (mean, 64 years old) and had COPD, with a mean FEV 1 of 1.33 L. Patients with significant concurrent cardiac and other medical diseases were excluded from the trials. Table 1 shows adverse reactions from the 12-week, double-blind, placebo-controlled trial where the frequency was greater than or equal to 2% in the PERFOROMIST Inhalation Solution group and where the rate in the PERFOROMIST Inhalation Solution group exceeded the rate in the placebo group. In this trial, the frequency of patients experiencing cardiovascular adverse events was 4.1% for PERFOROMIST Inhalation Solution and 4.4% for placebo. There were no frequently occurring specific cardiovascular adverse events for PERFOROMIST Inhalation Solution (frequency greater than or equal to 1% and greater than placebo). The rate of COPD exacerbations was 4.1% for PERFOROMIST Inhalation Solution and 7.9% for placebo. TABLE 1 Number of patients with adverse reactions in the 12-week multiple-dose controlled clinical trial Adverse Reaction PERFOROMIST Inhalation Solution 20 mcg Placebo n (%) n (%) Total Patients 123 (100) 114 (100) Diarrhea 6 (4.9) 4 (3.5) Nausea 6 (4.9) 3 (2.6) Nasopharyngitis 4 (3.3) 2 (1.8) Dry Mouth 4 (3.3) 2 (1.8) Vomiting 3 (2.4) 2 (1.8) Dizziness 3 (2.4) 1 (0.9) Insomnia 3 (2.4) 0 0 Patients treated with PERFOROMIST Inhalation Solution 20 mcg twice daily in the 52-week open-label trial did not experience an increase in specific clinically significant adverse events above the number expected based on the medical condition and age of the patients. 6.3 Postmarketing Experience The following adverse reactions have been reported during post-approval use of PERFOROMIST Inhalation Solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Anaphylactic reactions, urticaria, angioedema (presenting as face, lip, tongue, eye, pharyngeal, or mouth edema), rash, and bronchospasm