Principal Display Panel - 2 Ml Vial Pouch Carton

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 ) Important limitations of use: Formoterol Fumarate Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. ( 1.2 , 5.2 ) Formoterol Fumarate Inhalation Solution is not indicated to treat asthma. ( 1.2 )

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 20 mcg/ 2 mL is supplied as a 2 mL sterile clear, colorless solution for nebulization in 2.5 mL low-density polyethylene unit dose vials. Each vial is overwrapped in a foil pouch and supplied in cartons as listed below. Carton of 30 individually wrapped unit dose vials, NDC 42858-094-35 Carton of 60 individually wrapped unit dose vials, NDC 42858-094-62

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

Formoterol fumarate inhalation solution is supplied as 2 mL of formoterol fumarate inhalation solution packaged in a 2.5 mL single-use low-density polyethylene vial and overwrapped in a foil pouch. Each vial contains 2 mL of a clear, colorless solution composed of formoterol fumarate dihydrate, USP equivalent to 20 mcg of formoterol fumarate in an isotonic, sterile aqueous solution containing sodium chloride, pH adjusted to 5.0 with citric acid and sodium citrate. The active component of formoterol fumarate inhalation solution is formoterol fumarate dihydrate, USP, a racemate. Formoterol fumarate dihydrate is a beta 2 -adrenergic bronchodilator. Its chemical name is (±)-2'-Hydroxy-5'-[(R*)-1-hydroxy-2-[[(R*)-p-methoxy-α-methylphenethyl]amino] ethyl]formanilide fumarate (2:1) (salt), dihydrate; its structural formula is: Formoterol fumarate dihydrate, USP has a molecular weight of 840.91 and its empirical formula is (C 19 H 24 N 2 O 4 ) 2 ∙C 4 H 4 O 4 ∙2H 2 O. Formoterol fumarate dihydrate, USP is a white or almost white or slightly yellow powder, which is freely soluble in dimethyl sulphoxide and in acetic acid, soluble in methanol, slightly soluble in 2-propanol, very slightly soluble in water, practically insoluble in acetonitrile and in diethyl ether. Formoterol fumarate inhalation solution does not require dilution prior to administration by nebulization. Like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors and the nebulization system used and its performance. Using the PARI LC Plus ® nebulizer (with a facemask or mouthpiece) connected to a PRONEB ® Ultra compressor under in vitro conditions, the mean delivered dose from the mouthpiece was approximately 7.3 mcg (37% of label claim). The mean nebulizer flow rate was 4 LPM and the nebulization time was 9 minutes. Formoterol fumarate inhalation solution should be administered from a standard jet nebulizer at adequate flow rates via a facemask or mouthpiece.

Other adrenergic drugs may potentiate effect. Use with caution. ( 5.3 , 7.1 ) Xanthine derivatives, steroids, diuretics, or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. Use with caution. ( 5.7 , 7.2 , 7.3 ) MAO inhibitors, tricyclic antidepressants and drugs that prolong QTc interval may potentiate effect on the cardiovascular system. Use with extreme caution. ( 7.4 ) Beta-blockers may decrease effectiveness. Use with caution and only when medically necessary. ( 7.5 )

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Formoterol fumarate inhalation solution is not indicated for use in children. The safety and effectiveness of formoterol fumarate inhalation solution in pediatric patients have not been established. The pharmacokinetics of formoterol fumarate has not been studied in pediatric patients.

Of the 586 subjects who received formoterol fumarate inhalation solution in clinical studies, 284 were 65 years and over, while 89 were 75 years and over. Of the 123 subjects who received formoterol fumarate inhalation solution in the 12-week safety and efficacy trial, 48 (39%) were 65 years of age or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetics of formoterol fumarate inhalation solution has not been studied in elderly subjects.

The carcinogenic potential of formoterol fumarate has been evaluated in 2-year drinking water and dietary studies in both rats and mice. In rats, the incidence of ovarian leiomyomas was increased at doses of 15,000 mcg/kg and above in the drinking water study and at 20,000 mcg/kg in the dietary study (AUC exposure approximately 2,300 times human exposure at the maximum recommended daily inhalation dose), but not at dietary doses up to 5,000 mcg/kg (AUC exposure approximately 570 times human exposure at the maximum recommended daily inhalation dose). In the dietary study, the incidence of benign ovarian theca-cell tumors was increased at doses of 500 mcg/kg (AUC exposure was approximately 57 times human exposure at the maximum recommended daily inhalation dose) and above. This finding was not observed in the drinking water study, nor was it seen in mice (see below). In mice, the incidence of adrenal subcapsular adenomas and carcinomas was increased in males at doses of 69,000 mcg/kg (AUC exposure approximately 1000 times human exposure at the maximum recommended daily inhalation dose) and above in the drinking water study, but not at doses up to 50,000 mcg/kg (AUC exposure approximately 750 times human exposure at the maximum recommended daily inhalation dose) in the dietary study. The incidence of hepatocarcinomas was increased in the dietary study at doses of 20,000 and 50,000 mcg/kg in females (AUC exposures approximately 300 and 750 times human exposure at the maximum recommended daily inhalation dose, respectively) and 50,000 mcg/kg in males, but not at doses up to 5,000 mcg/kg (AUC exposure approximately 75 times human exposure at the maximum recommended daily inhalation dose). Also in the dietary study, the incidence of uterine leiomyomas and leiomyosarcomas was increased at doses of 2,000 mcg/kg (AUC exposure was approximately 30 times human exposure at the maximum recommended daily inhalation dose) and above. Increases in leiomyomas of the rodent female genital tract have been similarly demonstrated with other beta-agonist drugs. Formoterol fumarate was not mutagenic or clastogenic in the following tests: mutagenicity tests in bacterial and mammalian cells, chromosomal analyses in mammalian cells, unscheduled DNA synthesis repair tests in rat hepatocytes and human fibroblasts, transformation assay in mammalian fibroblasts and micronucleus tests in mice and rats. Reproduction studies in rats revealed no impairment of fertility at oral doses up to 3,000 mcg/kg (approximately 730 times the maximum recommended daily inhalation powder dose in humans on a mcg/m 2 basis).

Long-acting beta 2 -adrenergic agonists, such as formoterol fumarate, 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 [see WARNINGS AND PRECAUTIONS (5.1) ].

The expected signs and symptoms with overdosage of formoterol fumarate 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, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, and metabolic acidosis. As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of formoterol fumarate inhalation solution. Treatment of overdosage consists of discontinuation of formoterol fumarate 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 formoterol fumarate inhalation solution. Cardiac monitoring is recommended in cases of overdosage. For additional information about overdose treatment, call a poison control center (1-800-222-1222).

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac 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 [see DRUG INTERACTIONS, Xanthine Derivatives, Steroids, or Diuretics (7.2) ] .

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.

PATIENT INFORMATION Formoterol Fumarate (for-mot-e-rol) Inhalation Solution What is formoterol fumarate inhalation solution? Formoterol fumarate inhalation solution is a long-acting beta 2 adrenergic agonist (LABA) used to control the symptoms of COPD in adults with COPD. COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both. Formoterol fumarate inhalation solution is only for use with a nebulizer. LABA medicines such as formoterol fumarate inhalation solution help the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath. Formoterol fumarate inhalation solution is for long-term use and should be taken 2 times each day, to improve the symptoms of COPD for better breathing. Formoterol fumarate inhalation solution is not used to treat sudden symptoms of COPD. Formoterol fumarate is not for the treatment of asthma. It is not known if formoterol fumarate inhalation solution is safe and effective in people with asthma. Formoterol fumarate inhalation solution should not be used in children. It is not known if formoterol fumarate inhalation solution is safe and effective in children. Do not use formoterol fumarate inhalation solution if you have asthma. Before using formoterol fumarate inhalation solution tell your healthcare provider about all of your medical conditions, including if you: have heart problems have high blood pressure have diabetes have seizures have thyroid problems have liver problems are pregnant or plan to become pregnant. It is not known if the medicine formoterol in formoterol fumarate inhalation solution passes into breast milk and if it can harm your baby. are breastfeeding or plan to breastfeed. It is not known if the medicine formoterol in formoterol fumarate inhalation solution passes into breast milk and if it can harm your baby. Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Formoterol fumarate inhalation solution and certain other medicines may interact with each other. This may cause serious side effects. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist each time you get a new medicine. How should I use formoterol fumarate inhalation solution? Read the step-by-step instructions for using formoterol fumarate inhalation solution at the end of this Patient Information leaflet. Use formoterol fumarate inhalation solution exactly as prescribed. One unit dose vial of formoterol fumarate inhalation solution is one dose. The usual dose of formoterol fumarate inhalation solution is 1 unit dose vial, 2 times each day (morning and evening) breathed in through your nebulizer machine. The 2 doses should be about 12 hours apart. Do not use more than 2 vials of formoterol fumarate inhalation solution a day. Do not mix other medicines with formoterol fumarate inhalation solution in your nebulizer machine. If you miss a dose of formoterol fumarate inhalation solution, just skip that dose. Take your next dose at your usual time. Do not take 2 doses at one time. While you are using formoterol fumarate inhalation solution 2 times each day: do not use other medicines that contain a long-acting beta 2 -agonist (LABA) for any reason. do not use your short-acting beta 2 -agonist medicine on regular basis (four times a day). Formoterol fumarate inhalation solution does not relieve sudden symptoms of COPD. Always have a rescue inhaler medicine with you to treat sudden symptoms. If you do not have a rescue inhaler medicine, call your healthcare provider to have one prescribed for you. Do not stop using formoterol fumarate inhalation solution or other medicines to control or treat your COPD unless told to do so by your healthcare provider because your symptoms might get worse. Your healthcare provider will change your medicines as needed. Do not use formoterol fumarate inhalation solution: more often than prescribed, more medicine than prescribed for you, or with other LABA medicines Call your healthcare provider or get emergency medical care right away if your breathing problems worsen with formoterol fumarate inhalation solution, you need to use your rescue medicine more often than usual, or your rescue medicine does not work as well for you to relieve your symptoms. What are the possible side effects of formoterol fumarate inhalation solution? Formoterol fumarate inhalation solution can cause serious side effects, including: people with asthma who take long-acting beta 2 adrenergic agonist (LABA) medicines, such as formoterol fumarate inhalation solution, without also using a medicine called an inhaled corticosteroid, have an increased risk of serious problems from asthma, including being hospitalized, needing a tube placed in their airway to help them breathe, or death. Call your healthcare provider if breathing problems worsen over time while using formoterol fumarate inhalation solution. You may need a different treatment . Get emergency medical care if: breathing problems worsen quickly you use your rescue inhaler medicine, but it does not relieve your breathing problems COPD symptoms that get worse over time . If your COPD symptoms worsen over time, do not increase your dose of formoterol fumarate inhalation solution, instead call your healthcare provider. using too much of a LABA medicine may cause: chest pain fast and irregular heartbeat tremor increased blood pressure headache nervousness sudden shortness of breath immediately after use of formoterol fumarate inhalation solution . Sudden shortness of breath may be life-threatening. If you have sudden breathing problems immediately after inhaling your medicine, call your healthcare provider or go to nearest hospital emergency room right away. effects on your heart , including fast or irregular heartbeat, chest pain or increased blood pressure. changes in laboratory levels , including high levels of blood sugar (hyperglycemia) and low levels of potassium (hypokalemia), which may cause symptoms of muscle spasm, muscle weakness or abnormal heart rhythm. serious allergic reactions including rash, hives, swelling of the face, mouth, and tongue, and breathing problems . Call your healthcare provider or get emergency medical care if you get any symptoms of a serious allergic reaction. Common side effects of formoterol fumarate inhalation solution include: headache muscle cramps dizziness tremor nausea tiredness nervousness vomiting trouble sleeping dry mouth diarrhea Tell your healthcare provider if you get any side effect that bothers you or that does not go away. These are not all the possible side effects of formoterol fumarate inhalation solution. For more information, ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 . How should I store formoterol fumarate inhalation solution ? Store formoterol fumarate inhalation solution in a refrigerator between 36° to 46°F (2° to 8°C) in the protective foil pouch. Protect from light and heat. Do not open a sealed pouch until you are ready to use a dose of formoterol fumarate inhalation solution. After a sealed pouch is opened, formoterol fumarate inhalation solution must be used right away. Formoterol fumarate inhalation solution may be used directly from the refrigerator. Formoterol fumarate inhalation solution may also be stored at room temperature between 68ºF to 77ºF (20º to 25ºC) for up to 3 months (90 days). If stored at room temperature, discard formoterol fumarate inhalation solution if it is not used after 3 months or if past the expiration date, whichever is sooner. Space is provided on the packaging to record dispense date and use by date. Do not use formoterol fumarate inhalation solution after the expiration date provided on the foil pouch and vial. Formoterol fumarate inhalation solution should be colorless. Discard formoterol fumarate inhalation solution if it is not colorless. Keep formoterol fumarate inhalation solution and all medicines out of the reach of children. General information about the safe and effective use of formoterol fumarate inhalation solution. Medicines are sometimes prescribed for purposes that are not listed in a Patient Information leaflet. Do not use formoterol fumarate inhalation solution for a condition for which it was not prescribed. Do not give formoterol fumarate inhalation solution to other people, even if they have the same symptoms that you have. It may harm them. You can ask your health care provider or pharmacist for information about formoterol fumarate inhalation solution that is written for health professionals. What are the ingredients in formoterol fumarate inhalation solution? Active ingredient: formoterol Inactive ingredients: sodium chloride, citric acid and sodium citrate Manufactured by: Holopack Verpackungstechnik GmbH Bahnhofstr, Sulzbach-Laufen, 74429 Germany (DEU) Marketed by: Rhodes Pharmaceuticals Wilson, NC 27893 USA For more information, call Slayback Pharma LLC at 1-844-566-2505 This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 6/2023

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.

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 pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol, 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 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 formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Formoterol 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 with COPD is unknown.

Information on the pharmacokinetics of formoterol (dry powder and/or inhalation solution) in plasma and/or urine is available in healthy subjects as well as patients with chronic obstructive pulmonary disease after oral inhalation of doses at and above the therapeutic dose. Urinary excretion of unchanged formoterol was used as an indirect measure of systemic exposure. Plasma drug disposition data parallel urinary excretion, and the elimination half-lives calculated for urine and plasma are similar.

LABA as monotherapy (without inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. ( 5.1 ) Do not initiate Formoterol Fumarate Inhalation Solution in acutely deteriorating patients. ( 5.2 ) Do not use for relief of acute symptoms. Concomitant short-acting beta 2 -agonists can be used as needed for acute relief. ( 5.2 ) 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 , 5.5 ) Life-threatening paradoxical bronchospasm can occur. Discontinue Formoterol Fumarate Inhalation Solution immediately. ( 5.4 ) Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. ( 5.6 , 5.7 )

Storage and Handling:

Formoterol Fumarate Inhalation Solution 20 mcg/2 mL vial Rx only NDC 42858-094-35 Patient Information for Patients Enclosed Sterile Unit Dose Vials - Individually Wrapped - For Oral Inhalation Only EACH 2 mL VIAL CONTAINS: ACTIVE: Formoterol fumarate, USP. INACTIVES: Citric acid, Sodium citrate, Sodium chloride, and Water. CARTON CONTAINS: 30 individually wrapped 2 mL vials Rhodes

Instructions for Using Formoterol Fumarate Inhalation Solution Formoterol fumarate inhalation solution is used only in a standard jet nebulizer machine connected to an air compressor. Make sure you know how to use your nebulizer machine before you use it to breathe in formoterol fumarate inhalation solution or other medicines. Do not mix formoterol fumarate inhalation solution with other medicines in your nebulizer machine. Formoterol fumarate inhalation solution comes sealed in a foil pouch. Do not open a sealed pouch until you are ready to use a dose of formoterol fumarate inhalation solution. 1. Remove vial from the foil pouch. 2. Twist the cap completely off the vial and squeeze all the medicine into the nebulizer medicine cup (reservoir) (Figure 1). 3. Connect the nebulizer reservoir to the mouthpiece or facemask (Figure 2). 4. Connect the nebulizer to the compressor. 5. Sit in a comfortable, upright position. Place the mouthpiece in your mouth (Figure 3) or put on the facemask (Figure 4); and turn on the compressor. 6. Breathe as calmly, deeply and evenly as possible through your mouth until no more mist is formed in the nebulizer reservoir. The average nebulization time is 9 minutes. At this point, the treatment is finished. 7. Discard the formoterol fumarate inhalation solution container and top after use. 8. Clean the nebulizer (see manufacturer's instructions). Manufactured by: Holopack Verpackungstechnik GmbH Bahnhofstr, Sulzbach-Laufen, 74429 Germany (DEU) Marketed by: Rhodes Pharmaceuticals Wilson, NC 27893 USA This Instructions for Use has been approved by the U.S. Food and Drug Administration Revised: 6/2023

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 ) Important limitations of use: Formoterol Fumarate Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. ( 1.2 , 5.2 ) Formoterol Fumarate Inhalation Solution is not indicated to treat asthma. ( 1.2 )

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 20 mcg/ 2 mL is supplied as a 2 mL sterile clear, colorless solution for nebulization in 2.5 mL low-density polyethylene unit dose vials. Each vial is overwrapped in a foil pouch and supplied in cartons as listed below. Carton of 30 individually wrapped unit dose vials, NDC 42858-094-35 Carton of 60 individually wrapped unit dose vials, NDC 42858-094-62

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

Other adrenergic drugs may potentiate effect. Use with caution. ( 5.3 , 7.1 ) Xanthine derivatives, steroids, diuretics, or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. Use with caution. ( 5.7 , 7.2 , 7.3 ) MAO inhibitors, tricyclic antidepressants and drugs that prolong QTc interval may potentiate effect on the cardiovascular system. Use with extreme caution. ( 7.4 ) Beta-blockers may decrease effectiveness. Use with caution and only when medically necessary. ( 7.5 )

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Formoterol fumarate inhalation solution is not indicated for use in children. The safety and effectiveness of formoterol fumarate inhalation solution in pediatric patients have not been established. The pharmacokinetics of formoterol fumarate has not been studied in pediatric patients.

Of the 586 subjects who received formoterol fumarate inhalation solution in clinical studies, 284 were 65 years and over, while 89 were 75 years and over. Of the 123 subjects who received formoterol fumarate inhalation solution in the 12-week safety and efficacy trial, 48 (39%) were 65 years of age or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetics of formoterol fumarate inhalation solution has not been studied in elderly subjects.

The carcinogenic potential of formoterol fumarate has been evaluated in 2-year drinking water and dietary studies in both rats and mice. In rats, the incidence of ovarian leiomyomas was increased at doses of 15,000 mcg/kg and above in the drinking water study and at 20,000 mcg/kg in the dietary study (AUC exposure approximately 2,300 times human exposure at the maximum recommended daily inhalation dose), but not at dietary doses up to 5,000 mcg/kg (AUC exposure approximately 570 times human exposure at the maximum recommended daily inhalation dose). In the dietary study, the incidence of benign ovarian theca-cell tumors was increased at doses of 500 mcg/kg (AUC exposure was approximately 57 times human exposure at the maximum recommended daily inhalation dose) and above. This finding was not observed in the drinking water study, nor was it seen in mice (see below). In mice, the incidence of adrenal subcapsular adenomas and carcinomas was increased in males at doses of 69,000 mcg/kg (AUC exposure approximately 1000 times human exposure at the maximum recommended daily inhalation dose) and above in the drinking water study, but not at doses up to 50,000 mcg/kg (AUC exposure approximately 750 times human exposure at the maximum recommended daily inhalation dose) in the dietary study. The incidence of hepatocarcinomas was increased in the dietary study at doses of 20,000 and 50,000 mcg/kg in females (AUC exposures approximately 300 and 750 times human exposure at the maximum recommended daily inhalation dose, respectively) and 50,000 mcg/kg in males, but not at doses up to 5,000 mcg/kg (AUC exposure approximately 75 times human exposure at the maximum recommended daily inhalation dose). Also in the dietary study, the incidence of uterine leiomyomas and leiomyosarcomas was increased at doses of 2,000 mcg/kg (AUC exposure was approximately 30 times human exposure at the maximum recommended daily inhalation dose) and above. Increases in leiomyomas of the rodent female genital tract have been similarly demonstrated with other beta-agonist drugs. Formoterol fumarate was not mutagenic or clastogenic in the following tests: mutagenicity tests in bacterial and mammalian cells, chromosomal analyses in mammalian cells, unscheduled DNA synthesis repair tests in rat hepatocytes and human fibroblasts, transformation assay in mammalian fibroblasts and micronucleus tests in mice and rats. Reproduction studies in rats revealed no impairment of fertility at oral doses up to 3,000 mcg/kg (approximately 730 times the maximum recommended daily inhalation powder dose in humans on a mcg/m 2 basis).

Long-acting beta 2 -adrenergic agonists, such as formoterol fumarate, 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 [see WARNINGS AND PRECAUTIONS (5.1) ].

The expected signs and symptoms with overdosage of formoterol fumarate 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, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, and metabolic acidosis. As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of formoterol fumarate inhalation solution. Treatment of overdosage consists of discontinuation of formoterol fumarate 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 formoterol fumarate inhalation solution. Cardiac monitoring is recommended in cases of overdosage. For additional information about overdose treatment, call a poison control center (1-800-222-1222).

Formoterol fumarate inhalation solution is supplied as 2 mL of formoterol fumarate inhalation solution packaged in a 2.5 mL single-use low-density polyethylene vial and overwrapped in a foil pouch. Each vial contains 2 mL of a clear, colorless solution composed of formoterol fumarate dihydrate, USP equivalent to 20 mcg of formoterol fumarate in an isotonic, sterile aqueous solution containing sodium chloride, pH adjusted to 5.0 with citric acid and sodium citrate. The active component of formoterol fumarate inhalation solution is formoterol fumarate dihydrate, USP, a racemate. Formoterol fumarate dihydrate is a beta 2 -adrenergic bronchodilator. Its chemical name is (±)-2'-Hydroxy-5'-[(R*)-1-hydroxy-2-[[(R*)-p-methoxy-α-methylphenethyl]amino] ethyl]formanilide fumarate (2:1) (salt), dihydrate; its structural formula is: Formoterol fumarate dihydrate, USP has a molecular weight of 840.91 and its empirical formula is (C 19 H 24 N 2 O 4 ) 2 ∙C 4 H 4 O 4 ∙2H 2 O. Formoterol fumarate dihydrate, USP is a white or almost white or slightly yellow powder, which is freely soluble in dimethyl sulphoxide and in acetic acid, soluble in methanol, slightly soluble in 2-propanol, very slightly soluble in water, practically insoluble in acetonitrile and in diethyl ether. Formoterol fumarate inhalation solution does not require dilution prior to administration by nebulization. Like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors and the nebulization system used and its performance. Using the PARI LC Plus ® nebulizer (with a facemask or mouthpiece) connected to a PRONEB ® Ultra compressor under in vitro conditions, the mean delivered dose from the mouthpiece was approximately 7.3 mcg (37% of label claim). The mean nebulizer flow rate was 4 LPM and the nebulization time was 9 minutes. Formoterol fumarate inhalation solution should be administered from a standard jet nebulizer at adequate flow rates via a facemask or mouthpiece.

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac 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 [see DRUG INTERACTIONS, Xanthine Derivatives, Steroids, or Diuretics (7.2) ] .

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.

PATIENT INFORMATION Formoterol Fumarate (for-mot-e-rol) Inhalation Solution What is formoterol fumarate inhalation solution? Formoterol fumarate inhalation solution is a long-acting beta 2 adrenergic agonist (LABA) used to control the symptoms of COPD in adults with COPD. COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both. Formoterol fumarate inhalation solution is only for use with a nebulizer. LABA medicines such as formoterol fumarate inhalation solution help the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath. Formoterol fumarate inhalation solution is for long-term use and should be taken 2 times each day, to improve the symptoms of COPD for better breathing. Formoterol fumarate inhalation solution is not used to treat sudden symptoms of COPD. Formoterol fumarate is not for the treatment of asthma. It is not known if formoterol fumarate inhalation solution is safe and effective in people with asthma. Formoterol fumarate inhalation solution should not be used in children. It is not known if formoterol fumarate inhalation solution is safe and effective in children. Do not use formoterol fumarate inhalation solution if you have asthma. Before using formoterol fumarate inhalation solution tell your healthcare provider about all of your medical conditions, including if you: have heart problems have high blood pressure have diabetes have seizures have thyroid problems have liver problems are pregnant or plan to become pregnant. It is not known if the medicine formoterol in formoterol fumarate inhalation solution passes into breast milk and if it can harm your baby. are breastfeeding or plan to breastfeed. It is not known if the medicine formoterol in formoterol fumarate inhalation solution passes into breast milk and if it can harm your baby. Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Formoterol fumarate inhalation solution and certain other medicines may interact with each other. This may cause serious side effects. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist each time you get a new medicine. How should I use formoterol fumarate inhalation solution? Read the step-by-step instructions for using formoterol fumarate inhalation solution at the end of this Patient Information leaflet. Use formoterol fumarate inhalation solution exactly as prescribed. One unit dose vial of formoterol fumarate inhalation solution is one dose. The usual dose of formoterol fumarate inhalation solution is 1 unit dose vial, 2 times each day (morning and evening) breathed in through your nebulizer machine. The 2 doses should be about 12 hours apart. Do not use more than 2 vials of formoterol fumarate inhalation solution a day. Do not mix other medicines with formoterol fumarate inhalation solution in your nebulizer machine. If you miss a dose of formoterol fumarate inhalation solution, just skip that dose. Take your next dose at your usual time. Do not take 2 doses at one time. While you are using formoterol fumarate inhalation solution 2 times each day: do not use other medicines that contain a long-acting beta 2 -agonist (LABA) for any reason. do not use your short-acting beta 2 -agonist medicine on regular basis (four times a day). Formoterol fumarate inhalation solution does not relieve sudden symptoms of COPD. Always have a rescue inhaler medicine with you to treat sudden symptoms. If you do not have a rescue inhaler medicine, call your healthcare provider to have one prescribed for you. Do not stop using formoterol fumarate inhalation solution or other medicines to control or treat your COPD unless told to do so by your healthcare provider because your symptoms might get worse. Your healthcare provider will change your medicines as needed. Do not use formoterol fumarate inhalation solution: more often than prescribed, more medicine than prescribed for you, or with other LABA medicines Call your healthcare provider or get emergency medical care right away if your breathing problems worsen with formoterol fumarate inhalation solution, you need to use your rescue medicine more often than usual, or your rescue medicine does not work as well for you to relieve your symptoms. What are the possible side effects of formoterol fumarate inhalation solution? Formoterol fumarate inhalation solution can cause serious side effects, including: people with asthma who take long-acting beta 2 adrenergic agonist (LABA) medicines, such as formoterol fumarate inhalation solution, without also using a medicine called an inhaled corticosteroid, have an increased risk of serious problems from asthma, including being hospitalized, needing a tube placed in their airway to help them breathe, or death. Call your healthcare provider if breathing problems worsen over time while using formoterol fumarate inhalation solution. You may need a different treatment . Get emergency medical care if: breathing problems worsen quickly you use your rescue inhaler medicine, but it does not relieve your breathing problems COPD symptoms that get worse over time . If your COPD symptoms worsen over time, do not increase your dose of formoterol fumarate inhalation solution, instead call your healthcare provider. using too much of a LABA medicine may cause: chest pain fast and irregular heartbeat tremor increased blood pressure headache nervousness sudden shortness of breath immediately after use of formoterol fumarate inhalation solution . Sudden shortness of breath may be life-threatening. If you have sudden breathing problems immediately after inhaling your medicine, call your healthcare provider or go to nearest hospital emergency room right away. effects on your heart , including fast or irregular heartbeat, chest pain or increased blood pressure. changes in laboratory levels , including high levels of blood sugar (hyperglycemia) and low levels of potassium (hypokalemia), which may cause symptoms of muscle spasm, muscle weakness or abnormal heart rhythm. serious allergic reactions including rash, hives, swelling of the face, mouth, and tongue, and breathing problems . Call your healthcare provider or get emergency medical care if you get any symptoms of a serious allergic reaction. Common side effects of formoterol fumarate inhalation solution include: headache muscle cramps dizziness tremor nausea tiredness nervousness vomiting trouble sleeping dry mouth diarrhea Tell your healthcare provider if you get any side effect that bothers you or that does not go away. These are not all the possible side effects of formoterol fumarate inhalation solution. For more information, ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 . How should I store formoterol fumarate inhalation solution ? Store formoterol fumarate inhalation solution in a refrigerator between 36° to 46°F (2° to 8°C) in the protective foil pouch. Protect from light and heat. Do not open a sealed pouch until you are ready to use a dose of formoterol fumarate inhalation solution. After a sealed pouch is opened, formoterol fumarate inhalation solution must be used right away. Formoterol fumarate inhalation solution may be used directly from the refrigerator. Formoterol fumarate inhalation solution may also be stored at room temperature between 68ºF to 77ºF (20º to 25ºC) for up to 3 months (90 days). If stored at room temperature, discard formoterol fumarate inhalation solution if it is not used after 3 months or if past the expiration date, whichever is sooner. Space is provided on the packaging to record dispense date and use by date. Do not use formoterol fumarate inhalation solution after the expiration date provided on the foil pouch and vial. Formoterol fumarate inhalation solution should be colorless. Discard formoterol fumarate inhalation solution if it is not colorless. Keep formoterol fumarate inhalation solution and all medicines out of the reach of children. General information about the safe and effective use of formoterol fumarate inhalation solution. Medicines are sometimes prescribed for purposes that are not listed in a Patient Information leaflet. Do not use formoterol fumarate inhalation solution for a condition for which it was not prescribed. Do not give formoterol fumarate inhalation solution to other people, even if they have the same symptoms that you have. It may harm them. You can ask your health care provider or pharmacist for information about formoterol fumarate inhalation solution that is written for health professionals. What are the ingredients in formoterol fumarate inhalation solution? Active ingredient: formoterol Inactive ingredients: sodium chloride, citric acid and sodium citrate Manufactured by: Holopack Verpackungstechnik GmbH Bahnhofstr, Sulzbach-Laufen, 74429 Germany (DEU) Marketed by: Rhodes Pharmaceuticals Wilson, NC 27893 USA For more information, call Slayback Pharma LLC at 1-844-566-2505 This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 6/2023

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.

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 pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol, 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 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 formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Formoterol 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 with COPD is unknown.

Information on the pharmacokinetics of formoterol (dry powder and/or inhalation solution) in plasma and/or urine is available in healthy subjects as well as patients with chronic obstructive pulmonary disease after oral inhalation of doses at and above the therapeutic dose. Urinary excretion of unchanged formoterol was used as an indirect measure of systemic exposure. Plasma drug disposition data parallel urinary excretion, and the elimination half-lives calculated for urine and plasma are similar.

LABA as monotherapy (without inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. ( 5.1 ) Do not initiate Formoterol Fumarate Inhalation Solution in acutely deteriorating patients. ( 5.2 ) Do not use for relief of acute symptoms. Concomitant short-acting beta 2 -agonists can be used as needed for acute relief. ( 5.2 ) 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 , 5.5 ) Life-threatening paradoxical bronchospasm can occur. Discontinue Formoterol Fumarate Inhalation Solution immediately. ( 5.4 ) Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. ( 5.6 , 5.7 )

Storage and Handling:

Formoterol Fumarate Inhalation Solution 20 mcg/2 mL vial Rx only NDC 42858-094-35 Patient Information for Patients Enclosed Sterile Unit Dose Vials - Individually Wrapped - For Oral Inhalation Only EACH 2 mL VIAL CONTAINS: ACTIVE: Formoterol fumarate, USP. INACTIVES: Citric acid, Sodium citrate, Sodium chloride, and Water. CARTON CONTAINS: 30 individually wrapped 2 mL vials Rhodes

Instructions for Using Formoterol Fumarate Inhalation Solution Formoterol fumarate inhalation solution is used only in a standard jet nebulizer machine connected to an air compressor. Make sure you know how to use your nebulizer machine before you use it to breathe in formoterol fumarate inhalation solution or other medicines. Do not mix formoterol fumarate inhalation solution with other medicines in your nebulizer machine. Formoterol fumarate inhalation solution comes sealed in a foil pouch. Do not open a sealed pouch until you are ready to use a dose of formoterol fumarate inhalation solution. 1. Remove vial from the foil pouch. 2. Twist the cap completely off the vial and squeeze all the medicine into the nebulizer medicine cup (reservoir) (Figure 1). 3. Connect the nebulizer reservoir to the mouthpiece or facemask (Figure 2). 4. Connect the nebulizer to the compressor. 5. Sit in a comfortable, upright position. Place the mouthpiece in your mouth (Figure 3) or put on the facemask (Figure 4); and turn on the compressor. 6. Breathe as calmly, deeply and evenly as possible through your mouth until no more mist is formed in the nebulizer reservoir. The average nebulization time is 9 minutes. At this point, the treatment is finished. 7. Discard the formoterol fumarate inhalation solution container and top after use. 8. Clean the nebulizer (see manufacturer's instructions). Manufactured by: Holopack Verpackungstechnik GmbH Bahnhofstr, Sulzbach-Laufen, 74429 Germany (DEU) Marketed by: Rhodes Pharmaceuticals Wilson, NC 27893 USA This Instructions for Use has been approved by the U.S. Food and Drug Administration Revised: 6/2023