FULL PRESCRIBING INFORMATION - XOPENEX HFA

1 full PRESCRIBING INFORMATION :CONTENTS*1 INDICATIONS AND Bronchospasm2 DOSAGE AND Recommended Administration Information3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND Paradoxical Deterioration of Use of Anti-Inflammatory Cardiovascular Do Not Exceed Recommended Immediate Hypersensitivity Coexisting Hypokalemia6 ADVERSE Clinical Trials Experience Post-marketing Experience7 DRUG Monoamine Oxidase Inhibitorsor Tricyclic Antidepressants8 USE IN SPECIFIC Pediatric Geriatric Renal Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL Mechanism of Pharmacokinetics13 NONCLINICAL Carcinogenesis, Mutagenesis, Impairmentof Animal Toxicology and/or Pharmacology14 CLINICAL Bronchospasm Associated with Asthma16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATIONHIGHLIGHTS OF PRESCRIBING INFORMATIONT hese highlights do not include all the INFORMATION needed to useXOPENEX HFA safely and effectively.

2 See full PRESCRIBING informationfor XOPENEX HFA . XOPENEX HFA (levalbuterol tartrate) inhalation aerosol, for oral inhalation useInitial Approval: 1999 RECENT MAJOR CHANGES Dosage and Administration, Administration INFORMATION . ( )02/2017 INDICATIONS AND USAGE XOPENEX HFA is a beta2-adrenergic agonist indicated for the treatmentor prevention of bronchospasm in patients 4 years of age and older withreversible obstructive airway disease. ( )DOSAGE AND ADMINISTRATION For Oral Inhalation Only ( ) Adults and children 4 years of age and older: 2 inhalations repeated every4 to 6 hours; in some patients, 1 inhalation every 4 hours maybe sufficient. ( ) Prime XOPENEX HFA before using for the first time and when the inhalerhas not been used for more than 3 days. To prime XOPENEX HFA,release 4 sprays into the air away from the face. ( ) At least once a week, wash the actuator with warm water and let it air-drycompletely.

3 ( )DOSAGE FORMS AND STRENGTHSI nhalation Aerosol: Each actuation delivers 59 mcg of levalbuterol tartrate(equivalent to 45 mcg of levalbuterol free base) from the actuatormouthpiece. 15 g pressurized canister containing 200 actuations (3)CONTRAINDICATIONS Hypersensitivity to levalbuterol, racemic albuterol or any other component ofXOPENEX HFA Inhalation Aerosol. (4)WARNINGS AND PRECAUTIONS Life-threatening paradoxical bronchospasm may occur. DiscontinueXOPENEX HFA immediately and treat with alternative therapy. ( ) Need for more doses of XOPENEX HFA than usual may be a sign ofdeterioration of asthma and requires reevaluation of treatment. ( ) XOPENEX HFA is not a substitute for corticosteroids. ( ) Cardiovascular effects may occur. Consider discontinuation ofXOPENEX HFA if these effects occur. Use with caution in patients withunderlying cardiovascular disorders. ( ) Excessive use may be fatal.

4 Do not exceed recommended dose. ( ) Immediate hypersensitivity reactions may occur. DiscontinueXOPENEX HFA immediately. ( ) Hypokalemia and changes in blood glucose may occur. ( , )ADVERSE REACTIONS Most common adverse reactions ( 2% and > placebo) are accidental injury,bronchitis, dizziness, pain, pharyngitis, rhinitis, and vomiting. (6)To report SUSPECTED ADVERSE REACTIONS, contact Sunovion Pharmaceuticals Inc. at 1-877-737-7226 or FDA at INTERACTIONS Other short-acting sympathomimetic aerosol bronchodilators andadrenergic drugs: May potentiate effect. (7) Beta-blockers: May block bronchodilatory effects of beta-agonistsand produce severe bronchospasm. Patients with asthma should notnormally be treated with beta-blockers. ( ) Diuretics: May worsen electrocardiographic changes or hypokalemiaassociated with diuretics may worsen. Consider monitoring potassiumlevels.

5 ( ) Digoxin: May decrease serum digoxin levels. Consider monitoringdigoxin levels. ( ) Monoamine oxidase inhibitors (MAOs) or tricyclic antidepressants: Maypotentiate effect of albuterol on the cardiovascular system. Consideralternative therapy in patients taking MAO inhibitors or tricyclicantidepressants. ( )See 17 for PATIENT COUNSELING INFORMATION and FDA-approvedpatient : 02/2017* Sections or subsections omitted from the full PRESCRIBING INFORMATION are not PRESCRIBING INFORMATION 1 INDICATIONS AND BronchospasmXOPENEX HFA is indicated for the treatment or prevention ofbronchospasm in adults, adolescents, and children 4 years of age and olderwith reversible obstructive airway AND Recommended DosagesThe recommended dosage of XOPENEX HFA for adults and children 4 yearsof age and older is 2 inhalations (90 mcg of levalbuterol free base) repeatedevery 4 to 6 hours; in some patients, 1 inhalation (45 mcg of levalbuterol freebase) every 4 hours may be sufficient.

6 More frequent administration or alarger number of inhalations is not routinely a previously effective dosage regimen fails to provide the usual response,this may be a marker of destabilization of asthma and requires reevaluationof the patient and the treatment regimen, giving special consideration to thepossible need for anti-inflammatory treatment, , Administration InformationFor oral inhalation only Shake well before use. Avoid spraying in the eyes. Prime the inhaler before using for the first time and when the inhalerhas not been used for more than 3 days by releasing 4 test sprays intothe air, away from the face. To maintain proper use of XOPENEX HFA, it is critical to wash theactuator with warm water and air-dry thoroughly at least once a inhaler may cease to deliver levalbuterol tartrate if not properlycleaned and dried thoroughly. Keep the plastic actuator clean to preventmedication build-up and blockage.

7 If the actuator becomes blockedwith levalbuterol tartrate, wash the actuator to remove the blockage. The canister is fitted with a dose indicator, which indicates how manyinhalations remain. The dose indicator display will move after everytenth actuation. When nearing the end of the usable inhalations, thecolor behind the number in the dose indicator window changes to the inhaler when the dose indicator display window showszero, corresponding to the use of 200 FORMS AND STRENGTHSI nhalation aerosol: XOPENEX HFA is a pressurized, metered dose XOPENEX HFA 15 gram canister contains 200 metered actuations(or inhalations).Each canister is fitted with a dose indicator and is supplied with a blueplastic actuator mouthpiece and a red mouthpiece cap. After priming, eachactuation of the inhaler delivers 59 mcg of levalbuterol tartrate (equivalentto 45 mcg of levalbuterol free base) from the actuator HFA is contraindicated in patients with a history ofhypersensitivity to levalbuterol, racemic albuterol, or any other componentof XOPENEX HFA.

8 Reactions have included urticaria, angioedema, rash,bronchospasm, anaphylaxis, and oropharyngeal AND Paradoxical BronchospasmXOPENEX HFA can produce paradoxical bronchospasm, which maybe life-threatening. If paradoxical bronchospasm occurs, XOPENEX HFAshould be discontinued immediately and alternative therapy instituted. Itshould be recognized that paradoxical broncho spasm, when associatedwith inhaled formulations, frequently occurs with the first use of anew Deterioration of AsthmaAsthma may deteriorate acutely over a period of hours or chronicallyover several days or longer. If the patient needs more doses ofXOPENEX HFA than usual, this may be a marker of destabilization ofasthma and requires reevaluation of the patient and treatment regimen,giving special consideration to the possible need for anti-inflammatorytreatment, , Use of Anti-Inflammatory AgentsThe use of a beta-adrenergic agonist alone may not be adequate to controlasthma in many patients.

9 Early consideration should be given to addinganti-inflammatory agents, , corticosteroids, to the therapeutic Cardiovascular EffectsXOPENEX HFA, like other beta-adrenergic agonists, can produce clinicallysignificant cardiovascular effects in some patients, as measured by heartrate, blood pressure, and symptoms. Although such effects are uncommonafter administration of XOPENEX HFA at recommended doses, if theyoccur, the drug may need to be discontinued. In addition, beta-agonistshave been reported to produce electrocardiogram (ECG) changes, suchas flattening of the T-wave, prolongation of the QTc interval, and STsegment depression. The clinical significance of these findings is , XOPENEX HFA, like all sympathomimetic amines, should be usedwith caution in patients with cardiovascular disorders, especially coronaryinsufficiency, cardiac arrhythmias, and Do Not Exceed Recommended DoseFatalities have been reported in association with excessive use of inhaledsympatho mimetic drugs in patients with asthma.

10 The exact cause of deathis unknown, but cardiac arrest following an unexpected development of asevere acute asthmatic crisis and subsequent hypoxia is Immediate Hypersensitivity ReactionsImmediate hypersensitivity reactions may occur after administration ofracemic albuterol, as demonstrated by rare cases of urticaria, angioedema,rash, bronchospasm, anaphylaxis, and oropharyngeal edema. The potentialfor hypersensitivity must be considered in the clinical evaluation of patientswho experience immediate hypersensitivity reactions while receivingXOPENEX Coexisting ConditionsXOPENEX HFA, like all sympathomimetic amines, should be used withcaution in patients with cardiovascular disorders, especially coronaryinsufficiency, hypertension, and cardiac arrhythmias; in patients withconvulsive disorders, hyperthyroidism, or diabetes mellitus; and in patientswho are unusually responsive to sympathomimetic amines.