revefenacin 0.0583 MG/ML Inhalation Solution [Yupelri]

INDICATIONS AND USAGE YUPELRI is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). YUPELRI is an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) .

DOSAGE AND ADMINISTRATION The recommended dosage is 175 mcg YUPELRI (one 175 mcg unit‑dose vial) administered by oral inhalation once daily by nebulizer using a mouthpiece. Administration Overview YUPELRI should be administered by the orally inhaled route via a standard jet nebulizer connected to an air compressor (See Instructions for Use) . The safety and efficacy of YUPELRI have been established in clinical trials when administered using the PARI LC ® Sprint nebulizer with a mouthpiece and the PARI Trek ® S compressor. The safety and efficacy of YUPELRI delivered from non‑compressor based nebulizer systems have not been established. The YUPELRI unit-dose vial should only be removed from the foil pouch and opened IMMEDIATELY BEFORE USE. The vial and any residual content should be discarded after use. No dosage adjustment is required for geriatric patients, or patients with renal impairment [see Use in Specific Populations (8.5 , 8.7) and Clinical Pharmacology (12.3) ] . The drug compatibility (physical and chemical), efficacy, and safety of YUPELRI when mixed with other drugs in a nebulizer have not been established. For oral inhalation use only. Do not swallow YUPELRI. • One 175 mcg vial (3 mL) once daily. ( 2 ) • For use with a standard jet nebulizer with a mouthpiece connected to an air compressor. ( 2 )

WARNINGS AND PRECAUTIONS • Do not initiate YUPELRI in acutely deteriorating COPD or to treat acute symptoms. ( 5.1 ) • If paradoxical bronchospasm occurs, discontinue YUPELRI and institute alternative therapy. ( 5.2 ) • Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur. ( 5.3 ) • Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a healthcare provider immediately if symptoms occur. ( 5.4 ) • Immediate hypersensitivity reactions may occur. If such a reaction occurs, therapy with YUPELRI should be stopped at once and alternative treatments should be considered. ( 5.5 ) 5.1 Deterioration of Disease and Acute Episodes YUPELRI should not be initiated in patients during acutely deteriorating or potentially life-threatening episodes of COPD. YUPELRI has not been studied in subjects with acutely deteriorating COPD. The initiation of YUPELRI in this setting is not appropriate. YUPELRI is intended as a once-daily maintenance treatment for COPD and should not be used for relief of acute symptoms, i.e. as rescue therapy for the treatment of acute episodes of bronchospasm, and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta 2 -agonist. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If YUPELRI no longer controls symptoms of bronchoconstriction, the patient's inhaled, short-acting beta 2 -agonist becomes less effective, or the patient needs more inhalations of a short-acting beta 2 -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 dose of YUPELRI beyond the recommended dose is not appropriate in this situation. 5.2 Paradoxical Bronchospasm As with other inhaled medicines, YUPELRI can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with YUPELRI, it should be treated immediately with an inhaled, short-acting bronchodilator; YUPELRI should be discontinued immediately and alternative therapy should be instituted. 5.3 Worsening of Narrow-Angle Glaucoma YUPELRI should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g. eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately if any of these signs or symptoms develops. 5.4 Worsening of Urinary Retention YUPELRI should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g. difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develops. 5.5 Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions may occur after administration of YUPELRI. If such a reaction occurs, therapy with YUPELRI should be stopped at once and alternative treatments should be considered.

CONTRAINDICATIONS YUPELRI is contraindicated in patients with hypersensitivity to revefenacin or any component of this product. YUPELRI is contraindicated in patients with hypersensitivity to revefenacin or any component of this product. ( 4 )

Mechanism of Action Revefenacin is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of revefenacin is predominantly a site-specific effect.