QUZYTTIR

5 WARNINGS AND PRECAUTIONS Somnolence/Sedation: Exercise caution when driving a car or operating potentially dangerous machinery ( 5.1 ) 5.1 Somnolence/Sedation In clinical trials with QUZYTTIR and cetirizine hydrochloride tablets, the occurrence of somnolence/sedation has been reported in some patients. Exercise due caution when driving a car or operating potentially dangerous machinery. Avoid concurrent use of QUZYTTIR with alcohol or other CNS depressants because additional reduction in alertness and additional impairment of CNS performance may occur.

6 ADVERSE REACTIONS The following clinically significant adverse reaction is described elsewhere in the labeling: Somnolence/Sedation [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (incidence less than 1%) with QUZYTTIR are dysgeusia, headache, paresthesia, presyncope, dyspepsia, feeling hot, and hyperhidrosis. Most common adverse reactions (incidence equal to or greater than 2%) with use of oral cetirizine hydrochloride are somnolence, fatigue, dry mouth, pharyngitis, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, call Esteve Pharmaceuticals, S.A. at 1-888-306-6259 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Oral cetirizine hydrochloride The following adverse reactions associated with the use of oral cetirizine hydrochloride were identified in clinical trials. In clinical trials in patients 12 years and older the most common adverse reactions to oral cetirizine hydrochloride occurring with a 2% or greater incidence and greater than placebo were somnolence (14%), fatigue (6%), dry mouth (5%), pharyngitis (2%), and dizziness (2%). In clinical trials in children 6 to 11 years of age with oral cetirizine hydrochloride the most common adverse reactions occurring with a 2% or greater incidence and greater than placebo were headache, pharyngitis, abdominal pain, coughing, somnolence, diarrhea, epistaxis, bronchospasm, nausea, and vomiting. Somnolence appeared to be dose related. Adverse reactions reported in placebo-controlled trials with oral cetirizine hydrochloride in pediatric patients 2 to 5 years were qualitatively similar in nature and generally similar in frequency to those reported in trials with children 6 to 11 years of age. In placebo-controlled trials of pediatric patients 6 to 24 months of age, the incidences of adverse experiences were similar in the oral cetirizine hydrochloride and placebo treatment groups in each trial. In a trial of 1 week duration in children 6 to 11 months of age patients who received oral cetirizine hydrochloride exhibited greater irritability/fussiness than patients on placebo. In a trial of 18 months duration in patients 12 months and older, insomnia occurred more frequently in patients who received oral cetirizine hydrochloride compared to patients who received placebo. QUZYTTIR The safety data of QUZYTTIR was evaluated in a randomized, double-blind, single-dose, non-inferiority study comparing QUZYTTIR to intravenous diphenhydramine in 262 adults with acute urticaria. The adverse reactions with QUZYTTIR occurred at an incidence of less than 1% and include: dyspepsia, feeling hot, dysgeusia, headache, paresthesia, presyncope, and hyperhidrosis. An additional randomized, double-blind, single dose study was conducted in 33 adults which showed similar safety results. Sedation Subject-rated sedation scores were assessed at baseline, 1 hr, and/or 2 hrs, and/or "Readiness for Discharge”. Sedation was rated on a 0 to 3 scale (0 = none, to 3 = severe) with lower sedation scores indicating less sedation. Subjects in the QUZYTTIR treatment group reported less sedation at all time points compared to subjects treated with diphenhydramine.