QUZYTTIR

1 INDICATIONS AND USAGE QUZYTTIR ® is indicated for the treatment of acute urticaria in adults and children 6 months of age and older. QUZYTTIR ® is a histamine-1 (H 1 ) receptor antagonist indicated for the treatment of acute urticaria in adults and children 6 months of age and older ( 1 ) Limitations of Use : Not recommended in pediatric patients less than 6 years of age with impaired renal or hepatic function ( 1 ) Limitations of use: QUZYTTIR ® is not recommended in pediatric patients less than 6 years of age with impaired renal or hepatic function.

2 DOSAGE AND ADMINISTRATION QUZYTTIR is a single use injectable product for intravenous administration only. The recommended dosage regimen is once every 24 hours as needed for treatment of acute urticaria. Administer QUZYTTIR as an intravenous push over a period of 1 to 2 minutes. QUZYTTIR is not recommended in pediatric patients less than 6 years of age with impaired renal or hepatic function [see Pediatric Use ( 8.4 )]. If using as an antihistamine prior to infusion product administration, refer to infusion product prescribing information for instructions. For intravenous administration only ( 2 ) Recommended dosages: Adults and adolescents ≥ 12 years of age and older: 10 mg ( 2.1 ) Children 6 to 11 years: 5 mg or 10 mg ( 2.2 ) Children 6 months to 5 years: 2.5 mg ( 2.3 ) Recommended dosage regimen is once every 24 hours as needed for acute urticaria ( 2 ) 2.1 Adults and adolescents 12 years of age and older The recommended dosage is 10 mg administered by intravenous injection. 2.2 Children 6 to 11 years of age The recommended dosage is 5 mg or 10 mg depending on symptom severity administered by intravenous injection. 2.3 Children 6 months to 5 years of age The recommended dosage is 2.5 mg administered by intravenous injection.

4 CONTRAINDICATIONS The use of QUZYTTIR is contraindicated in patients with a known hypersensitivity to cetirizine hydrochloride or any of its ingredients, levocetirizine, or hydroxyzine. Known hypersensitivity to cetirizine hydrochloride or any of its ingredients, levocetirizine, or hydroxyzine ( 4 )

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.

7 DRUG INTERACTIONS No clinically significant drug interactions with oral cetirizine hydrochloride, the active ingredient in QUZYTTIR, have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin. There was a small decrease in the clearance of oral cetirizine hydrochloride caused by a 400-mg dose of theophylline; it is possible that larger theophylline doses could have a greater effect [see Clinical Pharmacology ( 12.3 )].

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 TerSera Therapeutics LLC at 1-844-334-4035 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.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women with cetirizine hydrochloride the active ingredient in QUZYTTIR. In animal reproduction studies, there was no evidence of fetal harm with administration of cetirizine hydrochloride by the oral route to pregnant mice, rats, and rabbits, during the period of organogenesis, at doses that were 45 times and higher than the maximum recommended human dose (MRHD) in adults. In rats treated during late gestation and the lactation period, cetirizine hydrochloride had no effects on pup development at oral doses up to approximately 30 times the MRHD in adults. In mice treated during late gestation and the lactation period, cetirizine hydrochloride administered by the oral route to the dams had no effects on pup development at a dose that was approximately 10 times the MRHD in adults; however, lower pup weight gain during lactation was observed at a dose that was 45 times the MRHD in adults (See Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20% respectively. Data Animal Data : In embryofetal development studies conducted in mice, rats, and rabbits, cetirizine hydrochloride, administered during the period of organogenesis, was not teratogenic at doses up to 45, 220, and 260 times the MRHD, respectively (on a mg/m 2 basis with maternal oral doses up to 96, 225, and 135 mg/kg). In a prenatal and postnatal development (PPND) study conducted in mice, cetirizine hydrochloride was administered at oral doses up to 96 mg/kg/day from gestation day 15 through lactation day 21. Cetirizine hydrochloride lowered pup body weight gain during lactation at an oral dose in dams that was approximately 45 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 96 mg/kg/day); however, there were no effects on pup weight gain at an oral dose in dams that was approximately 10 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 24 mg/kg/day). In a PPND study conducted in rats, cetirizine hydrochloride was administered at oral doses up to 180 mg/kg/day from gestation day 17 to lactation day 22. Cetirizine hydrochloride did not have any adverse effects on rat dams or offspring development at doses up to approximately 30 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 30 mg/kg/day). Cetirizine hydrochloride caused excessive maternal toxicity at an oral dose in dams that was approximately 180 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 180 mg/kg/day).