Tyrvaya

1 INDICATIONS AND USAGE TYRVAYA (varenicline solution) nasal spray is indicated for the treatment of the signs and symptoms of dry eye disease. TYRVAYA (varenicline solution) nasal spray is a cholinergic agonist indicated for the treatment of the signs and symptoms of dry eye disease.

2 DOSAGE AND ADMINISTRATION • One spray in each nostril twice daily (approximately 12 hours apart). • Prime with seven actuations before initial use. Re-prime with 1 actuation if not used for more than five days.

2.1Dosing Information Spray

TYRVAYA once in each nostril twice daily (approximately 12 hours apart). If a dose is missed, resume regular dosing at the next scheduled dose time.

2.2Priming Instructions Priming

: Prime TYRVAYA before initial use by pumping seven actuations into the air away from the face. When TYRVAYA has not been used for more than 5 days, re-prime with 1 spray into the air. Do not shake.

None None.

8.1Pregnancy Risk Summary There

are no available data on TYRVAYA use in pregnant women to inform any drug associated risks. In animal reproduction studies, varenicline did not produce malformations at clinically relevant doses. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US 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 Pregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. While no fetal structural abnormalities occurred in either species, maternal toxicity, characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (4864 times the MRHD on a mg/m 2 basis). In a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation.

Maternal toxicity, characterized by a decrease in body weight gain, was observed at 15 mg/kg/day (1216 times the MRHD on a mg/m 2 basis). Decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day.

The most common adverse reaction reported in 82% of patients was sneezing. Events that were reported in 5-16% of patients were cough, throat irritation, and instillation-site (nose) irritation. To report SUSPECTED ADVERSE REACTIONS, contact Oyster Point Pharma at 1-877-EYE-0123 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. In three clinical studies of dry eye disease conducted with varenicline solution nasal spray, 349 patients received at least 1 dose of TYRVAYA. The majority of patients had 31 days of treatment exposure, with a maximum exposure of 105 days. The most common adverse reactions reported in 82% of TYRVAYA treated patients was sneezing.

Other common adverse reactions that were reported in >5% of patients include cough (16%), throat irritation (13%), and instillation-site (nose) irritation (8%).