Ryzumvi

1 INDICATIONS AND USAGE Ryzumvi is indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. Ryzumvi is an alpha adrenergic blocker indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. ( 1 )

2 DOSAGE AND ADMINISTRATION Adults and Pediatric Patients Aged 12 Years or Older: Instill 1 or 2 drops in each dilated eye following the completion of the ophthalmic examination or procedure. If 2 drops are instilled, the second drop should be administered 5 minutes after the first drop. Pediatric Patients Aged 3 to 11 Years: Instill 1 drop in each dilated eye following the completion of the ophthalmic examination or procedure. One single-patient-use vial can be used to dose each dilated eye. Discard the single-patient-use vial immediately after use. • Adults and Pediatric Patients Aged 12 Years and Older: Instill 1 to 2 drops in each dilated eye following the completion of the ophthalmic examination or procedure to reverse mydriasis. ( 2 ) • Pediatric Patients Aged 3 to 11 Years: Instill 1 drop in each dilated eye following the completion of the ophthalmic examination or procedure to reverse mydriasis. ( 2 )

5 WARNINGS AND PRECAUTIONS Uveitis: Ryzumvi is not recommended to be used in patients with active ocular inflammation. ( 5.1 ) 5.1 Uveitis Ryzumvi is not recommended when active ocular inflammation (e.g., iritis) is present because adhesions (synechiae) may form between the iris and the lens. 5.2 Potential for Eye Injury or Contamination To avoid the potential for eye injury or contamination, care should be taken to avoid touching the vial tip to the eye or to any other surface. 5.3 Use with Contact Lenses Contact lens wearers should be advised to remove their lenses prior to the instillation of Ryzumvi and wait 10 minutes after dosing before reinserting their contact lenses.

4 CONTRAINDICATIONS None. None. ( 4 )

8.1 Pregnancy Risk Summary There are no available data with Ryzumvi administration in pregnant women to inform a drug-associated risk. In animal toxicology studies, when phentolamine was administered orally to pregnant mice and rats during the period of organogenesis, skeletal immaturity and decreased growth was observed in the offspring at doses at least 24-times the recommended clinical dose. Additionally, a lower rate of implantation was seen in pregnant rats treated with phentolamine administered at least 60-times the recommended clinical dose. No malformations or embryofetal deaths were observed in the offspring of pregnant mice, rats, and rabbits administered phentolamine during the period of organogenesis at doses of at least 24-, 60-, and 20-times, respectively, the recommended clinical dose (see Data ) . Ryzumvi should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Data Animal Data Oral administration of phentolamine to pregnant rats and mice at doses at least 24-times the recommended clinical dose (based on a body weight per surface area (mg/m 2 ) comparison with a 60-kg human) resulted in slightly decreased growth and slight skeletal immaturity of the fetuses. Immaturity was manifested by increased incidence of incomplete or unossified calcanei and phalangeal nuclei of the hind limb and of incompletely ossified sternebrae. At oral phentolamine doses at least 60-times the recommended clinical dose (based on a mg/m 2 comparison with a 60-kg human), a slightly lower rate of implantation was found in rats. Phentolamine did not affect embryonic or fetal development in rabbits at oral doses at least 20-times the recommended dose (based on a mg/m 2 comparison with a 60-kg human). No malformations or embryofetal deaths were observed in the rat, mouse or rabbit studies.

6 ADVERSE REACTIONS The most common adverse reactions that have been reported are instillation site discomfort (16%), conjunctival hyperemia (12%), and dysgeusia (6%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) 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. Ryzumvi was evaluated in 642 subjects in clinical trials across various subject populations. The most common ocular adverse reactions reported in > 5% of subjects were instillation site discomfort including pain, stinging, and burning (16%) and conjunctival hyperemia (12%). The only non-ocular adverse reaction reported in > 5% of subjects was dysgeusia (6%).