Phenylephrine Hydrochloride

1 INDICATIONS AND USAGE Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% and 10% is indicated to dilate the pupil. Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% and 10% is an alpha-1 adrenergic receptor agonist indicated to dilate the pupil (1 ).

2 DOSAGE AND ADMINISTRATION For patients 1 year of age and older: ( 2.1 ) • Apply one drop of Phenylephrine Hydrochloride Ophthalmic Solution (2.5% or 10% strength) to conjunctival fornix at 3 to 5 minute intervals up to a maximum of 3 drops per eye. • To obtain a greater degree of mydriasis, use 10% strength For pediatric patients less than 1 year of age: ( 2.2 ) • Instill one drop of 2.5% strength to conjunctival fornix at 3 to 5 minute intervals up to a maximum of 3 drops per eye 2.1 General Dosing Recommendations In patients 1 year of age or greater, apply one drop of either phenylephrine hydrochloride ophthalmic solution 2.5% or 10% every 3 to 5 minutes to the conjunctival fornix as required up to a maximum of 3 drops per eye per day. In order to obtain a greater degree of mydriasis, phenylephrine hydrochloride ophthalmic solution 10% may be needed. 2.2 Dosing in Pediatric Patients Less Than 1 Year of Age In pediatric patients less than 1 year of age, one drop of phenylephrine hydrochloride ophthalmic solution 2.5% should be instilled at 3 to 5 minute intervals up to a maximum of 3 drops per eye.

3 DOSAGE FORMS AND STRENGTHS Phenylephrine hydrochloride ophthalmic solution, USP 2.5% is a clear, colorless to yellow solution and free of foreign matter, sterile topical ophthalmic solution containing phenylephrine hydrochloride 2.5%: each mL contains 25 mg of phenylephrine hydrochloride. Phenylephrine hydrochloride ophthalmic solution, USP 10% is a clear, colorless to yellow solution and free of foreign matter, sterile topical ophthalmic solution containing phenylephrine hydrochloride 10%.: each mL contains 100 mg of phenylephrine hydrochloride. Ophthalmic solution (sterile): ( 3 ) • 25 mg of phenylephrine hydrochloride in one mL of solution (2.5%) • 100 mg of phenylephrine hydrochloride in one mL of solution (10%)

4 CONTRAINDICATIONS • Phenylephrine Hydrochloride Ophthalmic Solution, USP 10% is contraindicated in patients with hypertension, or thyrotoxicosis. Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% should be used in these patients ( 4.1 ). • Phenylephrine Hydrochloride Ophthalmic Solution, USP 10% is contraindicated in pediatric patients less than 1 year of age due to the increased risk of systemic toxicity. Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% should be used in these patients ( 4.2 ). 4.1 Cardiac and Endocrine Disease Phenylephrine Hydrochloride Ophthalmic Solution, USP 10% is contraindicated in patients with hypertension, or thyrotoxicosis. Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% should be used in these patients. 4.2 Pediatric Patients Less Than 1 Year of Age Phenylephrine Hydrochloride Ophthalmic Solution, USP 10% is contraindicated in pediatric patients less than 1 year of age due to the increased risk of systemic toxicity. Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% should be used in these patients [See Dosage and Administration ( 2.2 )].

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Cardiovascular Effects [See Warnings and Precautions ( 5.2 )] Elevation in Blood Pressure [See Warnings and Precautions ( 5.3 )] The following adverse reactions have been identified following use of phenylephrine hydrochloride ophthalmic solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Ocular adverse reactions include eye pain and stinging on instillation, temporary blurred vision, and photophobia ( 6.1 ) Cardiovascular adverse reactions include increase in blood pressure, syncope, myocardial infarction, tachycardia, arrhythmia and subarachnoid hemorrhage ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy's Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Ocular Adverse Reactions Eye pain and stinging on instillation, temporary blurred vision and photophobia, and conjunctival sensitization may occur. 6.2 Systemic Adverse Reactions A marked increase in blood pressure has been reported particularly, but not limited to low weight premature neonates, infants and hypertensive patients. Cardiovascular effects which have been seen primarily in hypertensive patients following topical ocular use of phenylephrine hydrochloride ophthalmic solution 10% include marked increase in blood pressure, syncope, myocardial infarction, tachycardia, arrhythmia and subarachnoid hemorrhage [See Warnings and Precautions ( 5.2 and 5.3 )] .

7 DRUG INTERACTIONS • May exaggerate the adrenergic pressor response in patients taking atropine-like drugs ( 7.1 ). • May potentiate the cardiovascular depressant effects of potent inhalation anesthetic agents ( 7.1 ). 7.1 Agents That May Exaggerate Pressor Responses Concomitant use of phenylephrine and atropine may enhance the pressor effects and induce tachycardia in some patients. Phenylephrine may potentiate the cardiovascular depressant effects of some inhalation anesthetic agents.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Animal reproduction studies have not been conducted with topical phenylephrine. It is also not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% and 10% should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers It is not known whether this drug is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% and 10% is administered to a nursing woman. 8.4 Pediatric Use Phenylephrine Hydrochloride Ophthalmic Solution, USP 10% is contraindicated in pediatric patients less than 1 year of age. [See Contraindications (4.2) ] . 8.5 Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger adult patients.

12.1 Mechanism of Action Phenylephrine is an alpha-1 adrenergic receptor agonist used for dilation of the pupil due to its vasoconstrictor and mydriatic action. Phenylephrine possesses predominantly α-adrenergic effects. In the eye, phenylephrine acts locally as a potent vasoconstrictor and mydriatic, by constricting ophthalmic blood vessels and the radial muscle of the iris.

11 DESCRIPTION Phenylephrine Hydrochloride Ophthalmic Solution, USP is a sterile, clear, colorless to yellow solution and free of foreign matter, topical α-adrenergic agonist for ophthalmic use. The active ingredient is represented by the chemical structure Chemical Name: (R)-3-hydroxy-α[(methylamino)methyl] benzenemethanol hydrochloride. Molecular Formula: C 9 H 13 NO 2 . HCl Molecular Weight: 203.67 g/mol Each mL of Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% contains: ACTIVE: Phenylephrine Hydrochloride 25 mg (2.5%); INACTIVES: Sodium Phosphate Monobasic Anhydrous, Sodium Phosphate Dibasic Anhydrous, Water for Injection. Phosphoric Acid and/or Sodium Hydroxide may be added to adjust pH (4.0 to 7.0). The solution has a tonicity of 340 mOsm/kg; PRESERVATIVE: Benzalkonium Chloride 0.1 mg (0.01%). Each mL of Phenylephrine Hydrochloride Ophthalmic Solution, USP 10% contains: ACTIVE: Phenylephrine Hydrochloride 100 mg (10%); INACTIVES: Sodium Phosphate Monobasic Anhydrous, Sodium Phosphate Dibasic Anhydrous, Water for Injection. Phosphoric Acid and/or Sodium Hydroxide may be added to adjust pH (4.0 to 7.0). The solution has a tonicity of 985 mOsm/kg; PRESERVATIVE: Benzalkonium Chloride 0.1 mg (0.01%). phenylepherinehcl-spl-structure

10 OVERDOSAGE Overdosage of phenylephrine may cause a rapid rise in blood pressure. It may also cause headache, anxiety, nausea, and vomiting, and ventricular arrhythmias. Prompt injection of a rapidly acting alpha-adrenergic blocking agent such as phentolamine has been recommended.

16 HOW SUPPLIED/STORAGE AND HANDLING Phenylephrine hydrochloride ophthalmic solution, USP 2.5% is supplied as a clear, colorless to yellow colored sterile, aqueous, topical ophthalmic solution in an opaque, white low density polyethylene (LDPE) bottle with a natural LDPE dropper tip and red cap in the following sizes: NDC 70756-629-25 2 mL in 5 mL bottle NDC 70756-676-30 10 mL in 10 mL bottle NDC 70756-649-35 15 mL in 15 mL bottle Phenylephrine hydrochloride ophthalmic solution, USP 10% is supplied as a sterile, clear, colorless to yellow color, aqueous, topical ophthalmic solution in an opaque, white low density polyethylene (LDPE) bottle with a natural LDPE dropper tip and red cap in the following sizes: NDC 70756-614-30 5 mL in 10 mL bottle After opening, Phenylephrine Hydrochloride Ophthalmic Solution, USP can be use until the expiration date on the bottle. Storage: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Keep container tightly closed. Protect from light and excessive heat. Do not use if solution is brown or contains precipitate.