These Highlights Do Not Include All The Information Needed To Use Omidria ®

Risk Summary

There are no available data on Omidria use in pregnant women or animals to inform any drug-associated risks. Oral administration of ketorolac to rats during late gestation produced dystocia and increased pup mortality at a dose 740-times the plasma exposure at the recommended human ophthalmic dose (RHOD). Since human systemic exposure to Omidria following a lens replacement procedure is low [ see Clinical Pharmacology ( 12.3) ], the applicability of animal findings to the risk of Omidria in humans during pregnancy is unclear. Omidria should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Storage: Store at 20˚ to 25˚C (68˚ to 77˚F). Protect from light.

Systemic overdosage of phenylephrine may cause a rise in blood pressure. It may also cause headache, anxiety, nausea, vomiting, and ventricular arrhythmias. Supportive care is recommended.

Risk Summary

There are no available data on Omidria use in pregnant women or animals to inform

any drug-associated risks. Oral administration of ketorolac to rats during late

gestation produced dystocia and increased pup mortality at a dose 740-times the

plasma exposure at the recommended human ophthalmic dose (RHOD). Since

human systemic exposure to Omidria following a lens replacement procedure is low

(see Clinical Pharmacology (12.3)], the applicability of animal findings to the risk

of Omidria in humans during pregnancy is unclear. Omidria should be used during

pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Premature closure of the ductus arteriosus in the fetus has occurred with third

trimester use of oral and injectable NSAIDs. Ketorolac plasma concentrations are

detectable following ocular Omidria administration [see Clinical Pharmacology (12.3)].

The use of Omidria during late pregnancy should be avoided.

.Q.a1a

Animal Data

No well-controlled animal reproduction studies have been conducted with Omidria

or phenylephrine.

Ketorolac, administered during organogenesis, did not cause embryofetal abnormalities

or mortalities in rabbits or rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day,

respectively. These doses produced systemic exposure that is 1150 times and

4960 times the plasma exposure (based on Cma,c) at the RHOD, respectively. When

administered to rats during late gestation (after Day 17 of gestation) at oral doses

up to 1.5 mg/kg/day (740 times the plasma exposure at the RHOD), ketorolac

produced dystocia and increased pup mortality.

Omidria is a sterile aqueous solution, containing the α ₁-adrenergic receptor agonist phenylephrine HCl and the nonsteroidal anti-inflammatory ketorolac tromethamine, for addition to ocular irrigating solution.

The descriptions and structural formulae are:

Phenylephrine Hydrochloride Drug Substance:

Figure 1: Chemical Structure for Phenylephrine HCl

Ketorolac Tromethamine Drug Substance:

Figure 2: Chemical Structure for Ketorolac Tromethamine

Omidria is a clear, colorless to slightly yellow, sterile solution concentrate with a pH of approximately 6.3.

Each vial of Omidria contains:

Actives: phenylephrine hydrochloride 12.4 mg/mL equivalent to 10.16 mg/mL of phenylephrine and ketorolac tromethamine 4.24 mg/mL equivalent to 2.88 mg/mL of ketorolac.

Inactives: citric acid monohydrate; sodium citrate dihydrate; water for injection; may include sodium hydroxide and/or hydrochloric acid for pH adjustment.

The safety and effectiveness of Omidria have been established in the pediatric population from neonates to adolescents (birth to younger than 17 years). Use of Omidria in this population is supported by evidence from adequate and well-controlled studies of Omidria in adults with additional data from a single active-controlled safety study in pediatric patients up to 3 years old [see Clinical Studies ( 14)] .

No overall differences in safety were observed between pediatric and adult patients.

No overall differences in safety or effectiveness have been observed between elderly and adult patients.

Omidria is contraindicated in patients with a known hypersensitivity to any of its ingredients.

The most common reported adverse reactions (≥2%) are eye irritation, posterior capsule opacification, increased intraocular pressure, and anterior chamber inflammation. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Rayner Surgical Inc. at 1-877-0MIDRIA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

In a pharmacokinetic study evaluating Omidria, systemic exposure to both phenylephrine and ketorolac was low or undetectable.

A single-dose of Omidria as part of the irrigation solution was administered in 14 patients during lens replacement surgery. The volume of irrigation solution used during surgery ranged between 150 mL to 300 mL (median 212.5 mL). Detectable phenylephrine plasma concentrations were observed in one of 14 patients (range 1.2 to 1.4 ng/mL) during the first 2 hours after the initiation of Omidria administration. The observed phenylephrine plasma concentrations could not be distinguished from the preoperative administration of phenylephrine 2.5% ophthalmic solution prior to exposure to Omidria.

Ketorolac plasma concentrations were detected in 10 of 14 patients (range 1.0 to 4.2 ng/mL) during the first 8 hours after the initiation of Omidria administration. The maximum ketorolac concentration was 15 ng/mL at 24 hours after the initiation of Omidria administration, which may have been due to application of postoperative ketorolac ophthalmic solution.

Omidria ^® is added to an ocular irrigating solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain.

NDC 82604-600-04

OMIDRIA ^®

(phenylephrine and ketorolac intraocular solution)

1% / 0.3%

For Intraocular use.

Must Be Diluted.

Single-Patient vial

Sterile 4 mL

Quantity: 4

Rx Only

NDC 82604-600-00

OMIDRIA ®

(phenylephrine and ketorolac intraocular solution)

1% / 0.3%

For Intraocular use.

Must Be Diluted.

Single-Patient vial

Sterile 4 mL

Quantity: 1

Rx Only

The two active pharmaceutical ingredients (API) in Omidria, phenylephrine and ketorolac, act to maintain pupil size by preventing intraoperative miosis, and reducing postoperative pain.

Phenylephrine is an α ₁-adrenergic receptor agonist and, in the eye, acts as a mydriatic agent by contracting the radial muscle of the iris. Ketorolac is a nonsteroidal anti-inflammatory that inhibits both cyclooxygenase enzymes (COX-1 and COX-2), resulting in a decrease in tissue concentrations of prostaglandins to reduce pain due to surgical trauma. Ketorolac, by inhibiting prostaglandin synthesis secondary to ocular surgical insult or direct mechanical stimulation of the iris, also prevents surgically induced miosis.

Systemic exposure to phenylephrine can cause elevations in blood pressure ( 5.1).

Omidria must be diluted prior to intraocular use. For administration to patients undergoing cataract surgery or intraocular lens replacement, 4 mL of Omidria is diluted in 500 mL of ocular irrigating solution. Irrigation solution is to be used as needed for the surgical procedure for a single patient.

The storage period for the diluted product is not more than 4 hours at room temperature or 24 hours under refrigerated conditions.

Do not use if the solution is cloudy or if it contains particulate matter.

Systemic exposure to phenylephrine can cause elevations in blood pressure.

Omidria is an intraocular solution containing 10.16 mg/mL (1% w/v) of phenylephrine and 2.88 mg/mL (0.3% w/v) of ketorolac for use in a single patient.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Table 1 shows frequently reported ocular adverse reactions with an incidence of ≥ 2% of adult patients as seen in the combined clinical trial results from three randomized, placebo-controlled studies [see Clinical Studies ( 14)] .

In a safety study that enrolled 72 pediatric patients up to 3 years old, no overall difference in safety was observed between pediatric and adult patients.

Inform patients that they may experience sensitivity to light.

Rayner Surgical Inc.



Suite 102, 14335 NE 24 Street

Bellevue, WA 98007

© Rayner 2023

Patented product; see www.rayner.com/patents for further details.

OMIDRIA®and the OMIDRIA® Logo are registered trademarks of Rayner Surgical Inc.

640069

Omidria (phenylephrine and ketorolac intraocular solution) 1%/0.3% is supplied in a clear, 5-mL glass, single-patient-use vial containing 4 mL of sterile solution, for addition to ocular irrigating solution.

Omidria is supplied in a multi-pack containing:

4 vials : NDC 82604-600-04 or

1 vials: NDC 82604-600-00

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti- inflammatory drugs (NSAIDs). There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac in patien ts who either have a known hypersensitivity to aspirin/NSAIDs or a past medical history of asthma. Therefore, use Omidria with caution in individuals who have previously exhibited sensitivities to these drugs.

Risk Summary

There are no available data on Omidria use in pregnant women or animals to inform any drug-associated risks. Oral administration of ketorolac to rats during late gestation produced dystocia and increased pup mortality at a dose 740-times the plasma exposure at the recommended human ophthalmic dose (RHOD). Since human systemic exposure to Omidria following a lens replacement procedure is low [ see Clinical Pharmacology ( 12.3) ], the applicability of animal findings to the risk of Omidria in humans during pregnancy is unclear. Omidria should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Storage: Store at 20˚ to 25˚C (68˚ to 77˚F). Protect from light.

Systemic overdosage of phenylephrine may cause a rise in blood pressure. It may also cause headache, anxiety, nausea, vomiting, and ventricular arrhythmias. Supportive care is recommended.

Risk Summary

There are no available data on Omidria use in pregnant women or animals to inform

any drug-associated risks. Oral administration of ketorolac to rats during late

gestation produced dystocia and increased pup mortality at a dose 740-times the

plasma exposure at the recommended human ophthalmic dose (RHOD). Since

human systemic exposure to Omidria following a lens replacement procedure is low

(see Clinical Pharmacology (12.3)], the applicability of animal findings to the risk

of Omidria in humans during pregnancy is unclear. Omidria should be used during

pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Premature closure of the ductus arteriosus in the fetus has occurred with third

trimester use of oral and injectable NSAIDs. Ketorolac plasma concentrations are

detectable following ocular Omidria administration [see Clinical Pharmacology (12.3)].

The use of Omidria during late pregnancy should be avoided.

.Q.a1a

Animal Data

No well-controlled animal reproduction studies have been conducted with Omidria

or phenylephrine.

Ketorolac, administered during organogenesis, did not cause embryofetal abnormalities

or mortalities in rabbits or rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day,

respectively. These doses produced systemic exposure that is 1150 times and

4960 times the plasma exposure (based on Cma,c) at the RHOD, respectively. When

administered to rats during late gestation (after Day 17 of gestation) at oral doses

up to 1.5 mg/kg/day (740 times the plasma exposure at the RHOD), ketorolac

produced dystocia and increased pup mortality.

Omidria is a sterile aqueous solution, containing the α ₁-adrenergic receptor agonist phenylephrine HCl and the nonsteroidal anti-inflammatory ketorolac tromethamine, for addition to ocular irrigating solution.

The descriptions and structural formulae are:

Phenylephrine Hydrochloride Drug Substance:

Figure 1: Chemical Structure for Phenylephrine HCl

Ketorolac Tromethamine Drug Substance:

Figure 2: Chemical Structure for Ketorolac Tromethamine

Omidria is a clear, colorless to slightly yellow, sterile solution concentrate with a pH of approximately 6.3.

Each vial of Omidria contains:

Actives: phenylephrine hydrochloride 12.4 mg/mL equivalent to 10.16 mg/mL of phenylephrine and ketorolac tromethamine 4.24 mg/mL equivalent to 2.88 mg/mL of ketorolac.

Inactives: citric acid monohydrate; sodium citrate dihydrate; water for injection; may include sodium hydroxide and/or hydrochloric acid for pH adjustment.

The safety and effectiveness of Omidria have been established in the pediatric population from neonates to adolescents (birth to younger than 17 years). Use of Omidria in this population is supported by evidence from adequate and well-controlled studies of Omidria in adults with additional data from a single active-controlled safety study in pediatric patients up to 3 years old [see Clinical Studies ( 14)] .

No overall differences in safety were observed between pediatric and adult patients.

No overall differences in safety or effectiveness have been observed between elderly and adult patients.

Omidria is contraindicated in patients with a known hypersensitivity to any of its ingredients.

The most common reported adverse reactions (≥2%) are eye irritation, posterior capsule opacification, increased intraocular pressure, and anterior chamber inflammation. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Rayner Surgical Inc. at 1-877-0MIDRIA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

In a pharmacokinetic study evaluating Omidria, systemic exposure to both phenylephrine and ketorolac was low or undetectable.

A single-dose of Omidria as part of the irrigation solution was administered in 14 patients during lens replacement surgery. The volume of irrigation solution used during surgery ranged between 150 mL to 300 mL (median 212.5 mL). Detectable phenylephrine plasma concentrations were observed in one of 14 patients (range 1.2 to 1.4 ng/mL) during the first 2 hours after the initiation of Omidria administration. The observed phenylephrine plasma concentrations could not be distinguished from the preoperative administration of phenylephrine 2.5% ophthalmic solution prior to exposure to Omidria.

Ketorolac plasma concentrations were detected in 10 of 14 patients (range 1.0 to 4.2 ng/mL) during the first 8 hours after the initiation of Omidria administration. The maximum ketorolac concentration was 15 ng/mL at 24 hours after the initiation of Omidria administration, which may have been due to application of postoperative ketorolac ophthalmic solution.

Omidria ^® is added to an ocular irrigating solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain.

NDC 82604-600-04

OMIDRIA ^®

(phenylephrine and ketorolac intraocular solution)

1% / 0.3%

For Intraocular use.

Must Be Diluted.

Single-Patient vial

Sterile 4 mL

Quantity: 4

Rx Only

NDC 82604-600-00

OMIDRIA ®

(phenylephrine and ketorolac intraocular solution)

1% / 0.3%

For Intraocular use.

Must Be Diluted.

Single-Patient vial

Sterile 4 mL

Quantity: 1

Rx Only

The two active pharmaceutical ingredients (API) in Omidria, phenylephrine and ketorolac, act to maintain pupil size by preventing intraoperative miosis, and reducing postoperative pain.

Phenylephrine is an α ₁-adrenergic receptor agonist and, in the eye, acts as a mydriatic agent by contracting the radial muscle of the iris. Ketorolac is a nonsteroidal anti-inflammatory that inhibits both cyclooxygenase enzymes (COX-1 and COX-2), resulting in a decrease in tissue concentrations of prostaglandins to reduce pain due to surgical trauma. Ketorolac, by inhibiting prostaglandin synthesis secondary to ocular surgical insult or direct mechanical stimulation of the iris, also prevents surgically induced miosis.

Systemic exposure to phenylephrine can cause elevations in blood pressure ( 5.1).

Omidria must be diluted prior to intraocular use. For administration to patients undergoing cataract surgery or intraocular lens replacement, 4 mL of Omidria is diluted in 500 mL of ocular irrigating solution. Irrigation solution is to be used as needed for the surgical procedure for a single patient.

The storage period for the diluted product is not more than 4 hours at room temperature or 24 hours under refrigerated conditions.

Do not use if the solution is cloudy or if it contains particulate matter.

Systemic exposure to phenylephrine can cause elevations in blood pressure.

Omidria is an intraocular solution containing 10.16 mg/mL (1% w/v) of phenylephrine and 2.88 mg/mL (0.3% w/v) of ketorolac for use in a single patient.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Table 1 shows frequently reported ocular adverse reactions with an incidence of ≥ 2% of adult patients as seen in the combined clinical trial results from three randomized, placebo-controlled studies [see Clinical Studies ( 14)] .

In a safety study that enrolled 72 pediatric patients up to 3 years old, no overall difference in safety was observed between pediatric and adult patients.

Inform patients that they may experience sensitivity to light.

Rayner Surgical Inc.



Suite 102, 14335 NE 24 Street

Bellevue, WA 98007

© Rayner 2023

Patented product; see www.rayner.com/patents for further details.

OMIDRIA®and the OMIDRIA® Logo are registered trademarks of Rayner Surgical Inc.

640069

Omidria (phenylephrine and ketorolac intraocular solution) 1%/0.3% is supplied in a clear, 5-mL glass, single-patient-use vial containing 4 mL of sterile solution, for addition to ocular irrigating solution.

Omidria is supplied in a multi-pack containing:

4 vials : NDC 82604-600-04 or

1 vials: NDC 82604-600-00

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti- inflammatory drugs (NSAIDs). There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac in patien ts who either have a known hypersensitivity to aspirin/NSAIDs or a past medical history of asthma. Therefore, use Omidria with caution in individuals who have previously exhibited sensitivities to these drugs.