OMIDRIA Solution for injection Ref.[10473] Active ingredients: Ketorolac Phenylephrine

5.1 Elevated Blood Pressure

Systemic exposure to phenylephrine can cause elevations in blood pressure.

5.2 Cross-Sensitivity or Hypersensitivity

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 patients 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.

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)].

Table 1. Ocular Adverse Reactions Reported by ≥2% of Adult Patients:

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.

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.

Data

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 C_max) 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.

Risk Summary

There are no data on the presence of Omidria in human milk, the effects on the breastfed infant, or the effects on milk production. Howerver, systemic exposure to Omidria, following a lens replacement procedure is low [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Omidria and any potential adverse effects on the breastfed child from Omidria.

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.