PROLENSA

Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Two multi-centre, randomized, double-masked, parallel-group and placebo (vehicle)-controlled, phase 3 studies of identical design (S00124 ER and S00124 WR) evaluated the efficacy and safety of PROLENSA as compared with vehicle in the treatment of ocular inflammation and pain associated with cataract surgery.

The safety analyses were conducted on the Safety population, which included all randomized subjects undergoing cataract surgery who received at least 1 dose of investigational product (IP). In the pooled studies, a total of 416 patients were randomized with 212 receiving PROLENSA alone and 204 receiving vehicle once daily beginning one day prior to surgery, continuing on the day of surgery, and through the first 14 days post-surgery.

8%). 6%). See Table 1. Some of the adverse events may have been the result of the cataract surgical procedure itself, rather than the investigational products. IOP measurements were performed at pre-specified time points during the study.

5%, n=5) but not thereafter. 9%) Note: Subjects who reported the same AE more than once were counted once for each higher level or preferred term.

Note:

An event was considered related to IP if the relationship was ‘possible’, ‘probable’, or ‘definite’. Incidence was defined as the number of subjects reporting an AE per the number of subjects in the safety population. 0%) reported adverse reactions following use of PROLENSA after cataract surgery included eye pain and anterior chamber inflammation.

0% were experienced more frequently in the placebo group than the bromfenac treatment group. The most commonly reported AEs with ophthalmic NSAIDs have been generally associated with the cataract surgery rather than the medication alone.

Less Common Clinical Trial Adverse Drug Reactions (<1%) Eye Disorders: conjunctival hyperemia, conjunctival oedema, corneal oedema, corneal abrasion, uveitis, increased lacrimation, eyelid oedema, photophobia, blurred vision. Abnormal Hematologic and Clinical Chemistry Findings No laboratory abnormalities were reported as adverse events in any of the clinical studies.

General There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti-inflammatory drugs (NSAIDs), including PROLENSA. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

PROLENSA contains sodium sulfite, which may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low.

Sulfite sensitivity is seen more frequently in asthmatic than in non- asthmatic people. Ophthalmologic Corneal Effects and keratitis Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation.

These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs, including PROLENSA, and should be closely monitored for corneal health. , dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening.

Topical NSAIDs should be used with caution in these patients. Post-marketing experience with topical NSAIDs also suggests that use more than 24 hours prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events.

Delayed Healing All topical NSAIDs may slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Rebound inflammatory effect (macular edema) Post-marketing experience indicates that in rare cases, upon withdrawal of PROLENSA, a flare- up of the inflammatory response, in the form of macular edema, due to the cataract operation may occur.