XIIDRA

Adverse Drug Reaction Overview The most common ocular adverse reactions were eye irritation (18%), eye pain (13%) and instillation site reactions (12%); the majority of ocular adverse reactions were mild and transient in nature. The most common non-ocular adverse reaction was dysgeusia (14%).

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. In 5 clinical studies of dry eye disease, 1401 subjects received at least 1 dose of lifitegrast (1287 of which received lifitegrast ophthalmic solution 5%).

The majority of subjects (84%) had 3 months of treatment exposure. 177 subjects were exposed to lifitegrast for >6 months and 170 subjects were exposed to lifitegrast for approximately 12 months. The lifitegrast population was predominantly female (77%) and white (84%).

8) 1 Patients from safety population received at least one dose of study treatment during the study trial. Long-Term Study A long-term randomized, double-masked and placebo-controlled safety study was conducted over the course of 12 months in 332 patients (262 subjects completed) with dry eye disease.

Patients were allowed to use artificial tears concomitantly. The safety profile observed in this long-term study was similar to that seen in the short-term 12-week studies. Post-Market Adverse Reactions The following adverse reactions have been identified during post-approval use of XIIDRA.

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. Serious adverse reactions identified in post-marketing hypersensitivity reports included anaphylactic reaction, swollen tongue, hypersensitivity, Type IV hypersensitivity reaction, asthma, dyspnoea, pharyngeal edema, respiratory distress, angioedema, conjunctivitis allergic, and dermatitis allergic.

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Immune Hypersensitivity reactions are possible with XIIDRA. Rarely, allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with post marketing reports for XIIDRA. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Driving and Operating Machinery XIIDRA may cause transient blurred vision at instillation. If patients experience blurred vision, they should be advised not to drive or operate machinery until their vision has cleared. Special Populations Pregnant Women There are no adequate and well-controlled studies of XIIDRA use in pregnant women.

In a reproductive toxicology study in rats, intravenous administration of lifitegrast from pre-mating through gestation day 17 resulted in an increase in incidence of pre-implantation loss and incidences of skeletal malformations. In a reproductive toxicity study in rabbits, intravenous administration of lifitegrast during organogenesis resulted in incidences of omphalocele.

Since human systemic exposure to lifitegrast following ocular administration at the recommended human ophthalmic dose (RHOD) is low, the applicability of animal findings to the risk of lifitegrast use in humans during pregnancy is unclear.

XIIDRA should be used with caution during pregnancy (see TOXICOLOGY, Reproductive and Developmental Toxicity). Nursing Women It is not known whether XIIDRA is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when XIIDRA is administered to a nursing woman.

Pediatrics The safety and efficacy of XIIDRA have not been established in pediatric patients. Geriatrics No overall differences in safety or effectiveness have been observed between elderly and younger patients. Page 5 of