Lifitegrast

1 INDICATIONS AND USAGE Lifitegrast ophthalmic solution 5% is indicated for the treatment of the signs and symptoms of dry eye disease (DED). Lifitegrast ophthalmic solution 5% is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for the treatment of the signs and symptoms of dry eye disease (DED).

2 DOSAGE AND ADMINISTRATION Instill one drop of lifitegrast ophthalmic solution twice daily (approximately 12 hours apart) into each eye using a single-dose container. Discard the single-dose container immediately after using in each eye. Contact lenses should be removed prior to the administration of lifitegrast ophthalmic solution and may be reinserted 15 minutes following administration. One drop twice daily in each eye (approximately 12 hours apart).

4 CONTRAINDICATIONS Lifitegrast is contraindicated in patients with known hypersensitivity to lifitegrast or to any of the other ingredients in the formulation [see Adverse Reactions (6.2) ]. Hypersensitivity.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Hypersensitivity [see Contraindications (4) ] The most common adverse reactions (incidence 5% to 25%) following the use of lifitegrast were instillation-site irritation, dysgeusia and decreased visual acuity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc., at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov./medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In five clinical trials of DED conducted with lifitegrast ophthalmic solution, 1401 patients received at least one dose of lifitegrast (1287 of which received lifitegrast 5%). The majority of patients (84%) had less than or equal to 3 months of treatment exposure. One hundred-seventy patients were exposed to lifitegrast for approximately 12 months. The majority of the treated patients were female (77%). The most common adverse reactions reported in 5% to 25% of patients were instillation-site irritation, dysgeusia, and reduced visual acuity. Other adverse reactions reported in 1% to 5% of the patients were blurred vision, conjunctival hyperemia, eye irritation, headache, increased lacrimation, eye discharge, eye discomfort, eye pruritus, and sinusitis. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lifitegrast. 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. Rare serious cases of hypersensitivity, including anaphylactic reaction, bronchospasm, respiratory distress, pharyngeal edema, swollen tongue, urticaria, allergic conjunctivitis, dyspnea, angioedema, and allergic dermatitis have been reported. Eye swelling and rash have also been reported [see Contraindications (4) ].

8.1 Pregnancy Risk Summary There are no available data on lifitegrast use in pregnant women to inform any drug-associated risks. Intravenous (IV) administration of lifitegrast to pregnant rats, from premating through gestation day 17, did not produce teratogenicity at clinically relevant systemic exposures. Intravenous administration of lifitegrast to pregnant rabbits during organogenesis produced an increased incidence of omphalocele at the lowest dose tested, 3 mg/kg/day (400-fold the human plasma exposure at the recommended human ophthalmic dose [RHOD], based on the area under the curve [AUC] level). Since human systemic exposure to lifitegrast following ocular administration of lifitegrast at the RHOD is low, the applicability of animal findings to the risk of lifitegrast use in humans during pregnancy is unclear [see Clinical Pharmacology (12.3) ] . Data Animal Data Lifitegrast administered daily by IV injection to rats, from premating through gestation day 17, caused an increase in mean pre-implantation loss and an increased incidence of several minor skeletal anomalies at 30 mg/kg/day, representing 5,400-fold the human plasma exposure at the RHOD of lifitegrast, based on AUC. No teratogenicity was observed in the rat at 10 mg/kg/day (460-fold the human plasma exposure at the RHOD, based on AUC). In the rabbit, an increased incidence of omphalocele was observed at the lowest dose tested, 3 mg/kg/day (400-fold the human plasma exposure at the RHOD, based on AUC), when administered by IV injection daily from gestation days 7 through 19. A fetal no observed adverse effect level (NOAEL) was not identified in the rabbit.