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1 INDICATIONS AND USAGE Bimatoprost ophthalmic solution 0.01% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. Bimatoprost ophthalmic solution 0.01% is a prostaglandin analog indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. (1)

2 DOSAGE AND ADMINISTRATION The recommended dosage is one drop in the affected eye(s) once daily in the evening. Bimatoprost ophthalmic solution 0.01% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours. Bimatoprost ophthalmic solution 0.01% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. One drop in the affected eye(s) once daily in the evening. (2)

4 CONTRAINDICATIONS Bimatoprost ophthalmic solution 0.01% is contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients [see Adverse Reactions (6.2)]. Hypersensitivity. (4)

5 WARNINGS AND PRECAUTIONS Pigmentation : Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. (5.1) Eyelash Changes : Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible. (5.2) 5.1 Pigmentation Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with bimatoprost ophthalmic solution 0.01% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. 5.2 Eyelash Changes Bimatoprost ophthalmic solution 0.01% may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment. 5.3 Intraocular Inflammation Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. In addition, because these products may exacerbate inflammation, caution should be used in patients with active intraocular inflammation (e.g., uveitis). 5.4 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. Bimatoprost ophthalmic solution 0.01% should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. 5.5 Bacterial Keratitis There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. 5.6 Contact Lens Use Bimatoprost ophthalmic solution 0.01% contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Contact lenses should be removed prior to instillation of bimatoprost ophthalmic solution 0.01% and may be reinserted 15 minutes following its administration.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Pigmentation including blepharal pigmentation and iris hyperpigmentation [see Warnings and Precautions (5.1)] Eyelash Changes [see Warnings and Precautions (5.2)] Intraocular Inflammation [see Warnings and Precautions (5.3)] Macular Edema [see Warnings and Precautions (5.4)] Hypersensitivity [see Contraindications (4)] Most common adverse reaction (31%) is conjunctival hyperemia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact First Nation Group, LLC at 1-855-221-5332 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 the 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 a 12-month clinical study with bimatoprost ophthalmic solutions 0.01%, the most common adverse reaction was conjunctival hyperemia (31%). Approximately 1.6% of patients discontinued therapy due to conjunctival hyperemia. Other adverse drug reactions (reported in 1 to 4% of patients) with bimatoprost ophthalmic solution 0.01% in this study included conjunctival edema, conjunctival hemorrhage, eye irritation, eye pain, eye pruritus, erythema of eyelid, eyelids pruritus, growth of eyelashes, hypertrichosis, instillation site irritation, punctate keratitis, skin hyperpigmentation, vision blurred, and visual acuity reduced. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of bimatoprost ophthalmic solution 0.01%. 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. These reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to bimatoprost ophthalmic solution, or a combination of these factors include: asthma-like symptoms, dizziness, dry eye, dyspnea, eye discharge, eye edema, foreign body sensation, headache, hypersensitivity including signs and symptoms of eye allergy and allergic dermatitis, hypertension, lacrimation increased, periorbital and lid changes associated with periorbital fat atrophy leading to skin tightness, deepening of the eyelid sulcus, eyelid ptosis, enophthalmos, and eyelid retraction; and photophobia.

8 USE IN SPECIFIC POPULATIONS Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. (8.4) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of bimatoprost ophthalmic solution 0.01% administration in pregnant women. There is no increase in the risk of major birth defects or miscarriages based on bimatoprost postmarketing experience. In embryofetal developmental studies, administraton of bimatoprost to pregnant mice and rats during organogenesis, resulted in abortion and early delivery at oral doses at least 33 times (mice) or 94 times (rats) the human exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood area under the curve [AUC] levels). These adverse effects were not observed at 2.6 times (mice) and 47 times (rats) the human exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood AUC levels). In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length and fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood AUC levels). No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood AUC levels). Because animal reproductive studies are not always predictive of human response bimatoprost ophthalmic solution 0.01% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data Animal Data In an embryofetal development rat study, abortion was observed in pregnant rats administered bimatoprost orally during organogenesis at 0.6 mg/kg/day (94 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 47 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC). No abnormalities were observed in rat fetuses at doses up to 0.6 mg/kg/day. In an embryofetal development mouse study, abortion and early delivery were observed in pregnant mice administered bimatoprost orally during organogenesis at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC). In a pre/postnatal development study, treatment of pregnant rats with bimatoprost orally from gestation day 7 to lactation day 20 resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC.

ed gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC. The NOAEL for postnatal development and mating performance of the offspring was 0.1 mg/kg/day (estimated at 14 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, based on AUC). 8.2 Lactation Risk Summary It is not known whether topical ocular treatment with bimatoprost ophthalmic solution 0.01% could result in sufficient systemic absorption to produce detectable quantities in human milk. In animal studies, bimatoprost has been shown to be present in breast milk of lactating rats at an intravenous dose (i.e., 1 mg/kg) 970 times the RHOD (on a mg/m 2 basis), however, no animal data is available at clinically relevant doses. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bimatoprost ophthalmic solution 0.01% and any potential adverse effects on the breastfed child from bimatoprost ophthalmic solution 0.01%. 8.4 Pediatric Use Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. 8.5 Geriatric Use No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

10 OVERDOSAGE No information is available on overdosage in humans. If overdose with bimatoprost ophthalmic solution 0.01% occurs, treatment should be symptomatic. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m 2 is at least 210 times higher than the accidental dose of one bottle of bimatoprost ophthalmic solution 0.01% for a 10 kg child.

11 DESCRIPTION Bimatoprost ophthalmic solution 0.01% is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is ( Z )-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-N-ethyl-5-heptenamide, and its molecular weight is 415.6. Its molecular formula is C 25 H 37 NO 4 . Its chemical structure is: Bimatoprost is a white or almost white crystalline powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. Bimatoprost ophthalmic solution 0.01% is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg. Bimatoprost ophthalmic solution 0.01% contains Active: bimatoprost 0.1 mg/mL; Preservative: benzalkonium chloride 0.2 mg/mL; Inactives: boric acid, glycerin, sodium borate, and water for injection. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8-7.8. structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. 12.3 Pharmacokinetics Absorption After one drop of bimatoprost ophthalmic solution 0.03% was administered once daily to both eyes of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/mL) in most subjects within 1.5 hours after dosing. Mean C max and AUC 0-24hr values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng•hr/mL, respectively, indicating that steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time. Distribution Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma. Elimination Metabolism Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites. Excretion Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage for 104 weeks at doses up to 2 mg/kg/day and 1 mg/kg/day, respectively (192 and 291 times the estimated human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, respectively, based on blood AUC levels) Mutagenesis Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Impairment of Fertility Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure to bimatoprost 0.03% dosed bilaterally once daily based on blood AUC levels).

14 CLINICAL STUDIES In a 12-month clinical study of patients with open angle glaucoma or ocular hypertension with an average baseline IOP of 23.5 mmHg, the IOP-lowering effect of bimatoprost ophthalmic solution 0.01% once daily (in the evening) was up to 7.5 mmHg.

16 HOW SUPPLIED/STORAGE AND HANDLING Bimatoprost ophthalmic solution 0.01% is supplied as sterile, clear, and colorless solution in opaque white high density polyethylene bottles with white low density polyethylene nozzle and high density polyethylene turquoise caps in the following sizes: 2.5 mL fill in a 10 mL container - NDC 81469-291-25 5 mL fill in a 10 mL container - NDC 81469-291-05 Storage: Store at 2°C to 25°C (36°F to 77°F). After opening, bimatoprost ophthalmic solution 0.01% can be used until the expiration date on the bottle.

17 PATIENT COUNSELING INFORMATION Potential for Pigmentation Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent. Also inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of bimatoprost ophthalmic solution 0.01%. Potential for Eyelash Changes Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with bimatoprost ophthalmic solution 0.01%. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment. Handling the Container Instruct patients to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. When to Seek Physician Advice Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice concerning the continued use of bimatoprost ophthalmic solution 0.01%. Contact Lens Use Advise patients that bimatoprost ophthalmic solution 0.01% contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of bimatoprost ophthalmic solution 0.01% and may be reinserted 15 minutes following its administration. Use with Other Ophthalmic Drugs Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes between applications. Manufactured for: First Nation Group, LLC 4566 E Highway 20 Suite #208 Niceville, FL 32578-8839 Product of Italy Revised: April 2026, V-01

1 INDICATIONS AND USAGE LATISSE ® (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. LATISSE ® is a prostaglandin analog, indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. ( 1 )

2 DOSAGE AND ADMINISTRATION Ensure the face is clean, makeup and contact lenses are removed. Once nightly, place one drop of LATISSE ® (bimatoprost ophthalmic solution) 0.03% on the disposable sterile applicator supplied with the package and apply evenly along the skin of the upper eyelid margin at the base of the eyelashes. The upper lid margin in the area of lash growth should feel lightly moist without runoff. Blot any excess solution runoff outside the upper eyelid margin with a tissue or other absorbent cloth. Dispose of the applicator after one use. Repeat for the opposite eyelid margin using a new sterile applicator. Do not reuse applicators and do not use any other brush/applicator to apply LATISSE ® . Do not apply to the lower eyelash line [see Warnings and Precautions ( 5.3 , 5.4 ) and Patient Counseling Information (17) ] . Additional applications of LATISSE ® will not increase the growth of eyelashes. Upon discontinuation of treatment, eyelash growth is expected to return to its pre-treatment level. Apply nightly directly to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying applicators. Blot any excess solution beyond the eyelid margin. Dispose of the applicator after one use. Repeat for the opposite eyelid margin using a new sterile applicator. ( 2 )

5 WARNINGS AND PRECAUTIONS Concurrent administration of LATISSE ® and intraocular pressure (IOP)-lowering prostaglandin analogs in ocular hypertensive patients may decrease the IOP-lowering effect. Patients using these products concomitantly should be closely monitored for changes to their IOP. ( 5.1 ) Pigmentation of the eyelids and iris may occur. Iris pigmentation is likely to be permanent. ( 5.2 , 5.3 ) 5.1 Effects on Intraocular Pressure Bimatoprost ophthalmic solution ( LUMIGAN ® ) lowers intraocular pressure (IOP) when instilled directly to the eye in patients with elevated IOP. In clinical trials, in patients with or without elevated IOP, LATISSE ® lowered IOP, however, the magnitude of the reduction was not cause for clinical concern. In ocular hypertension studies with LUMIGAN ® , it has been shown that exposure of the eye to more than one dose of bimatoprost daily may decrease the intraocular pressure lowering effect. In patients using LUMIGAN ® or other prostaglandin analogs for the treatment of elevated intraocular pressure, the concomitant use of LATISSE ® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN ® for IOP reduction should only use LATISSE ® after consulting with their physician and should be monitored for changes to their intraocular pressure. 5.2 Iris Pigmentation Increased iris pigmentation has occurred when bimatoprost solution was administered. Patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent [see Adverse Reactions (6.2) ] . The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. The long term effects of increased pigmentation are not known. Iris color changes seen with administration of bimatoprost ophthalmic solution may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. Treatment with LATISSE ® solution can be continued in patients who develop noticeably increased iris pigmentation. 5.3 Lid Pigmentation Bimatoprost has been reported to cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes. The pigmentation is expected to increase as long as bimatoprost is administered, but has been reported to be reversible upon discontinuation of bimatoprost in most patients. 5.4 Hair Growth Outside the Treatment Area There is the potential for hair growth to occur in areas where LATISSE ® solution comes in repeated contact with the skin surface. It is important to apply LATISSE ® only to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying sterile applicators, and to carefully blot any excess LATISSE ® from the eyelid margin to avoid it running onto the cheek or other skin areas. 5.5 Intraocular Inflammation LATISSE ® solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. 5.6 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution ( LUMIGAN ® ) for elevated IOP.

E ® solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. 5.6 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution ( LUMIGAN ® ) for elevated IOP. LATISSE ® should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. 5.7 Contamination of LATISSE ® or Applicators The LATISSE ® bottle must be kept intact during use. It is important to use LATISSE ® solution as instructed, by placing one drop on the single-use-per-eye applicator. The bottle tip should not be allowed to contact any other surface since it could become contaminated. The accompanying sterile applicators should only be used on one eye and then discarded since reuse of applicators increases the potential for contamination and infections. There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products [see Patient Counseling Information (17) ] . 5.8 Use with Contact Lenses LATISSE ® contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Contact lenses should be removed prior to application of solution and may be reinserted 15 minutes following its administration.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Effects on Intraocular Pressure [ see Warnings and Precautions (5.1) ] Iris Pigmentation [ see Warnings and Precautions (5.2) ] Lid Pigmentation [ see Warnings and Precautions (5.3) ] Hair Growth Outside the Treatment Area [ see Warnings and Precautions (5.4) ] Intraocular Inflammation [ see Warnings and Precautions (5.5) ] Macular Edema [ see Warnings and Precautions (5.6) ] Hypersensitivity [ see Contraindications (4) ] Most common adverse reactions (incidence approximately 3% to 4%) are eye pruritus, conjunctival hyperemia, and skin hyperpigmentation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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. The following information is based on clinical trial results from a multicenter, double-masked, randomized, vehicle-controlled, parallel study including 278 adult patients for four months of treatment. The most frequently reported adverse reactions were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and periorbital erythema. These reactions occurred in less than 4% of patients. Additional adverse reactions seen in clinical trials experience include foreign body sensation, hair growth abnormal, and iris hyperpigmentation. Additional adverse reactions reported with bimatoprost ophthalmic solution ( LUMIGAN ® ) for the reduction of intraocular pressure include, ocular dryness, visual disturbance, ocular burning, eye pain, blepharitis, cataract, superficial punctate keratitis, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, conjunctival edema, iritis, infections (primarily colds and upper respiratory tract infections), headaches, and asthenia. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of LATISSE ® . 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. The reactions include dry skin of the eyelid and/or periocular area, eye swelling, eyelid edema, hordeolum, hypersensitivity (local allergic reactions), lacrimation increased, madarosis and trichorrhexis (temporary loss of a few lashes to loss of sections of eyelashes, and temporary eyelash breakage, respectively), periorbital and lid changes associated with periorbital fat atrophy and skin tightness resulting in deepening of eyelid sulcus and eyelid ptosis, rash (including macular and erythematous), skin discoloration (periorbital), skin exfoliation of the eyelid and/or periorbital area, trichiasis, and vision blurred.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of LATISSE ® (bimatoprost ophthalmic solution) 0.03% administration in pregnant women. There is no increase in the risk of major birth defects or miscarriages based on bimatoprost postmarketing experience. In embryofetal development studies, administration of bimatoprost to pregnant mice and rats during organogenesis resulted in abortion and early delivery at oral doses at least 33 times (mice) or 94 times (rats) the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on the area under the curve (AUC). These adverse effects were not observed at 2.6 times (mice) and 47 times (rats) the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length and fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. Because animal reproductive studies are not always predictive of human response LATISSE ® 0.03% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data Animal Data In an embryofetal development rat study, abortion was observed in pregnant rats administered bimatoprost orally during organogenesis at 0.6 mg/kg/day (94 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 47 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on AUC). No abnormalities were observed in rat fetuses at doses up to 0.6 mg/kg/day. In an embryofetal development mouse study, abortion and early delivery were observed in pregnant mice administered bimatoprost orally during organogenesis at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC).

e cornea or conjunctival sac bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). In a pre/postnatal development study, treatment of pregnant rats with bimatoprost orally from gestation day 7 to lactation day 20 resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. The NOAEL for postnatal development and mating performance of the offspring was 0.1 mg/kg/day (estimated at 14 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). 8.2 Lactation Risk Summary It is not known whether topical ocular treatment with LATISSE ® 0.03% could result in sufficient systemic absorption to produce detectable quantities in human milk. In animal studies, bimatoprost has been shown to be present in breast milk of lactating rats at an intravenous dose (i.e., 1 mg/kg) 324 times the recommended human ophthalmic dose (on a mg/m 2 basis), however no animal data is available at clinically relevant doses. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LATISSE ® 0.03% and any potential adverse effects on the breastfed child from LATISSE ® 0.03%. 8.4 Pediatric Use Use of LATISSE ® was evaluated in a sixteen-week double-masked, randomized, vehicle-controlled study conducted in pediatric patients who were post-chemotherapy or had alopecia areata, and adolescents who had hypotrichosis with no associated medical condition. No new safety issues were observed. The results of the Global Eyelash Assessment (GEA) are provided in Table 1. Table 1. Number (%) of subjects with at least a 1-grade increase from baseline at month 4 in Global Eyelash Assessment Age Range (years) LATISSE ® Vehicle Difference (95% CI) Adolescents with hypotrichosis (N=40) 15 - 17 19/26 (73%) 1/14 (7%) 66% (44%, 88%) Post Chemotherapy Pediatric Patients (N=16) 5 - 17 11/13 (85%) 3/3 (100%) -15% (-35%, 4%) Alopecia Areata Pediatric Patients (N=15) 5 - 17 4/9 (44%) 2/6 (33%) 11% (-39%, 61%) 8.5 Geriatric Use No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

<table><caption>Table 1. Number (%) of subjects with at least a 1-grade increase from baseline at month 4 in Global Eyelash Assessment</caption><col width="222"/><col width="104"/><col width="124"/><col width="117"/><col width="167"/><tbody><tr><td styleCode="Toprule Lrule Rrule "> </td><td styleCode="Toprule Lrule Rrule " align="center">Age Range (years)</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">LATISSE</content><content styleCode="bold">^&#xAE;</content> </td><td styleCode="Toprule Lrule Rrule " align="center">Vehicle</td><td styleCode="Toprule Lrule Rrule " align="center">Difference (95% CI)</td></tr><tr><td styleCode="Toprule Lrule Rrule ">Adolescents with hypotrichosis (N=40)</td><td styleCode="Toprule Lrule Rrule " align="center">15 - 17</td><td styleCode="Toprule Lrule Rrule " align="center">19/26 (73%)</td><td styleCode="Toprule Lrule Rrule " align="center">1/14 (7%)</td><td styleCode="Toprule Lrule Rrule " align="center">66% (44%, 88%)</td></tr><tr><td styleCode="Toprule Lrule Rrule ">Post Chemotherapy Pediatric Patients (N=16)</td><td styleCode="Toprule Lrule Rrule " align="center">5 - 17</td><td styleCode="Toprule Lrule Rrule " align="center">11/13 (85%)</td><td styleCode="Toprule Lrule Rrule " align="center">3/3 (100%)</td><td styleCode="Toprule Lrule Rrule " align="center">-15% (-35%, 4%)</td></tr><tr><td styleCode="Toprule Lrule Rrule ">Alopecia Areata Pediatric Patients (N=15)</td><td styleCode="Toprule Lrule Rrule " align="center">5 - 17</td><td styleCode="Toprule Lrule Rrule " align="center">4/9 (44%)</td><td styleCode="Toprule Lrule Rrule " align="center">2/6 (33%)</td><td styleCode="Toprule Lrule Rrule " align="center">11% (-39%, 61%)</td></tr></tbody></table>

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of LATISSE ® (bimatoprost ophthalmic solution) 0.03% administration in pregnant women. There is no increase in the risk of major birth defects or miscarriages based on bimatoprost postmarketing experience. In embryofetal development studies, administration of bimatoprost to pregnant mice and rats during organogenesis resulted in abortion and early delivery at oral doses at least 33 times (mice) or 94 times (rats) the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on the area under the curve (AUC). These adverse effects were not observed at 2.6 times (mice) and 47 times (rats) the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length and fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. Because animal reproductive studies are not always predictive of human response LATISSE ® 0.03% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data Animal Data In an embryofetal development rat study, abortion was observed in pregnant rats administered bimatoprost orally during organogenesis at 0.6 mg/kg/day (94 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 47 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on AUC). No abnormalities were observed in rat fetuses at doses up to 0.6 mg/kg/day. In an embryofetal development mouse study, abortion and early delivery were observed in pregnant mice administered bimatoprost orally during organogenesis at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC).

e cornea or conjunctival sac bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). In a pre/postnatal development study, treatment of pregnant rats with bimatoprost orally from gestation day 7 to lactation day 20 resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. The NOAEL for postnatal development and mating performance of the offspring was 0.1 mg/kg/day (estimated at 14 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC).

8.4 Pediatric Use Use of LATISSE ® was evaluated in a sixteen-week double-masked, randomized, vehicle-controlled study conducted in pediatric patients who were post-chemotherapy or had alopecia areata, and adolescents who had hypotrichosis with no associated medical condition. No new safety issues were observed. The results of the Global Eyelash Assessment (GEA) are provided in Table 1. Table 1. Number (%) of subjects with at least a 1-grade increase from baseline at month 4 in Global Eyelash Assessment Age Range (years) LATISSE ® Vehicle Difference (95% CI) Adolescents with hypotrichosis (N=40) 15 - 17 19/26 (73%) 1/14 (7%) 66% (44%, 88%) Post Chemotherapy Pediatric Patients (N=16) 5 - 17 11/13 (85%) 3/3 (100%) -15% (-35%, 4%) Alopecia Areata Pediatric Patients (N=15) 5 - 17 4/9 (44%) 2/6 (33%) 11% (-39%, 61%)

11 DESCRIPTION LATISSE ® (bimatoprost ophthalmic solution) 0.03% is a synthetic prostaglandin analog. Its chemical name is ( Z )-7-[(1 R ,2 R ,3 R ,5 S )-3,5-Dihydroxy-2-[(1 E ,3 S )-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]- N -ethyl-5-heptenamide, and its molecular weight is 415.58. Its molecular formula is C 25 H 37 NO 4 . Its chemical structure is: Bimatoprost is a powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. LATISSE ® is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg. Contains: Active: bimatoprost 0.3 mg/mL; Preservative: benzalkonium chloride 0.05 mg/mL; Inactives: sodium chloride; sodium phosphate, dibasic; citric acid; and purified water. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8 - 7.8. chemical structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bimatoprost is a structural prostaglandin analog. Although the precise mechanism of action is unknown, the growth of eyelashes is believed to occur by increasing the percent of hairs in, and the duration of the anagen or growth phase. 12.3 Pharmacokinetics Absorption After one drop of bimatoprost ophthalmic solution 0.03% was administered once daily into both eyes (cornea and/or conjunctival sac) of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/mL) in most subjects within 1.5 hours after dosing. Mean C max and AUC 0-24hr values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng●hr/mL, respectively, indicating that steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time. Distribution Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma. Elimination Metabolism Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation. Bimatoprost then undergoes oxidation, N-deethylation, and glucuronidation to form a diverse variety of metabolites. Excretion Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.

12.1 Mechanism of Action Bimatoprost is a structural prostaglandin analog. Although the precise mechanism of action is unknown, the growth of eyelashes is believed to occur by increasing the percent of hairs in, and the duration of the anagen or growth phase.

12.3 Pharmacokinetics Absorption After one drop of bimatoprost ophthalmic solution 0.03% was administered once daily into both eyes (cornea and/or conjunctival sac) of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/mL) in most subjects within 1.5 hours after dosing. Mean C max and AUC 0-24hr values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng●hr/mL, respectively, indicating that steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time. Distribution Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma. Elimination Metabolism Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation. Bimatoprost then undergoes oxidation, N-deethylation, and glucuronidation to form a diverse variety of metabolites. Excretion Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage for 104 weeks at doses up to 2 mg/kg/day and 1 mg/kg/day, respectively (192 and 291 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on blood AUC levels). Mutagenesis Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Impairment of Fertility Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (103 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on blood AUC levels).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage for 104 weeks at doses up to 2 mg/kg/day and 1 mg/kg/day, respectively (192 and 291 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on blood AUC levels). Mutagenesis Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Impairment of Fertility Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (103 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on blood AUC levels).

14 CLINICAL STUDIES LATISSE ® solution was evaluated for its effect on overall eyelash prominence in a multicenter, double-masked, randomized, vehicle-controlled, parallel study including 278 adult patients for four months of treatment. The primary efficacy endpoint in this study was an increase in overall eyelash prominence as measured by at least a 1-grade increase on the 4-point Global Eyelash Assessment (GEA) scale, from baseline to the end of the treatment period (week 16). LATISSE ® was more effective than vehicle as measured by the GEA score, with statistically significant differences seen at 8-week, 12-week, and 16-week ( primary endpoint ) treatment durations. Table 2. Number (%) of subjects with at least a 1-grade increase from baseline in Global Eyelash Assessment (Primary Efficacy Endpoint – Week 16) Week LATISSE ® N=137 N (%) Vehicle N=141 N (%) 1 7 (5%) 3 (2%) 4 20 (15%) 11 (8%) 8 69 (50%) 21 (15%) 12 95 (69%) 28 (20%) 16 107 (78%) 26 (18%) 20 103 (79%) 27 (21%) In this study, patients were also evaluated for the effect of LATISSE ® solution on the length, thickness and darkness of their eyelashes. Improvements from baseline in eyelash growth as measured by digital image analysis assessing eyelash length, fullness/thickness, and darkness were statistically significantly more pronounced in the bimatoprost group at weeks 8, 12, and 16. Table 3 Efficacy endpoint at Week 16 (Mean Change from Baseline) LATISSE ® Vehicle Eyelash growth (length) (mm; % increase) N=137 1.4; 25% N=141 0.1; 2% Fullness/thickness (mm 2 ; % increase) N=136 0.7; 106% N=140 0.1; 12% Eyelash darkness (intensity*; % increase in darkness) N=135 -20.2; -18% N=138 -3.6; -3% * a negative value is representative of eyelash darkening After the 16-week treatment period, a 4-week post-treatment period followed during which the effects of bimatoprost started to return toward baseline. The effect on eyelash growth is expected to abate following longer term discontinuation.

<table><caption>Table 2. Number (%) of subjects with at least a 1-grade increase from baseline in Global Eyelash Assessment (Primary Efficacy Endpoint &#x2013; Week 16)</caption><col width="56"/><col width="122"/><col width="110"/><tbody><tr><td styleCode="Toprule Lrule Rrule " align="center">Week</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">LATISSE</content><content styleCode="bold">^&#xAE;</content> N=137 N (%)</td><td styleCode="Toprule Lrule Rrule " align="center">Vehicle N=141 N (%)</td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center">1</td><td styleCode="Toprule Lrule Rrule " align="center">7 (5%)</td><td styleCode="Toprule Lrule Rrule " align="center">3 (2%)</td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center">4</td><td styleCode="Toprule Lrule Rrule " align="center">20 (15%)</td><td styleCode="Toprule Lrule Rrule " align="center">11 (8%)</td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center">8</td><td styleCode="Toprule Lrule Rrule " align="center">69 (50%)</td><td styleCode="Toprule Lrule Rrule " align="center">21 (15%)</td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center">12</td><td styleCode="Toprule Lrule Rrule " align="center">95 (69%)</td><td styleCode="Toprule Lrule Rrule " align="center">28 (20%)</td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">16</content></td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">107 (78%)</content></td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">26 (18%)</content></td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center">20</td><td styleCode="Toprule Lrule Rrule " align="center">103 (79%)</td><td styleCode="Toprule Lrule Rrule " align="center">27 (21%)</td></tr></tbody></table>

td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">26 (18%)</content></td></tr><tr><td styleCode="Toprule Lrule Rrule " align="center">20</td><td styleCode="Toprule Lrule Rrule " align="center">103 (79%)</td><td styleCode="Toprule Lrule Rrule " align="center">27 (21%)</td></tr></tbody></table> <table><caption>Table 3</caption><col width="159"/><col width="94"/><col width="77"/><tbody><tr><td styleCode="Toprule Lrule Rrule ">Efficacy endpoint at Week 16 (Mean Change from Baseline)</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">LATISSE</content><content styleCode="bold">^&#xAE;</content> </td><td styleCode="Toprule Lrule Rrule " align="center">Vehicle </td></tr><tr><td styleCode="Toprule Lrule Rrule ">Eyelash growth (length) (mm; % increase)</td><td styleCode="Toprule Lrule Rrule " align="center">N=137 1.4; 25%</td><td styleCode="Toprule Lrule Rrule " align="center">N=141 0.1; 2% </td></tr><tr><td styleCode="Toprule Lrule Rrule ">Fullness/thickness (mm²; % increase)</td><td styleCode="Toprule Lrule Rrule " align="center">N=136 0.7; 106%</td><td styleCode="Toprule Lrule Rrule " align="center">N=140 0.1; 12%</td></tr><tr><td styleCode="Toprule Lrule Rrule ">Eyelash darkness (intensity*; % increase in darkness)</td><td styleCode="Toprule Lrule Rrule " align="center">N=135 -20.2; -18%</td><td styleCode="Toprule Lrule Rrule " align="center">N=138 -3.6; -3%</td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING LATISSE ® (bimatoprost ophthalmic solution) 0.03% is supplied sterile in opaque white low-density polyethylene dispenser bottles and tips with turquoise polystyrene caps accompanied by sterile, disposable applicators: 3 mL in a 5 mL bottle with 70 applicators NDC 0023-3616-70 5 mL in a 5 mL bottle with 140 applicators NDC 0023-3616-05 Storage: Store at 2º to 25ºC (36º to 77ºF).

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Nightly Application Inform patients that LATISSE ® (bimatoprost ophthalmic solution) should be applied every night using only the accompanying sterile applicators. They should start by ensuring their face is clean, all makeup is removed, and their contact lenses removed (if applicable). Then, carefully place one drop of LATISSE ® solution on the disposable sterile applicator and brush cautiously along the skin of the upper eyelid margin at the base of the eyelashes. If any LATISSE ® solution gets into the eye proper, it will not cause harm. The eye should not be rinsed. Additional applications of LATISSE ® will not increase the growth of eyelashes. Inform patients not to apply to the lower eyelash line. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material. The onset of effect is gradual but is not significant in the majority of patients until 2 months. Counsel patients that the effect is not permanent and can be expected to gradually return to the original level upon discontinuation of treatment with LATISSE ® . Handling the Bottle and Applicator Instruct patients that the LATISSE ® bottle must be maintained intact and to avoid allowing the tip of the bottle or applicator to contact surrounding structures, fingers, or any other unintended surface in order to avoid contamination of the bottle or applicator by common bacteria known to cause ocular infections. Instruct patients to only use the applicator supplied with the product once and then discard since reuse could result in using a contaminated applicator. Serious infections may result from using contaminated solutions or applicators. Potential for Intraocular Pressure Effects LATISSE ® may lower intraocular pressure although not to a level that will cause clinical harm. In patients using LUMIGAN ® or other prostaglandin analogs for the treatment of elevated intraocular pressure, the concomitant use of LATISSE ® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs for IOP reduction should only use LATISSE ® after consulting with their physician. Potential for Eyelid Skin Darkening Inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of LATISSE ® . Potential for Iris Darkening Advise patients about the potential for increased brown iris pigmentation which is likely to be permanent. Increased iris pigmentation has occurred when bimatoprost solution was administered. Potential for Unexpected Hair Growth or Eyelash Changes Inform patients of the possibility of hair growth occurring outside of the target treatment area if LATISSE ® repeatedly touches the same area of skin outside the treatment area. They should also be informed of the possibility of disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are likely reversible upon discontinuation of treatment. When to Seek Physician Advice Advise patients that if they develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of LATISSE ® .

hat if they develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of LATISSE ® . Patients on IOP-lowering medications should not use LATISSE ® without prior consultation with their physician. Contact Lens Use Advise patients that LATISSE ® solution contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Contact lenses should be removed prior to application of LATISSE ® and may be reinserted 15 minutes following its administration. Distributed by: AbbVie Inc. North Chicago, IL 60064 © 2024 AbbVie. All rights reserved. LATISSE and its design are trademarks of Allergan, Inc., an AbbVie company. v3.0USPI3616 ------Cut---Here--- ------------------------------------------------------------------------------------------------------------- abbvie logo Scissors

FDA-approved Patient Labeling PATIENT INFORMATION LATISSE ® [la teece] (bimatoprost ophthalmic solution) 0.03% Read the Patient Information that comes with LATISSE ® before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your physician about your treatment. What is hypotrichosis of the eyelashes? Hypotrichosis is another name for having inadequate or not enough eyelashes. What is LATISSE ® solution? LATISSE ® solution is a prescription treatment for hypotrichosis used to grow eyelashes, making them longer, thicker and darker. Who should NOT take LATISSE ® ? Do not use LATISSE ® solution if you are allergic to one of its ingredients. Are there any special warnings associated with LATISSE ® use? LATISSE ® solution is intended for use on the skin of the upper eyelid margins at the base of the eyelashes . Refer to Illustration 2 below. DO NOT APPLY to the lower eyelid. If you are using LUMIGAN ® or other products in the same class for elevated intraocular pressure (IOP), or if you have a history of abnormal IOP, you should only use LATISSE ® under the close supervision of your physician. LATISSE ® use may cause darkening of the eyelid skin which may be reversible. LATISSE ® use may also cause increased brown pigmentation of the colored part of the eye which is likely to be permanent. It is possible for hair growth to occur in other areas of your skin that LATISSE ® frequently touches. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material to reduce the chance of this from happening. It is also possible for a difference in eyelash length, thickness, fullness, pigmentation, number of eyelash hairs, and/or direction of eyelash growth to occur between eyes. These differences, should they occur, will usually go away if you stop using LATISSE ® . Who should I tell that I am using LATISSE ® ? You should tell your physician you are using LATISSE ® especially if you have a history of eye pressure problems. You should also tell anyone conducting an eye pressure screening that you are using LATISSE ® . What should I do if I get LATISSE ® in my eye? LATISSE ® solution is an ophthalmic drug product. LATISSE ® is not expected to cause harm if it gets into the eye proper. Do not attempt to rinse your eye in this situation. What are the possible side effects of LATISSE ® ? The most common side effects after using LATISSE ® solution are an itching sensation in the eyes and/or eye redness. This was reported in approximately 4% of patients. LATISSE ® solution may cause other less common side effects which typically occur on the skin close to where LATISSE ® is applied, or in the eyes. These include skin darkening, eye irritation, dryness of the eyes, and redness of the eyelids. If you develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, you should immediately seek your physician’s advice concerning the continued use of LATISSE ® solution. What happens if I stop using LATISSE ® ? If you stop using LATISSE ® , your eyelashes are expected to return to their previous appearance over several weeks to months. Any eyelid skin darkening is expected to reverse after several weeks to months.

r physician’s advice concerning the continued use of LATISSE ® solution. What happens if I stop using LATISSE ® ? If you stop using LATISSE ® , your eyelashes are expected to return to their previous appearance over several weeks to months. Any eyelid skin darkening is expected to reverse after several weeks to months. Any darkening of the colored part of the eye known as the iris is NOT expected to reverse and is likely permanent. How do I use LATISSE ® ? The recommended dosage is one application nightly to the skin of the upper eyelid margin at the base of the eyelashes only. Once nightly, start by ensuring your face is clean, makeup and contact lenses are removed. Remove an applicator from its tray. Then, holding the sterile applicator horizontally, place one drop of LATISSE ® on the area of the applicator closest to the tip but not on the tip (see Illustration 1). Then immediately draw the applicator carefully across the skin of the upper eyelid margin at the base of the eyelashes (where the eyelashes meet the skin) going from the inner part of your lash line to the outer part (see Illustration 2). Blot any excess solution beyond the eyelid margin. Dispose of the applicator after one use. Repeat for the opposite upper eyelid margin using a new sterile applicator. This helps minimize any potential for contamination from one eyelid to another. Illustration 1 Illustration 2 DO NOT APPLY in your eye or to the lower lid. ONLY use the sterile applicators supplied with LATISSE ® to apply the product. If you miss a dose, don’t try to “catch up.” Just apply LATISSE ® solution the next evening. Fifty percent of patients treated with LATISSE ® in a clinical study saw significant improvement by 2 months after starting treatment. If any LATISSE ® solution gets into the eye proper, it is not expected to cause harm. The eye should not be rinsed. Don’t allow the tip of the bottle or applicator to contact surrounding structures, fingers, or any other unintended surface in order to avoid contamination by common bacteria known to cause infections. Contact lenses should be removed prior to application of LATISSE ® and may be reinserted 15 minutes following its administration. Use of LATISSE ® more than once a day will not increase the growth of eyelashes more than use once a day. Store LATISSE ® solution at 36 o to 77 o F (2 o to 25 o C). General Information about LATISSE ® Prescription treatments are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use LATISSE ® solution for a condition for which it was not prescribed. Do not give LATISSE ® to other people. It may not be appropriate for them to use. This leaflet summarizes the most important information about LATISSE ® solution. If you would like more information, talk with your physician. You can also call AbbVie’s product information department at 1-800-678-1605. What are the ingredients in LATISSE ® ? Active ingredient: bimatoprost Inactive ingredients: benzalkonium chloride; sodium chloride; sodium phosphate, dibasic; citric acid; and purified water. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8 - 7.8. Distributed by: AbbVie Inc. North Chicago, IL 60064 © 2024 AbbVie. All rights reserved. LATISSE and its design are trademarks of Allergan, Inc., an AbbVie company. v2.0PPI3616 Latisse_dropApplication Latisse_application

1 INDICATIONS AND USAGE DURYSTA ® (bimatoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). DURYSTA is a prostaglandin analog indicated for the reduction of intraocular pressure (IOP) in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). ( 1 )

2 DOSAGE AND ADMINISTRATION For ophthalmic intracameral administration. ( 2.1 ) The intracameral administration should be carried out under standard aseptic conditions. ( 2.2 ) Figure 1 Figure 2 2. 1 General Information DURYSTA is an ophthalmic drug delivery system for a single intracameral administration of a biodegradable implant. DURYSTA should not be readministered to an eye that received a prior DURYSTA. 2.2 Administration The intracameral injection procedure must be performed under magnification that allows clear visualization of the anterior chamber structures and should be carried out using standard aseptic conditions for intracameral procedures, with the patient’s head in a stabilized position. The eye should not be dilated prior to the procedure. Remove the foil pouch from the carton and examine for damage. Then, open the foil pouch over a sterile field and gently drop the applicator on a sterile tray. Once the foil pouch is opened, use the applicator promptly. Figure 1 Perform a detailed visual inspection of the applicator, including ensuring that the actuator button has not been depressed, and the safety tab is in place. Carefully remove the plastic safety cap taking care to avoid contacting the needle tip. Inspect the needle tip for damage under magnification prior to use; the implant retention plug may be visible in the bevel and should not be removed. Prior to use, remove the safety tab by pulling it out perpendicular to the long axis of the applicator (refer to Figure 1a above). Do not twist or bend the tab. Stabilize the eye as the needle is advanced through the cornea. Enter the anterior chamber with the needle bevel visible through clear cornea. Enter parallel to the iris plane, adjacent to the limbus through clear cornea in the superotemporal quadrant. The needle should be inserted approximately 2 bevel lengths with the bevel completely within the anterior chamber; avoid positioning the needle bevel directly over the pupil. Ensure the needle is not bent before depressing the actuator button. See Figure 2. Figure 2 Depress the back half of the actuator button (refer to Figure 1b above) firmly until an audible and/or palpable click is noted. Following the release of the implant, remove the needle via the same track in which it was inserted and tamponade the opening. The implant should not be left in the corneal injection track. Check the injection site for leaks; make sure that it is self-sealing and the anterior chamber is formed. After injection, do not recap the needle. Dispose of the used applicator in a sharps disposal container and in accordance with local requirements. Instruct the patient to remain upright for at least 1 hour after the procedure so the implant can settle. Some degree of eye redness and discomfort is expected following administration. However, it is recommended to instruct patients that if the eye becomes progressively red, sensitive to light, painful, or develops a change in vision, they should immediately contact the physician.

4 CONTRAINDICATIONS Ocular or periocular infections ( 4.1 ) Corneal endothelial cell dystrophy ( 4.2 ) Prior corneal transplantation ( 4.3 ) Absent or ruptured posterior lens capsule ( 4.4 ) Hypersensitivity ( 4.5 ) 4.1 Ocular or Periocular Infections DURYSTA is contraindicated in patients with active or suspected ocular or periocular infections. 4.2 Corneal Endothelial Cell Dystrophy DURYSTA is contraindicated in patients with corneal endothelial cell dystrophy (e.g., Fuchs’ Dystrophy) [ see Warnings and Precautions ( 5.1 ) ] . 4.3 Prior Corneal Transplantation DURYSTA is contraindicated in patients with prior corneal transplantation, or endothelial cell transplants [e.g., Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)]. 4.4 Absent or Ruptured Posterior Lens Capsule DURYSTA is contraindicated in patients whose posterior lens capsule is absent or ruptured, due to the risk of implant migration into the posterior segment. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for DURYSTA use if the intraocular lens fully covers the opening in the posterior capsule. 4.5 Hypersensitivity DURYSTA is contraindicated in patients with hypersensitivity to bimatoprost or to any other components of the product [ see Adverse Reactions ( 6.1 ) ] .

5 WARNINGS AND PRECAUTIONS Endothelial cell loss : Due to possible corneal endothelial cell loss, administration of DURYSTA should be limited to a single implant per eye without retreatment. ( 5.1 ) Corneal Adverse Reactions : DURYSTA has been associated with corneal adverse reactions and risks are increased with multiple implants. Use caution in patients with limited corneal endothelial cell reserve. ( 5.1 ) Iridocorneal Angle : DURYSTA should be used with caution in patients with narrow angles or anatomical angle obstruction. ( 5.2 ) 5.1 Corneal Adverse Reactions The presence of DURYSTA implants has been associated with corneal adverse reactions and increased risk of corneal endothelial cell loss. Administration of DURYSTA should be limited to a single implant per eye without retreatment. Caution should be used when prescribing DURYSTA in patients with limited corneal endothelial cell reserve. 5.2 Iridocorneal Angle Following administration with DURYSTA, the intracameral implant is intended to settle within the inferior angle. DURYSTA should be used with caution in patients with narrow iridocorneal angles (Shaffer grade ˂ 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in the inferior angle. 5.3 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with ophthalmic bimatoprost, including DURYSTA intracameral implant. DURYSTA should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. 5.4 Intraocular Inflammation Prostaglandin analogs, including DURYSTA, have been reported to cause intraocular inflammation. DURYSTA should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. 5.5 Pigmentation Ophthalmic bimatoprost, including DURYSTA intracameral implant, has been reported to cause changes to pigmented tissues, such as increased pigmentation of the iris. Pigmentation of the iris is likely to be permanent. Patients who receive treatment should be informed of the possibility of increased pigmentation. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. While treatment with DURYSTA can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. 5.6 Endophthalmitis Intraocular surgical procedures and injections, including DURYSTA, have been associated with endophthalmitis. Proper aseptic technique must always be used with administering DURYSTA, and patients should be monitored following the administration.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Implant migration [see Contraindications ( 4.4 )] Hypersensitivity [ see Contraindications ( 4.5 ) ] Corneal adverse reactions [ see Warnings and Precautions ( 5.1 ) ] Macular edema [ see Warnings and Precautions ( 5.3 ) ] Intraocular inflammation [ see Warnings and Precautions ( 5.4 ) ] Pigmentation [ see Warnings and Precautions ( 5.5 ) ] Endophthalmitis [ see Warnings and Precautions ( 5.6 ) ] In controlled studies, the most common ocular adverse reaction reported by 27% of patients was conjunctival hyperemia. Other common adverse reactions reported in 5-10% of patients were foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, intraocular pressure increased, corneal endothelial cell loss, vision blurred, iritis, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 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 the 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. The most common ocular adverse reaction observed in two randomized, active-controlled clinical trials with DURYSTA in patients with OAG or OHT was conjunctival hyperemia, which was reported in 27% of patients. Other common ocular adverse reactions reported in 5-10% of patients were foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, intraocular pressure increased, corneal endothelial cell loss, vision blurred, and iritis. Ocular adverse reactions occurring in 1-5% of patients were anterior chamber cell, lacrimation increased, corneal edema, aqueous humor leakage, iris adhesions, ocular discomfort, corneal touch, iris hyperpigmentation, anterior chamber flare, anterior chamber inflammation, and macular edema. The following additional adverse drug reactions occurred in less than 1% of patients: hyphema, iridocyclitis, uveitis, corneal opacity, corneal thickening, product administered at inappropriate site, corneal decompensation, cystoid macular edema, and drug hypersensitivity. The most common nonocular adverse reaction was headache, which was observed in 5% of patients. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of DURYSTA. 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. Eye disorders : endophthalmitis

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of DURYSTA (bimatoprost intracameral implant) administration in pregnant women to inform a drug associated risk. Oral administration of bimatoprost to pregnant rats and mice throughout organogenesis did not produce adverse maternal or fetal effects at clinically relevant exposures. Oral administration of bimatoprost to rats from the start of organogenesis to the end of lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant exposures [see Animal Data] . Data Animal Data In an embryofetal development rat study, oral administration of bimatoprost to pregnant rats during organogenesis produced abortion at 0.6 mg/kg/day (1770-times the human systemic exposure to bimatoprost from DURYSTA, based on C max and a blood-to plasma partition ratio of 0.858). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 470-times the human systemic exposure to bimatoprost from DURYSTA, based on C max ). No fetal abnormalities were observed at doses up to 0.6 mg/kg/day. In an embryofetal development mouse study, oral administration of bimatoprost to pregnant mice during organogenesis produced abortion and early delivery at 0.3 mg/kg/day (2240-times the human systemic exposure to bimatoprost from DURYSTA, based on plasma C max level; blood-to plasma partition ratio of 0.858). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (400-times the human systemic exposure to bimatoprost from DURYSTA, based on C max ). No fetal abnormalities were observed at doses up to 0.6 mg/kg/day (5200-times the human systemic exposure to bimatoprost from DURYSTA, based on C max ). In a pre/postnatal development study, oral administration of bimatoprost to pregnant rats from gestation day 7 through lactation resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at 0.3 mg/kg/day (estimated 470-times the human systemic exposure to bimatoprost from DURYSTA, based plasma C max and a blood-to plasma partition ratio of 0.858). No adverse effects were observed in rat offspring at 0.1 mg/kg/day (estimated 350-times the human systemic exposure to bimatoprost from DURYSTA, based on plasma C max ). 8.2 Lactation Risk Summary There is no information regarding the presence of bimatoprost in human milk, the effects on the breastfed infants, or the effects on milk production. In animal studies, topical bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when DURYSTA is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered, along with the mother's clinical need for DURYSTA and any potential adverse effects on the breastfed child from DURYSTA. 8.4 Pediatric Use Safety and effectiveness of DURYSTA in pediatric patients have not been established. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of DURYSTA (bimatoprost intracameral implant) administration in pregnant women to inform a drug associated risk. Oral administration of bimatoprost to pregnant rats and mice throughout organogenesis did not produce adverse maternal or fetal effects at clinically relevant exposures. Oral administration of bimatoprost to rats from the start of organogenesis to the end of lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant exposures [see Animal Data] . Data Animal Data In an embryofetal development rat study, oral administration of bimatoprost to pregnant rats during organogenesis produced abortion at 0.6 mg/kg/day (1770-times the human systemic exposure to bimatoprost from DURYSTA, based on C max and a blood-to plasma partition ratio of 0.858). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 470-times the human systemic exposure to bimatoprost from DURYSTA, based on C max ). No fetal abnormalities were observed at doses up to 0.6 mg/kg/day. In an embryofetal development mouse study, oral administration of bimatoprost to pregnant mice during organogenesis produced abortion and early delivery at 0.3 mg/kg/day (2240-times the human systemic exposure to bimatoprost from DURYSTA, based on plasma C max level; blood-to plasma partition ratio of 0.858). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (400-times the human systemic exposure to bimatoprost from DURYSTA, based on C max ). No fetal abnormalities were observed at doses up to 0.6 mg/kg/day (5200-times the human systemic exposure to bimatoprost from DURYSTA, based on C max ). In a pre/postnatal development study, oral administration of bimatoprost to pregnant rats from gestation day 7 through lactation resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at 0.3 mg/kg/day (estimated 470-times the human systemic exposure to bimatoprost from DURYSTA, based plasma C max and a blood-to plasma partition ratio of 0.858). No adverse effects were observed in rat offspring at 0.1 mg/kg/day (estimated 350-times the human systemic exposure to bimatoprost from DURYSTA, based on plasma C max ).

11 DESCRIPTION DURYSTA is a sterile intracameral implant containing 10 mcg of bimatoprost, a prostaglandin analog, in a solid polymer sustained-release drug delivery system (DDS). The drug delivery system consists of poly (D,L-lactide), poly (D,L-lactide-co-glycolide), poly (D,L-lactide) acid end, and polyethylene glycol 3350. DURYSTA is preloaded into a single-use, DDS applicator to facilitate injection of the rod-shaped implant directly into the anterior chamber of the eye. The chemical name for bimatoprost is ( Z )-7-[(1 R ,2 R ,3 R ,5 S )-3,5-dihydroxy-2-[(1 E ,3 S )-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]- N -ethyl-5-heptenamide, and its molecular weight is 415.57. Its molecular formula is C 25 H 37 NO 4 . Its structural formula is: Bimatoprost is a white to off-white powder, soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. The polymer matrix slowly degrades to lactic acid and glycolic acid. The chemical name for bimatoprost is (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-N-ethyl-5-heptenamide, and its molecular weight is 415.57. Its molecular formula is C25H37NO4.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. Bimatoprost is believed to lower IOP in humans by increasing outflow of aqueous humor through both the trabecular meshwork (conventional) and uveoscleral routes (unconventional). Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. 12.3 Pharmacokinetics After a single administration of DURYSTA, bimatoprost concentrations were below the lower limit of quantitation (0.001 ng/mL) in the majority (approximately 92%) of patients. The maximum bimatoprost concentration observed in any patient was 0.00224 ng/mL. Bimatoprost acid concentrations were also below the lower limit of quantitation (0.01 ng/mL) in almost all (approximately 99%) of patients.

12.1 Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. Bimatoprost is believed to lower IOP in humans by increasing outflow of aqueous humor through both the trabecular meshwork (conventional) and uveoscleral routes (unconventional). Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

12.3 Pharmacokinetics After a single administration of DURYSTA, bimatoprost concentrations were below the lower limit of quantitation (0.001 ng/mL) in the majority (approximately 92%) of patients. The maximum bimatoprost concentration observed in any patient was 0.00224 ng/mL. Bimatoprost acid concentrations were also below the lower limit of quantitation (0.01 ng/mL) in almost all (approximately 99%) of patients.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses up to 2 mg/kg/day and 1 mg/kg/day respectively for 104 weeks (approximately 3100 and 1700 times, respectively, the maximum human exposure [based on plasma C max levels; blood-to-plasma partition ratio of 0.858]). Mutagenesis Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Impairment of Fertility Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (1770-times the maximum human exposure, based on plasma C max ; blood-to-plasma partition ratio of 0.858).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses up to 2 mg/kg/day and 1 mg/kg/day respectively for 104 weeks (approximately 3100 and 1700 times, respectively, the maximum human exposure [based on plasma C max levels; blood-to-plasma partition ratio of 0.858]). Mutagenesis Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Impairment of Fertility Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (1770-times the maximum human exposure, based on plasma C max ; blood-to-plasma partition ratio of 0.858).

14 CLINICAL STUDIES Efficacy was evaluated in two multicenter, randomized, parallel-group, controlled 20-month (including 8-month extended follow-up) studies of DURYSTA compared to twice daily topical timolol 0.5% drops, in patients with OAG or OHT. DURYSTA demonstrated an IOP reduction of approximately 5-8 mmHg in patients with a mean baseline IOP of 24.5 mmHg (see Figures 3 and 4). Figure 3: Study 1 Mean IOP (mmHg) by Treatment Group and Treatment Difference in Mean IOP Figure 4: Study 2 Mean IOP (mmHg) by Treatment Group and Treatment Difference in Mean IOP Figure 3 Figure 4

16 HOW SUPPLIED/STORAGE AND HANDLING DURYSTA contains a 10 mcg bimatoprost intracameral implant in a single-use applicator that is packaged in a sealed foil pouch containing desiccant, NDC 0023-9652-01. Storage Store refrigerated at 2°C to 8°C (36°F to 46°F).

17 PATIENT COUNSELING INFORMATION Treatment-related Effects Advise patients about the potential risk for complications including, but not limited to, the development of corneal adverse events, intraocular inflammation or endophthalmitis [ see Warnings and Precautions ( 5.1 , 5.4 , 5.6 )] . Potential for Pigmentation Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent [ see Warnings and Precautions ( 5.5 )] . When to Seek Physician Advice Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist [ see Warnings and Precautions ( 5.6 )] . Distributed by: AbbVie Inc. North Chicago, IL 60064 © 2024 AbbVie. All rights reserved. DURYSTA and its design are trademarks of Allergan, Inc., an AbbVie company. V2.0USPI9652 Abbvie Logo