Rocklatan

5. WARNINGS AND PRECAUTIONS • Pigmentation : Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation likely to be permanent. ( 5.2 ) • Eyelash Changes : Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible. ( 5.3 ) 5.1 Epithelial Corneal Edema ROCKLATAN contains netarsudil which has been associated with Epithelial corneal edema, described as honeycomb or bullous, and has been reported in some patients with pre-existing corneal stromal edema or following ocular procedures that could affect corneal endothelial function. Epithelial corneal edemal typically resolves upon discontinuation of ROCKLATAN. Advise patients to notify their physician if they experience eye pain or decreased vision while using ROCKLATAN [see Adverse Reactions ( 6.2 ) and Patient Counselling Information ( 17 )] . 5.2 Pigmentation ROCKLATAN contains latanoprost which 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 latanoprost 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 latanoprost, 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. Beyond 5 years the 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 ROCKLATAN can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information ( 17 ) ]. 5.3 Eyelash Changes ROCKLATAN contains latanoprost which may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible upon discontinuation of treatment [see Patient Counseling Information ( 17 ) ]. 5.4 Intraocular Inflammation ROCKLATAN contains latanoprost which should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation because it may exacerbate inflammation. 5.5 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with latanoprost. ROCKLATAN 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. 5.6 Herpetic Keratitis Reactivation of Herpes Simplex keratitis has been reported during treatment with latanoprost. ROCKLATAN should be used with caution in patients with a history of herpetic keratitis. ROCKLATAN should be avoided in cases of active herpes simplex keratitis because it may exacerbate inflammation. 5.7 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 [see Patient Counseling Information ( 17 )]. 5.8 Use with Contact Lenses Contact lenses should be removed prior to the administration of ROCKLATAN and may be reinserted 15 minutes after administration.

6. ADVERSE REACTIONS The most common adverse reaction is conjunctival hyperemia (59%). Other common adverse reactions were: instillation site pain (20%), corneal verticillata (15%), and conjunctival hemorrhage (11%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1 800 757 9195, 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 clinical practice. The most common ocular adverse reaction observed in controlled clinical studies with ROCKLATAN was conjunctival hyperemia which was reported in 59% of patients. Five percent of patients discontinued therapy due to conjunctival hyperemia. Other common ocular adverse reactions reported were: instillation site pain (20%), corneal verticillata (15%), and conjunctival hemorrhage (11%). Eye pruritus, visual acuity reduced, increased lacrimation, instillation site discomfort, and blurred vision were reported in 5-8% of patients. Other adverse reactions from clinical trials that have been reported with the individual components and not listed above include: Netarsudil 0.02% Instillation site erythema, corneal staining, increased lacrimation, and erythema of eyelid. Latanoprost 0.005% Foreign body sensation, punctate keratitis, burning and stinging, itching, increased pigmentation of the iris, excessive tearing, eyelid discomfort, dry eye, eye pain, eyelid margin crusting, erythema of the eyelid, upper respiratory tract infection/nasopharyngitis/influenza, photophobia, eyelid edema, myalgia/arthralgia/back pain, and rash/allergic reactions. 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of ROCKLATAN. 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. Netarsudil 0.02% Eye disorders: Epithelial corneal edema has been reported in some patients with pre-existing corneal stromal edema or ocular procedures that could affect corneal endothelial function. [see Warnings and Precautions ( 5.1 )] .