d of the possibility of increased pigmentation. beyond 5 years the effects of increased pigmentation are not known [ see clinical studies (14.2 )]. 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 latanoprost can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [ see patient counseling information (17.1) ]. 5.2 eyelash changes latanoprost 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 (17.2) ]. 5.3 intraocular inflammation latanoprost 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 inflammation may be exacerbated. 5.4 macular edema macular edema, including cystoid macular edema, has been reported during treatment with latanoprost. latanoprost ophthalmic solution 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 herpetic keratitis reactivation of herpes simplex keratitis has been reported during treatment with latanoprost ophthalmic solution. latanoprost should be used with caution in patients with a history of herpetic keratitis. latanoprost should be avoided in cases of active herpes simplex keratitis because inflammation may be exacerbated. 5.6 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 (17.3) ]. 5.7 use with contact lenses contact lenses should be removed prior to the administration of latanoprost ophthalmic solution, and may be reinserted 15 minutes after administration.

stration of latanoprost ophthalmic solution, and may be reinserted 15 minutes after administration. one drop in the affected eye(s) once daily in the evening. ( 2 )

h america llc at 1-800-321-4576 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, the adverse reaction rates observed in the clinical studies 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. latanoprost was studied in three multicenter, randomized, controlled clinical trials. patients received 50 mcg/ml latanoprost once daily or 5 mg/ml active-comparator (timolol) twice daily. the patient population studied had a mean age of 65 + 10 years. seven percent of patients withdrew before the 6-month endpoint. table 1: ocular adverse reactions and ocular signs/symptoms reported by 5–15% of patients receiving latanoprost symptom/finding adverse reactions (incidence (%)) latanoprost (n=460) timolol (n=369) foreign body sensation 13 8 punctate epithelial keratopathy 10 9 stinging 9 12 conjunctival hyperemia 8 3 blurred vision 8 8 itching 8 8 burning 7 8 increased pigmentation of the iris 7 0 less than 1% of the patients treated with latanoprost required discontinuation of therapy because of intolerance to conjunctival hyperemia. table 2: adverse reactions that were reported in 1–5% of patients receiving latanoprost adverse reactions (incidence (%)) latanoprost (n=460) timolol (n=369) ocular events/signs and symptoms excessive tearing 4 6 lid discomfort/pain 4 2 dry eye 3 3 eye pain 3 3 lid crusting 3 3 lid erythema 3 2 photophobia 2 1 lid edema 1 3 systemic events upper respiratory tract infection/cold/flu 3 3 muscle/joint/back pain 1 0.5 rash/allergic skin reaction 1 0.3 6.2 postmarketing experience the following reactions have been identified during postmarketing use of latanoprost in clinical practice. because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. the reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to latanoprost, or a combination of these factors, include: nervous system disorders: dizziness, headache, and toxic epidermal necrolysis eye disorders: eyelash and vellus hair changes (increased length, thickness, pigmentation, and number); keratitis; corneal edema and erosions; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema; misdirected eyelashes sometimes resulting in eye irritation; periorbital and lid changes resulting in deepening of the eyelid sulcus. respiratory, thoracic and mediastinal disorders: asthma and exacerbation of asthma; dyspnea skin and subcutaneous tissue disorders: eyelid skin darkening infections and infestations: herpes keratitis

tients.

and in plasma only during the first hour after local administration. studies in man indicate that the peak concentration in the aqueous humor is reached about two hours after topical administration. metabolism latanoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to the biologically active acid. the active acid of latanoprost reaching the systemic circulation is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation. excretion the elimination of the acid of latanoprost from human plasma is rapid (t 1/2 = 17 min) after both intravenous and topical administration. systemic clearance is approximately 7 ml/min/kg. following hepatic β-oxidation, the metabolites are mainly eliminated via the kidneys. approximately 88% and 98% of the administered dose are recovered in the urine after topical and intravenous dosing, respectively.

s approximately 7 ml/min/kg. following hepatic β-oxidation, the metabolites are mainly eliminated via the kidneys. approximately 88% and 98% of the administered dose are recovered in the urine after topical and intravenous dosing, respectively.

g iris pigmentation throughout the five years of the study. observation of increased iris pigmentation did not affect the incidence, nature, or severity of adverse events (other than increased iris pigmentation) recorded in the study. iop reduction was similar regardless of the development of increased iris pigmentation during the study.

cause ocular infections. serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [ see warnings and precautions (5.6) ]. 17.4 when to seek physician advice advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection) or 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 the multiple-dose container. 17.5 use with contact lenses advise patients that latanoprost ophthalmic solution contains benzalkonium chloride, which may be absorbed by contact lenses. contact lenses should be removed prior to administration of the solution. lenses may be reinserted 15 minutes following administration of latanoprost ophthalmic solution. 17.6 use with other ophthalmic drugs if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. bausch + lomb, a division of valeant pharmaceuticals north america llc bridgewater, nj 08807 usa ©bausch & lomb incorporated relabeled by: proficient rx, lp thousand oaks, ca 91320 revised: june 2016 9144707 (flat) 9144807 (folded)