Travoprost

5 WARNINGS AND PRECAUTIONS Pigmentation: Pigmentation of the iris, periorbital tissue (eyelid), and eyelashes can occur. Iris pigmentation 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 Travoprost 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 travoprost 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 travoprost, 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 travoprost ophthalmic solution can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly . 5.2 Eyelash Changes Travoprost ophthalmic solution 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 Travoprost ophthalmic solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. 5.4 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with travoprost ophthalmic solution. Travoprost 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 Angle-closure, Inflammatory or Neovascular Glaucoma Travoprost ophthalmic solution has not been evaluated for the treatment of angle-closure, inflammatory or neovascular glaucoma. 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. 5.7 Use with Contact Lenses Contact lenses should be removed prior to instillation of travoprost ophthalmic solution and may be reinserted 15 minutes following its administration.

6 ADVERSE REACTIONS Most common adverse reaction (30% to 50%) is conjunctival hyperemia (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1-800-417-9175 or the 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 adverse reaction observed in controlled clinical trials with travoprost ophthalmic solution 0.004% was ocular hyperemia, which was reported in 30% to 50% of patients. Up to 3% of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions, reported at an incidence of 5% to 10% in these clinical trials, included decreased visual acuity, eye discomfort, foreign body sensation, pain, and pruritus. Ocular adverse reactions, reported at an incidence of 1% to 4% in clinical trials with travoprost ophthalmic solution 0.004%, included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival hemorrhage, and tearing. Non-ocular adverse reactions, reported at an incidence of 1% to 5% in these clinical studies, were allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence, and urinary tract infections. 6.2 Postmarketing Experience Additional adverse reactions have been identified during post approval use of travoprost ophthalmic solution 0.004% 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 travoprost ophthalmic solution, or a combination of these factors, include: arrhythmia, vomiting, epistaxis, tachycardia, and insomnia. In postmarketing use with prostaglandin analogs, periorbital and lid changes, including deepening of the eyelid sulcus have been observed.