5 WARNINGS AND PRECAUTIONS

5.1 Pigmentation

Topical latanoprost ophthalmic products, including XELPROS, have 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. 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 XELPROS can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

5.2 Eyelash Changes

Latanoprost ophthalmic products, including XELPROS, 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.

5.3 Intraocular Inflammation

XELPROS 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 ophthalmic products, including XELPROS. XELPROS 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. XELPROS should be used with caution in patients with a history of herpetic keratitis. XELPROS 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.

5.7 Contact Lens Use

Contact lenses should be removed prior to the administration of XELPROS and may be reinserted 15 minutes after administration.