Xalatan ® latanoprost ophthalmic solution 0.005% (50 µg/mL)

Latanoprost is a prostanoid selective FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies in animals and man suggest that the main mechanism of action is increased uveoscleral outflow. Elevated IOP represents 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.

In monkeys, latanoprost has been shown to induce increased pigmentation of the iris. The mechanism of increased pigmentation seems to be stimulation of melanin production in melanocytes of the iris, with no proliferative changes observed. The change in iris color may be permanent.

Ocular administration of latanoprost at a dose of 6 µg/eye/day (4 times the daily human dose) to cynomolgus monkeys has also been shown to induce increased palpebral fissure. This effect was reversible upon discontinuation of the drug.

XALATAN Sterile Ophthalmic Solution may gradually increase the pigmentation of the iris. The eye color change is due to increased melanin content in the stromal melanocytes of the iris rather than to an increase in the number of melanocytes. This change may not be noticeable for several months to years (see WARNINGS). 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 XALATAN can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

During clinical trials, the increase in brown iris pigment has not been shown to progress further upon discontinuation of treatment, but the resultant color change may be permanent.

Eyelid skin darkening, which may be reversible, has been reported in association with the use of XALATAN (see WARNINGS).

XALATAN 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.

XALATAN 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.

Macular edema, including cystoid macular edema, has been reported during treatment with XALATAN. These reports have mainly occurred in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. XALATAN should be used with caution in patients who do not have an intact posterior capsule or who have known risk factors for macular edema.

There is limited experience with XALATAN in the treatment of angle closure, inflammatory or neovascular glaucoma.

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 PRECAUTIONS, Information for Patients).

Contact lenses should be removed prior to the administration of XALATAN, and may be reinserted 15 minutes after administration (see PRECAUTIONS, Information for Patients).

(see WARNINGS and PRECAUTIONS)

Patients should be advised about the potential for increased brown pigmentation of the iris, which may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of XALATAN.

Patients should also be informed of the possibility of eyelash and vellus hair changes in the treated eye during treatment with XALATAN. 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.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Patients also should be advised that if they develop an intercurrent ocular condition (e.g., trauma, or infection) or have ocular surgery, they should immediately seek their physician's advice concerning the continued use of the multiple-dose container.

Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and lid reactions, they should immediately seek their physician's advice.

Patients should also be advised that XALATAN 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 XALATAN.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with XALATAN. If such drugs are used they should be administered at least five (5) minutes apart.

Latanoprost was not mutagenic in bacteria, in mouse lymphoma or in mouse micronucleus tests.

Chromosome aberrations were observed in vitro with human lymphocytes.

Latanoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 170 µg/kg/day (approximately 2,800 times the recommended maximum human dose) for up to 20 and 24 months, respectively.

Additional in vitro and in vivo studies on unscheduled DNA synthesis in rats were negative. Latanoprost has not been found to have any effect on male or female fertility in animal studies.

It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when XALATAN is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Eyelash changes (increased length, thickness, pigmentation, and number of lashes); eyelid skin darkening; intraocular inflammation (iritis/uveitis); iris pigmentation changes; and macular edema, including cystoid macular edema (see WARNINGS and PRECAUTIONS).

The ocular adverse events and ocular signs and symptoms reported in 5 to 15% of the patients on XALATAN Sterile Ophthalmic Solution in the three 6-month, multi-center, double-masked, active-controlled trials were blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, and punctate epithelial keratopathy.

Local conjunctival hyperemia was observed; however, less than 1% of the patients treated with XALATAN required discontinuation of therapy because of intolerance to conjunctival hyperemia.

In addition to the above listed ocular events/signs and symptoms, the following were reported in 1 to 4% of the patients: dry eye, excessive tearing, eye pain, lid crusting, lid discomfort/pain, lid edema, lid erythema, and photophobia.

The following events were reported in less than 1% of the patients: conjunctivitis, diplopia and discharge from the eye.

During clinical studies, there were extremely rare reports of the following: retinal artery embolus, retinal detachment, and vitreous hemorrhage from diabetic retinopathy.

The most common systemic adverse events seen with XALATAN were upper respiratory tract infection/cold/flu, which occurred at a rate of approximately 4%. Chest pain/angina pectoris, muscle/joint/back pain, and rash/allergic skin reaction each occurred at a rate of 1 to 2%.

The following events have been identified during postmarketing use of XALATAN in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to XALATAN, or a combination of these factors, include: asthma and exacerbation of asthma; corneal edema and erosions; dyspnea; eyelash and vellus hair changes (increased length, thickness, pigmentation, and number); eyelid skin darkening; herpes keratitis; intraocular inflammation (iritis/uveitis); keratitis; macular edema, including cystoid macular edema; misdirected eyelashes sometimes resulting in eye irritation; dizziness, headache, and toxic epidermal necrolysis.

Protect from light. Store unopened bottle(s) under refrigeration at 2° to 8°C (36° to 46°F). During shipment to the patient, the bottle may be maintained at temperatures up to 40°C (104°F) for a period not exceeding 8 days. Once a bottle is opened for use, it may be stored at room temperature up to 25°C (77°F) for 6 weeks.