latanoprost 125 MCG per 2.5 ML Ophthalmic Solution

WARNINGS

XALATAN Sterile 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, and growth of eyelashes.

Pigmentation is expected to increase as long as XALATAN is administered.

After discontinuation of XALATAN, 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 effects of increased pigmentation beyond 5 years are not known.

DRUG INTERACTIONS

Drug Interactions 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.

OVERDOSAGE

Apart from ocular irritation and conjunctival or episcleral hyperemia, the ocular effects of latanoprost administered at high doses are not known.

Intravenous administration of large doses of latanoprost in monkeys has been associated with transient bronchoconstriction; however, in 11 patients with bronchial asthma treated with latanoprost, bronchoconstriction was not induced.

Intravenous infusion of up to 3 µg/kg in healthy volunteers produced mean plasma concentrations 200 times higher than during clinical treatment and no adverse reactions were observed.

Intravenous dosages of 5.5 to 10 µg/kg caused abdominal pain, dizziness, fatigue, hot flushes, nausea and sweating.

If overdosage with XALATAN Sterile Ophthalmic Solution occurs, treatment should be symptomatic.

DESCRIPTION

Latanoprost is a prostaglandin F 2α analogue.

Its chemical name is isopropyl-(Z)-7[(1R,2R,3R,5S)3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate.

Its molecular formula is C 26 H 40 O 5 and its chemical structure is: Latanoprost is a colorless to slightly yellow oil that is very soluble in acetonitrile and freely soluble in acetone, ethanol, ethyl acetate, isopropanol, methanol and octanol.

It is practically insoluble in water.

XALATAN Sterile Ophthalmic Solution (latanoprost ophthalmic solution) is supplied as a sterile, isotonic, buffered aqueous solution of latanoprost with a pH of approximately 6.7 and an osmolality of approximately 267 mOsmol/kg.

Each mL of XALATAN contains 50 micrograms of latanoprost.

Benzalkonium chloride, 0.02% is added as a preservative.

The inactive ingredients are: sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous and water for injection.

One drop contains approximately 1.5 µg of latanoprost.

Chemical Structure

CLINICAL STUDIES

Patients with mean baseline intraocular pressure of 24 – 25 mmHg who were treated for 6 months in multi-center, randomized, controlled trials demonstrated 6 –8 mmHg reductions in intraocular pressure.

This IOP reduction with XALATAN Sterile Ophthalmic Solution 0.005% dosed once daily was equivalent to the effect of timolol 0.5% dosed twice daily.

A 3-year open-label, prospective safety study with a 2-year extension phase was conducted to evaluate the progression of increased iris pigmentation with continuous use of XALATAN once-daily as adjunctive therapy in 519 patients with open-angle glaucoma.

The analysis was based on observed-cases population of the 380 patients who continued in the extension phase.

Results showed that the onset of noticeable increased iris pigmentation occurred within the first year of treatment for the majority of the patients who developed noticeable increased iris pigmentation.

Patients continued to show signs of increasing 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.

HOW SUPPLIED

XALATAN Sterile Ophthalmic Solution is a clear, isotonic, buffered, preserved colorless solution of latanoprost 0.005% (50 µg/mL).

It is supplied as a 2.5 mL solution in a 5 mL clear low density polyethylene bottle with a clear low density polyethylene dropper tip, a turquoise high density polyethylene screw cap, and a tamper-evident clear low density polyethylene overcap.

2.5 mL fill, 0.005% (50 µg/mL) Package of 1 bottle NDC 0013-8303-04 Storage 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.

GERIATRIC USE

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

MECHANISM OF ACTION

Mechanism of Action 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.

INDICATIONS AND USAGE

XALATAN Sterile Ophthalmic Solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

PEDIATRIC USE

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

PREGNANCY

Pregnancy Teratogenic Effects Pregnancy Category C Reproduction studies have been performed in rats and rabbits.

In rabbits an incidence of 4 of 16 dams had no viable fetuses at a dose that was approximately 80 times the maximum human dose, and the highest nonembryocidal dose in rabbits was approximately 15 times the maximum human dose.

There are no adequate and well-controlled studies in pregnant women.

XALATAN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

NUSRING MOTHERS

Nursing Mothers 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.

INFORMATION FOR PATIENTS

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.

DOSAGE AND ADMINISTRATION

The recommended dosage is one drop (1.5 µg) in the affected eye(s) once daily in the evening.

If one dose is missed, treatment should continue with the next dose as normal.

The dosage of XALATAN Sterile Ophthalmic Solution should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including XALATAN Sterile Ophthalmic Solution is not recommended.

It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure lowering effect or cause paradoxical elevations in IOP.

Reduction of the intraocular pressure starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours.

XALATAN may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure.

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