Xalatan Description

Latanoprost is a prostaglandin F2? 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 C26 H40 O5 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.

Xalatan 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.

Xalatan Contraindications

Known hypersensitivity to latanoprost, benzalkonium chloride or any other ingredients in this product.

Xalatan Side Effects

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.

Xalatan Precautions

General

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 ).

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.

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.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

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.

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.

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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

Xalatan 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.

Xalatan 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.