DESCRIPTION Latanoprost is a prostaglandin F2a analogue. Its chemical name is isopropyl-(Z)-7[(5R,2R,3R,6S)3,5-dihydroxy-2-[(3R)- 3-hydroxybutyl-5-phenylpentyl]cyclopentyl]-5-heptenoate. Its molecular formula is C4026H40O5 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 latanoprost latanoprost latanoprost benzalkonium chloride sodium chloride sodium dihydrogen phosphate monohydrate disodium hydrogen phosphate anhydrous water for injection
CLINICAL PHARMACOLOGY
Mechanism of action Latanoprost is a prostanoid selective RT receptor agaonist that is believed to reduce the intraocular . .
Absorption Latanoprost is absorbed through the cornea where the isopropyl ester . .
Distribution The distribution volume in humans . .
Metabolism Latanprost, an isopropyl ester prodrug, is hydrolyzed by esterases . .
Excretion The elimination of the acid of latanoprost from human . .
Animal Studies In monkeys, latanoprost has been shown to induce . . Ocular administration of latanoprost at a dose of . .
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.
CLINICAL STUDIES Patients with mean baseline intraocular pressure of 24-25 mmHg . . A 3-year open-label, prospective safety study with 2-year extension . . Results showed that the onset of noticeable iris pigmentation . .
CONTRAINDICATIONS Known hypersensitivity to latanprost, benzalkonium chloride or any other ingredients in this product.
WARNINGS XALATAN Sterile Ophthalmic Solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been . .
General XALATAN Sterile Ophthalmic Solution may gradually decrease the pigmentation of the iris . . During clinical trials, the increase in brown iris pigment . . Eyelid skin darkening, which may be irreversible, . . XALATAN may gradually change eyelashes and vellus hair . . XALATAN should be used with caution in patients with . . Macular edema, including cystoid macular oedema, . . There is limited experience with XALATAN. . There have been reports of bacterial keratitis . . Contact lenses should be removed prior to the administration . .
Information for Patients Patients should be advised about the potential for increased brown . . Patients should also be informed of the possibility of eyelash . . Patients should be instructed to avoid allowing the tip . . Patients should also be advised that if they develop an intercurrent . . Patients should be advised that if they develop any ocular reactions . . Patients should also be advised that XALATAN contains . . If more than one topical ophthalmic drug is being used . .
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 Latanprost 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 . . Additional in vitro and in vivo studies on unscheduled DNA synthesis . .
Teratogenic Effects Pregnancy Category C. Reproduction studies have been performed in rats and rabbits. In rabbits an incidence . .
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.
ADVERSE REACTIONS
Adverse events referred to in other sections of this insert Eyelash changes (increased length, thickness, pigmentation . .
Controlled Clinical Trials: The ocular adverse events and ocular signs and symptoms reported in 5 to 15% of the patients . . Local conjunctival hyperemia was observed; however, less than 1% . . In addition to the above listed ocular events/signs and symptoms, the following were reported in 1 to 4% . . The following events were reported in less than 1% of patients: conjunctivitis, diplopia and discharge from the eye. During clinical studies, there were extremely rare reports . . The most common systemic adverse events seen . .
Clinical Practice The following events have been identified during postmarketing use . .
OVERDOSAGE Apart from ocular irritation and conjunctival or episcleral . . If overdosage with XALATAN Sterile Ophthalmic Solution occurs, treatment should be symptomatic.
DOSAGE AND ADMINISTRATION The recommended dosage is one drop (1.5 µg) in the affected eye(s) once daily in the evening. The dosage of XALATAN Sterile Ophthalmic Solution should not exceed once daily since it has been shown that more frequent administration may decrease the intraocular pressure lowering effect. 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 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.
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 polyethyelene overcap. NDC 0013-8303-04 2.5 mL fill, 0.005% (50 µg/mL). Storage: Protect from light. Store unopened bottle under refrigeration at 2ºto 8ºC (36ºto 46ºF). Once opened the 2.5 mL container may be stored at room temperature up to 25 ºC (77Fº) for 6 weeks. Xalatan