Label: XALATAN- latanoprost solution

  • NDC Code(s): 0013-8303-01
  • Packager: Pharmacia and Upjohn Company LLC
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: New Drug Application

Drug Label Information

Updated April 9, 2019

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use XALATAN safely and effectively. See full prescribing information for XALATAN.

    XALATAN ® (latanoprost ophthalmic solution) 0.005%
    Initial U.S. Approval: 1996

    INDICATIONS AND USAGE

    XALATAN is a prostaglandin F analogue indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. (1)

    DOSAGE AND ADMINISTRATION

    One drop in the affected eye(s) once daily in the evening. (2)

    DOSAGE FORMS AND STRENGTHS

    Ophthalmic solution containing 50 mcg/mL latanoprost (0.005%). (3)

    CONTRAINDICATIONS

    Known hypersensitivity to latanoprost, benzalkonium chloride, or any other ingredients in this product. (4)

    WARNINGS AND PRECAUTIONS

    • Pigmentation: pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation likely to be permanent. (5.1)
    • Eyelash Changes: gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible. (5.2)

    ADVERSE REACTIONS

    Most common adverse reactions (≥4%) from clinical trials are blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, punctate epithelial keratopathy, and upper respiratory tract infection/cold/flu. (6)


    To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    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 5 minutes apart. (7)

    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 4/2013

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  • FULL PRESCRIBING INFORMATION: CONTENTS*
  • 1 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.

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  • 2 DOSAGE AND ADMINISTRATION

    The recommended dosage is one drop 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 should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including XALATAN is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure (IOP) lowering effect or cause paradoxical elevations in IOP.

    Reduction of the IOP 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 IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Contact lenses should be removed prior to the administration of XALATAN, and may be reinserted 15 minutes after administration

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  • 3 DOSAGE FORMS AND STRENGTHS

    Sterile ophthalmic solution containing 50 mcg/mL latanoprost.

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  • 4 CONTRAINDICATIONS

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

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  • 5 WARNINGS AND PRECAUTIONS

    5.1 Pigmentation

    XALATAN 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. Where pigmentation occurs it may 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. Beyond 5 years the effects of increased pigmentation are not known (see section 14.2).

    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 XALATAN can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information (17.1)].

    5.2 Eyelash Changes

    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 [see Patient Counseling Information (17.2)].

    5.3 Intraocular Inflammation

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

    5.4 Macular Edema

    Macular edema, including cystoid macular edema, has been reported during treatment with XALATAN. XALATAN 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 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 [see Patient Counseling Information (17.3)].

    5.6 Use with Contact Lenses

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

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  • 6 ADVERSE REACTIONS

    The following adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the label:

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

    XALATAN was studied in three multicenter, randomized, controlled clinical trials. Patients received 50 mcg/mL XALATAN once daily or 5 mg/mL active-comparator (timolol) twice daily. The patient population studied had a mean age of 65±10 years. Seven percent of patients withdrew before the 6-month endpoint.

    Table 1: Ocular Adverse Reactions and ocular signs/symptoms reported by 5–15% of patients receiving Latanoprost
    Symptom/Finding Adverse Reactions (incidence (%))
    Latanoprost
    (n=460)
    Timolol
    (n=369)
    Foreign body sensation 13.3 8.4
    Punctate epithelial keratopathy 9.6 8.7
    Stinging 9.3 12.2
    Conjunctival hyperemia 8.0 3.3
    Blurred vision 7.6 8.1
    Itching 7.6 8.1
    Burning 7.4 7.6
    Increased pigmentation of the iris 7.2 0

    Less than 1% of the patients treated with XALATAN required discontinuation of therapy because of intolerance to conjunctival hyperemia.

    Table 2: Adverse Reactions that were reported in 1–5% of patients receiving latanoprost
    Adverse Reactions (incidence (%))
    Latanoprost
    (n=460)
    Timolol
    (n=369)
    Ocular Events/Signs and Symptoms
      Excessive tearing 4.1 6.0
      Lid discomfort/pain 3.7 2.2
      Dry eye 3.3 2.7
      Eye pain 3.0 3.3
      Lid crusting 3.0 3.3
      Lid erythema 3.0 2.2
      Photophobia 1.7 1.4
      Lid edema 1.5 3.3
    Systemic Events
      Upper respiratory tract infection/cold/flu 3.5 3.0
      Muscle/joint/back pain 1.5 0.5
      Rash/allergic skin reaction 1.1 0.3
      Chest pain/angina pectoris 0.7 0

    The following reactions were reported in less than 1% of the latanoprost patients: conjunctivitis (0.9%), diplopia (0.7%), and discharge from the eye (0.2%).

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

    6.2 Postmarketing Experience

    The following reactions 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 reactions, 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:

    Nervous System disorders: dizziness, headache, and toxic epidermal necrolysis

    Eye Disorders: eyelash and vellus hair changes (increased length, thickness, pigmentation, and number); keratitis; corneal edema and erosions; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema; misdirected eyelashes sometimes resulting in eye irritation; periorbital and lid changes resulting in deepening of the eyelid sulcus

    Respiratory, Thoracic and Mediastinal Disorders: asthma and exacerbation of asthma; dyspnea

    Skin and Subcutaneous Tissue Disorders: eyelid skin darkening

    Infections and Infestations: Herpes keratitis

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  • 7 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.

    The combined use of two or more prostaglandins, or prostaglandin analogs including XALATAN is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the IOP lowering effect or cause paradoxical elevations in IOP.

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  • 8 USE IN SPECIFIC POPULATIONS

    8.1 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.

    8.3 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.

    8.4 Pediatric Use

    Safety and effectiveness in pediatric patients have not been established.

    8.5 Geriatric Use

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

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  • 10 OVERDOSAGE

    Intravenous infusion of up to 3 mcg/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 mcg/kg caused abdominal pain, dizziness, fatigue, hot flushes, nausea, and sweating.

    If overdosage with XALATAN occurs, treatment should be symptomatic.

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  • 11 DESCRIPTION

    Latanoprost is a prostaglandin F2α 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 C26H40O5 and its chemical structure is:

    Chemical Structure

    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 (latanoprost ophthalmic solution) 0.005% 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 mcg of latanoprost.

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  • 12 CLINICAL PHARMACOLOGY

    12.1 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.

    12.2 Pharmacodynamics

    Reduction of the IOP in man starts about 3–4 hours after administration and maximum effect is reached after 8–12 hours. IOP reduction is present for at least 24 hours.

    12.3 Pharmacokinetics

    Absorption

    Latanoprost is absorbed through the cornea where the isopropyl ester prodrug is hydrolyzed to the acid form to become biologically active.

    Distribution

    The distribution volume in humans is 0.16 ± 0.02 L/kg. The acid of latanoprost can be measured in aqueous humor during the first 4 hours, and in plasma only during the first hour after local administration. Studies in man indicate that the peak concentration in the aqueous humor is reached about two hours after topical administration.

    Metabolism

    Latanoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to the biologically active acid. The active acid of latanoprost reaching the systemic circulation is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation.

    Excretion

    The elimination of the acid of latanoprost from human plasma is rapid (t1/2 = 17 min) after both intravenous and topical administration. Systemic clearance is approximately 7 mL/min/kg. Following hepatic β-oxidation, the metabolites are mainly eliminated via the kidneys. Approximately 88% and 98% of the administered dose are recovered in the urine after topical and intravenous dosing, respectively.

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  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Latanoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 170 mcg/kg/day (approximately 2800 times the recommended maximum human dose) for up to 20 and 24 months, respectively.

    Latanoprost was not mutagenic in bacteria, in mouse lymphoma, or in mouse micronucleus tests. Chromosome aberrations were observed in vitro with human lymphocytes. 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.

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  • 14 CLINICAL STUDIES

    14.1 Elevated Baseline IOP

    Patients with mean baseline IOP of 24 – 25 mmHg who were treated for 6 months in multi-center, randomized, controlled trials demonstrated 6 – 8 mmHg reductions in IOP. This IOP reduction with XALATAN 0.005% dosed once daily was equivalent to the effect of timolol 0.5% dosed twice daily.

    14.2 Progression of Increased Iris Pigmentation

    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.

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  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    XALATAN is a clear, isotonic, buffered, preserved colorless solution of latanoprost 0.005% (50 mcg/mL). It is supplied as a 2.5 mL solution in a 5 mL clear low density polyethylene bottle with a clear 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 mcg/mL): Package of 1 bottle: NDC 0013-8303-04
    2.5 mL fill, 0.005% (50 mcg/mL): Multi-pack of 3 bottles: NDC 0013-8303-01

    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.

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  • 17 PATIENT COUNSELING INFORMATION

    17.1 Potential for Pigmentation

    Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent. Inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of XALATAN [see Warnings and Precautions (5.1)].

    17.2 Potential for Eyelash Changes

    Inform patients 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.

    17.3 Handling the Container

    Instruct patients 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 [see Warnings and Precautions (5.5)].

    17.4 When to Seek Physician Advice

    Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection) or have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice concerning the continued use of the multiple-dose container.

    17.5 Use with Contact Lenses

    Advise patients 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.

    17.6 Use with Other Ophthalmic Drugs

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

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  • SPL UNCLASSIFIED SECTION

    Logo

    Pfizer Manufacturing Belgium NV
    Puurs, Belgium

    LAB-0135-10.2

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  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL - 2.5 mL Vial Label

    Xalatan®

    latanoprost
    ophthalmic solution

    Sterile
    0.005%

    125 µg/2.5 mL

    8Q2412

    PRINCIPAL DISPLAY PANEL - 2.5 mL Vial Label
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  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL - 2.5 mL Bottle Carton

    NDC 0013-8303-04

    Pfizer

    Xalatan®
    latanoprost ophthalmic solution

    STERILE
    0.005%

    125 µg/2.5 mL*

    One 2.5 mL Bottle
    Rx only

    PRINCIPAL DISPLAY PANEL - 2.5 mL Bottle Carton
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  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL - Multi-Pack Bottle Carton

    Pfizer

    NDC 0013-8303-01

    Xalatan®
    latanoprost ophthalmic solution

    STERILE
    0.005%

    125 µg/2.5 mL*

    Multi-Pack
    Three 2.5 mL bottles
    Not to be sold separately.

    Rx only

    PRINCIPAL DISPLAY PANEL - Multi-Pack Bottle Carton
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  • INGREDIENTS AND APPEARANCE
    XALATAN 
    latanoprost solution
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0013-8303
    Route of Administration OPHTHALMIC
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    LATANOPROST (UNII: 6Z5B6HVF6O) (LATANOPROST - UNII:6Z5B6HVF6O) LATANOPROST 50 ug  in 1 mL
    Inactive Ingredients
    Ingredient Name Strength
    BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)  
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    SODIUM PHOSPHATE, DIBASIC, ANHYDROUS (UNII: 22ADO53M6F)  
    WATER (UNII: 059QF0KO0R)  
    SODIUM PHOSPHATE, MONOBASIC, UNSPECIFIED FORM (UNII: 3980JIH2SW)  
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:0013-8303-01 3 in 1 PACKAGE 03/20/1995 03/31/2015
    1 2.5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA020597 03/20/1995
    Labeler - Pharmacia and Upjohn Company LLC (618054084)
    Establishment
    Name Address ID/FEI Business Operations
    Chinoin Pharmaceutical and Chemical Works Private 643939754 API MANUFACTURE(0013-8303)
    Establishment
    Name Address ID/FEI Business Operations
    Catalent Pharma Solutions, LLC 043911403 MANUFACTURE(0013-8303)
    Establishment
    Name Address ID/FEI Business Operations
    Pfizer Pharmaceuticals LLC 829084545 API MANUFACTURE(0013-8303)
    Establishment
    Name Address ID/FEI Business Operations
    Pfizer Manufacturing Belgium NV 370156507 ANALYSIS(0013-8303) , MANUFACTURE(0013-8303)
    Establishment
    Name Address ID/FEI Business Operations
    Pharmacia and Upjohn Company LLC 618054084 MANUFACTURE(0013-8303) , PACK(0013-8303)
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