Label: GATIFLOXACIN- gatifloxacin solution/ drops

  • NDC Code(s): 68180-435-01
  • Packager: Lupin Pharmaceuticals, Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated December 1, 2016

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use Gatifloxacin Ophthalmic Solution, 0.5% safely and effectively. See full prescribing information for Gatifloxacin Ophthalmic Solution, 0.5%.

    Gatifloxacin Ophthalmic Solution, 0.5% for topical ophthalmic use
    Initial U.S. Approval: 1999

    RECENT MAJOR CHANGES

    Contraindications, Hypersensitivity (4)                                             09/2016

    Warnings and Precautions, Hypersensitivity (5.1)                           09/2016

    INDICATIONS AND USAGE

    Gatifloxacin ophthalmic solution, 0.5% is a quinolone antimicrobial indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Haemophilus influenzae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis group, Streptococcus oralis, Streptococcus pneumoniae (1)

    DOSAGE AND ADMINISTRATION

    Day 1: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times on Day 1.

    Days 2 through 7: Instill one drop two to four times daily in the affected eye(s) while awake on Days 2 through 7. (2)

    DOSAGE FORMS AND STRENGTHS

    Ophthalmic solution: 0.5% gatifloxacin (5 mg/mL) (3)

    CONTRAINDICATIONS

    Gatifloxacin ophthalmic solution, 0.5% is contraindicated in patients with a history of hypersensitivity to gatifloxacin, to other quinolones, or to any of the components in this medication. (4)

    WARNINGS AND PRECAUTIONS

    • Hypersensitivity (5.1)
    • Growth of Resistant Organisms with Prolonged Use (5.2)
    • Corneal Endothelial Cell Injury (5.3)

    ADVERSE REACTIONS

    Most common adverse reactions occurring in ≥ 1 % of patients included worsening of conjunctivitis, eye irritation, dysgeusia, and eye pain. (6)

    To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 12/2016

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  • FULL PRESCRIBING INFORMATION: CONTENTS*
  • 1 INDICATIONS AND USAGE

    Gatifloxacin ophthalmic solution, 0.5% is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

    • Aerobic gram-positive bacteria:

    Staphylococcus aureus

    Staphylococcus epidermidis

    Streptococcus mitis group* 

    Streptococcus oralis*

    Streptococcus pneumoniae

    • Aerobic gram-negative bacteria:

    Haemophilus influenzae

    *Efficacy for these organisms were studied in fewer than 10 infections.

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  • 2 DOSAGE AND ADMINISTRATION

    • Day 1: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times.
    • Day 2 through Day 7: Instill one drop two to four times daily in the affected eye(s) while awake.
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  • 3 DOSAGE FORMS AND STRENGTHS

    Ophthalmic solution: 0.5% gatifloxacin (5 mg/mL)

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  • 4 CONTRAINDICATIONS

    Gatifloxacin ophthalmic solution, 0.5% is contraindicated in patients with a history of hypersensitivity to gatifloxacin, to other quinolones, or to any of the components in this medication [see WARNINGS AND PRECAUTIONS (5.1)].

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  • 5 WARNINGS AND PRECAUTIONS

    5.1 Hypersensitivity

    Some patients receiving topical ophthalmic gatifloxacin experienced hypersensitivity reactions including anaphylactic reactions, angioedema (including pharyngeal, laryngeal, or facial edema), dyspnea, urticaria, and itching, even following a single dose. Rare cases of Stevens-Johnson Syndrome were reported in association with topical ophthalmic gatifloxacin use. If an allergic reaction to gatifloxacin occurs, discontinue the drug [see PATIENT COUNSELING INFORMATION (17)].

    5.2 Growth of Resistant Organisms with Prolonged Use

    Prolonged use of gatifloxacin ophthalmic solution, 0.5% may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, examine the patient with the aid of magnification, such as slit lamp biomicroscopy and where appropriate, fluorescein staining.

    5.3 Corneal Endothelial Cell Injury

    Gatifloxacin ophthalmic solution, 0.5% is for topical ophthalmic use. Gatifloxacin ophthalmic solution, 0.5% may cause corneal endothelial cell injury if introduced directly into the anterior chamber of the eye.

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  • 6 ADVERSE REACTIONS

    The following serious adverse reactions are described elsewhere in the labeling:

    • Hypersensitivity [see CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.1)]
    • Growth of Resistant Organisms With Prolonged Use [see WARNINGS AND PRECAUTIONS (5.2)]
    • Corneal Endothelial Cell Injury [see WARNINGS AND PRECAUTIONS (5.3)]

    6.1 Clinical Studies Experience

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

    In clinical studies of patients with bacterial conjunctivitis treated with gatifloxacin ophthalmic solution, 0.5% (N=717), the most frequently reported adverse reactions occurring in ≥ 1 % of patients were: worsening of the conjunctivitis, eye irritation, dysgeusia, and eye pain.

    Additional adverse reactions reported with other formulations of gatifloxacin ophthalmic solution in other clinical studies included chemosis, conjunctival hemorrhage, dry eye, eye discharge, eyelid edema, headache, increased lacrimation, keratitis, red eye, papillary conjunctivitis, and reduced visual acuity.

    6.2 Postmarketing Experience

    The following adverse reactions have been identified during post-approval use of gatifloxacin ophthalmic solution, 0.5% or with other formulations of gatifloxacin ophthalmic solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions included anaphylactic reactions and angioedema (including pharyngeal, oral or facial edema), blepharitis, dyspnea, eye pruritus, eye swelling (including corneal and conjunctival edema), hypersensitivity, including signs and symptoms of eye allergy and allergic dermatitis, nausea, pruritus (including pruritus generalized, rash, urticaria), and vision blurred.

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  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    There are no available data on the use of gatifloxacin ophthalmic solution, 0.5% in pregnant women to inform a drug-associated risk. Administration of oral gatifloxacin to pregnant rats and rabbits throughout organogenesis did not produce adverse development outcomes at clinically relevant doses. Administration of gatifloxacin to rats during late gestation through lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant doses.

    Data

    Animal Data:

    Oral administration of gatifloxacin to pregnant rats throughout organogenesis produced teratogenic effects in rat fetuses, including skeletal/craniofacial malformations, delayed ossification, atrial enlargement, and reduced fetal weight, at doses greater than or equal to 150 mg/kg/day (approximately 600-fold higher than the maximum recommended human ophthalmic dose [MRHOD] for gatifloxacin ophthalmic solution, 0.5% of 0.04 mg/kg/day, on a mg/m2 basis). No teratogenic effects were observed in rat or rabbit fetuses at doses of gatifloxacin up to 50 mg/kg/day (approximately 200- and 400-fold higher than the MRHOD, respectively, on a mg/m2 basis).

    In a perinatal/postnatal study in rats, oral administration of gatifloxacin during late gestation through lactation produced an increase in late gestation fetal loss and neonatal/perinatal mortality at 200 mg/kg/day (approximately 800-fold higher than the MRHOD on a mg/m2 basis).

    8.2 Lactation

    Risk Summary

    There is no information regarding the presence of gatifloxacin ophthalmic solution, 0.5% in human milk, the effect of gatifloxacin on breastfed infants, or the effect of gatifloxacin on milk production. Gatifloxacin was found in the breast milk of rats following oral administration of gatifloxacin during lactation. However, systemic levels of gatifloxacin following topical ocular administration are low [see CLINICAL PHARMACOLOGY (12.3)], and it is not known whether gatifloxacin would be present in maternal milk at measurable levels following topical ocular administration. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for gatifloxacin ophthalmic solution, 0.5% and any potential adverse effects on the breastfed child from gatifloxacin ophthalmic solution, 0.5%.

    8.4 Pediatric Use

    The safety and effectiveness of gatifloxacin ophthalmic solution, 0.5% in infants below one year of age have not been established. Gatifloxacin ophthalmic solution, 0.5% has been demonstrated in clinical trials to be safe and effective for the treatment of bacterial conjunctivitis in pediatric patients one year or older [see CLINICAL STUDIES (14)].

    8.5 Geriatric Use

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

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  • 11 DESCRIPTION

    Gatifloxacin ophthalmic solution, 0.5% is a quinolone antimicrobial topical ophthalmic solution for the treatment of bacterial conjunctivitis. Its chemical name is (±) 1-Cyclopropyl-6-fluoro-8- methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. Its molecular formula is C19H22FN3O4and its molecular weight is 375.40. Its chemical structure is:

    Gatifloxacin

    Gatifloxacin ophthalmic solution, 0.5% is a pale yellow colored transparent, sterile, liquid with an osmolality of 260 to 330 mOsm/kg and a pH of 5.1 to 5.7.

    Gatifloxacin ophthalmic solution, 0.5% contains the active ingredient gatifloxacin 0.5% (5 mg/mL) and the inactive ingredients benzalkonium chloride 0.005%, edetate disodium, sodium chloride and water for injection. Gatifloxacin ophthalmic solution, 0.5% may contain hydrochloric acid and/or sodium hydroxide to adjust pH.

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  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Gatifloxacin is a quinolone antimicrobial [see Microbiology (12.4)].

    12.3 Pharmacokinetics

    Gatifloxacin ophthalmic solution 0.5% was administered to one eye of 6 healthy male subjects each in an escalated dosing regimen starting with a single 2 drop dose, then 2 drops 4 times daily for 7 days, and finally 2 drops 8 times daily for 3 days. At all time points, serum gatifloxacin levels were below the lower limit of quantification (5 ng/mL) in all subjects.

    12.4 Microbiology

    Gatifloxacin is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of gatifloxacin results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action of fluoroquinolones including gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.

    Resistance to gatifloxacin in vitro develops via multiple-step mutations. Resistance to gatifloxacin in vitro occurs at a general frequency of 1 x 10-7 to 10-10.

    Gatifloxacin has been shown to be active against most isolates of the following organisms both microbiologically and clinically, in conjunctival infections:

    • Aerobic gram-positive bacteria:

    Staphylococcus aureus

    Staphylococcus epidermidis

    Streptococcus mitis group*

    Streptococcus oralis*

    Streptococcus pneumoniae

    • Aerobic gram-negative bacteria:

    Haemophilus influenzae

    *Efficacy for these organisms were studied in fewer than 10 infections.

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  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis

    There was no increase in neoplasms among B6C3F1 mice given gatifloxacin in the diet for 18 months at doses averaging 81 mg/kg/day in males and 90 mg/kg/day in females. These doses are approximately 175-fold higher than the maximum recommended ophthalmic dose (MRHOD) of 0.04 mg/kg/day gatifloxacin ophthalmic solution, 0.5% in a 60 kg human (on a mg/m2 basis).

    A statistically significant increase in the incidence of large granular lymphocyte (LGL) leukemia was seen in male rats treated with 100 mg/kg/day (approximately 405-fold higher than the MRHOD, on a mg/m2 basis). Fischer 344 rats have a high spontaneous background rate of LGL leukemia and the incidence in high-dose males only slightly exceeded the historical control range established for this strain. There was no increase in neoplasms among Fischer 344 rats given gatifloxacin in the diet for 2 years at doses averaging 47 mg/kg/day in males and 139 mg/kg/day in females (approximately 190- and 560-fold higher than the MRHOD, respectively), on a mg/m2 basis.

    Mutagenesis

    In genetic toxicity tests, gatifloxacin was positive in 1 of 5 strains used in bacterial reverse mutation assays: Salmonella strain TA102. Gatifloxacin was positive in in vitro mammalian cell mutation and chromosome aberration assays. Gatifloxacin was positive in in vitro unscheduled DNA synthesis in rat hepatocytes but not human leukocytes. Gatifloxacin was negative in in vivo micronucleus tests in mice, cytogenetics test in rats, and DNA repair test in rats. The genotoxic findings are similar to findings obtained with other quinolones and may be due to the pharmacologic inhibitory effects of high concentrations of gatifloxacin on eukaryotic type II DNA topoisomerase.

    Impairment of Fertility

    Oral administration of gatifloxacin produced no adverse effects on fertility or reproduction in rats at doses up to 200 mg/kg/day (approximately 800-fold higher than the MRHOD, on a mg/m2 basis).

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  • 14 CLINICAL STUDIES

    In two randomized, double-masked, multicenter clinical trials, where patients 1 to 89 years of age were dosed for 5 days, gatifloxacin ophthalmic solution, 0.5% was clinically superior to its vehicle on day 6 in patients with conjunctivitis and positive conjunctival cultures. Clinical outcomes for the trials demonstrated clinical success (resolution of conjunctival hyperemia and conjunctival discharge) in 58% (193/333) of patients for the gatifloxacin-treated groups versus 45% (148/325) for the vehicle-treated groups. Microbiological outcomes for the same clinical trials demonstrated a statistically superior eradication rate for causative pathogens of 90% (301/333) for gatifloxacin vs. 70% (228/325) for vehicle. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.

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  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Gatifloxacin Ophthalmic Solution, 0.5% is supplied sterile in a 5 mL white, low density polyethylene (LDPE) bottle fitted with a white low density polyethylene (LDPE) nozzle and sealed with a tan colored high density polyethylene (HDPE) cap in the following size:

    2.5 mL in 5 mL bottle: NDC 68180-435-01

    Storage

    Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.

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  • 17 PATIENT COUNSELING INFORMATION

    Avoiding Contamination of the Product

    Instruct patients to avoid contaminating the applicator tip with material from the eye, fingers, or other source.

    Potential for Hypersensitivity Reactions

    Advise patients to discontinue use immediately and contact the physician at the first sign of a rash or hypersensitivity reaction [see WARNINGS AND PRECAUTIONS (5.1) and CONTRAINDICATION (4)].

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  • SPL UNCLASSIFIED SECTION

    Manufactured for:

    Lupin Pharmaceuticals, Inc.

    Baltimore, Maryland 21202

    United States

    Manufactured by:

    Lupin Limited

    Pithampur (M. P.), 454 775

    India

    December 2016                                                                                               ID #: 249094

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  • PRINCIPAL DISPLAY PANEL

    GATIFLOXACIN OPHTHALMIC SOLUTION

    Rx Only

    0.5%

    NDC 68180-435-01

    2.5 mL Bottle Label

    GATIFLOXACIN OPHTHALMIC SOLUTION
Rx Only
0.5%
NDC 68180-435-01
							2.5 mL Bottle Pack

    GATIFLOXACIN OPHTHALMIC SOLUTION

    Rx Only

    0.5%

    NDC 68180-435-01

    2.5 mL Carton Label

    GATIFLOXACIN OPHTHALMIC SOLUTION
Rx Only
0.5%
NDC 68180-435-01
							2.5 mL Carton Label
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  • INGREDIENTS AND APPEARANCE
    GATIFLOXACIN 
    gatifloxacin solution/ drops
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68180-435
    Route of Administration OPHTHALMIC
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    GATIFLOXACIN (UNII: L4618BD7KJ) (GATIFLOXACIN ANHYDROUS - UNII:81485Y3A9A) GATIFLOXACIN 5 mg  in 1 mL
    Inactive Ingredients
    Ingredient Name Strength
    BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)  
    EDETATE DISODIUM (UNII: 7FLD91C86K)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    WATER (UNII: 059QF0KO0R)  
    Product Characteristics
    Color YELLOW (PALE YELLOW) Score     
    Shape Size
    Flavor Imprint Code
    Contains     
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:68180-435-01 1 in 1 CARTON 10/01/2013
    1 2.5 mL in 1 BOTTLE; Type 0: Not a Combination Product
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA202653 10/01/2013
    Labeler - Lupin Pharmaceuticals, Inc. (089153071)
    Registrant - LUPIN LIMITED (675923163)
    Establishment
    Name Address ID/FEI Business Operations
    LUPIN LIMITED 863645527 manufacture(68180-435) , pack(68180-435)
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