Label: OFLOXACIN solution

  • NDC Code(s): 60505-0560-0, 60505-0560-1
  • Packager: Apotex Corp.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated February 13, 2019

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  • DESCRIPTION

    Ofloxacin ophthalmic solution, USP 0.3% is a sterile ophthalmic solution. It is a fluorinated carboxyquinolone anti-infective for topical ophthalmic use.

    Chemical Name: (±)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid.

    ofloxacin-01

    Contains: Active: Ofloxacin 0.3% (3 mg/mL)

    Preservative: Benzalkonium chloride 0.005%; Inactives: Hydrochloric acid, sodium chloride and water for injection. Sodium hydroxide may be added to adjust the pH.

    Ofloxacin ophthalmic solution, USP 0.3% is unbuffered and formulated with a pH of 6.4 (range - 6.0 to 6.8). It has an osmolality of 300 mOsm/kg. Ofloxacin is a fluorinated 4-quinolone which differs from other fluorinated 4-quinolones in that there is a six member (pyridobenzoxazine) ring from positions 1 to 8 of the basic ring structure.

  • CLINICAL PHARMACOLOGY

    Pharmacokinetics

    Serum, urine and tear concentrations of ofloxacin were measured in 30 healthy women at various time points during a ten-day course of treatment with ofloxacin ophthalmic solution. The mean serum ofloxacin concentration ranged from 0.4 ng/mL to 1.9 ng/mL. Maximum ofloxacin concentration increased from 1.1 ng/mL on day one to 1.9 ng/mL on day 11 after QID dosing for 10 1/2 days. Maximum serum ofloxacin concentrations after ten days of topical ophthalmic dosing were more than 1,000 times lower than those reported after standard oral doses of ofloxacin.

    Tear ofloxacin concentrations ranged from 5.7 to 31 mcg/g during the 40 minute period following the last dose on day 11. Mean tear concentration measured four hours after topical ophthalmic dosing was 9.2 mcg/g.

    Corneal tissue concentrations of 4.4 mcg/mL were observed four hours after beginning topical ocular application of two drops of ofloxacin ophthalmic solution every 30 minutes. Ofloxacin was excreted in the urine primarily unmodified.

    Microbiology

    Ofloxacin has in vitro activity against a broad range of gram-positive and gram-negative aerobic and anaerobic bacteria. Ofloxacin is bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Ofloxacin is thought to exert a bactericidal effect on susceptible bacterial cells by inhibiting DNA gyrase, an essential bacterial enzyme which is a critical catalyst in the duplication, transcription, and repair of bacterial DNA.

    Cross-resistance has been observed between ofloxacin and other fluoroquinolones. There is generally no cross-resistance between ofloxacin and other classes of antibacterial agents such as beta-lactams or aminoglycosides.

    Ofloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically, in conjunctival and/or corneal ulcer infections (see Indications and Usage).

    *Efficacy for this organism was studied in fewer than 10 infections

    AEROBES, GRAM-POSITIVEAEROBES, GRAM-NEGATIVE
        Staphylococcus aureus    Enterobacter cloacae
        Staphylococcus epidermidis    Haemophilus influenzae
        Streptococcus pneumoniae    Proteus mirabilis
    ANAEROBIC SPECIES    Pseudomonas aeruginosa
        Propionibacterium acnes    Serratia marcescens*

    The safety and effectiveness of ofloxacin ophthalmic solution in treating ophthalmologic infections due to the following organisms have not been established in adequate and well-controlled clinical trials. Ofloxacin ophthalmic solution has been shown to be active in vitro against most strains of these organisms but the clinical significance in ophthalmologic infections is unknown.

    AEROBES, GRAM-POSITIVE
        Enterococcus faecalis    Staphylococcus hominus
        Listeria monocytogenes    Staphylococcus simulans
        Staphylococcus capitis    Streptococcus pyogenes
    AEROBES, GRAM-NEGATIVE
        Acinetobacter calcoaceticus var. anitratus    Klebsiella pneumoniae
        Acinetobacter calcoaceticus var. lwoffii    Moraxella (Branhamella) catarrhalis
        Citrobacter diversus    Moraxella lacunata
        Citrobacter freundii    Morganella morganii
        Enterobacter aerogenes    Neisseria gonorrhoeae
        Enterobacter agglomerans    Pseudomonas acidovorans
        Escherichia coli    Pseudomonas fluorescens
        Haemophilus parainfluenzae    Shigella sonnei
        Klebsiella oxytoca
    OTHER
        Chlamydia trachomatis

    Clinical Studies

    Conjunctivitis

    In a randomized, double-masked, multicenter clinical trial, ofloxacin ophthalmic solution was superior to its vehicle after 2 days of treatment in patients with conjunctivitis and positive conjunctival cultures. Clinical outcomes for the trial demonstrated a clinical improvement rate of 86% (54/63) for the ofloxacin treated group versus 72% (48/67) for the placebo treated group after 2 days of therapy. Microbiological outcomes for the same clinical trial demonstrated an eradication rate for causative pathogens of 65% (41/63) for the ofloxacin treated group versus 25% (17/67) for the vehicle treated group after 2 days of therapy. Please note that microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.

    Corneal Ulcers

    In a randomized, double-masked, multi-center clinical trial of 140 subjects with positive cultures, ofloxacin ophthalmic solution treated subjects  had an overall clinical success rate (complete re-epithelialization and no progression of the infiltrate for two consecutive visits) of 82% (61/74) compared to 80% (53/66) for the fortified antibiotic group, consisting of 1.5% tobramycin and 10% cefazolin solutions. The median time to clinical success was 11 days for the ofloxacin treated group and 10 days for the fortified treatment group.

  • INDICATIONS AND USAGE

    Ofloxacin ophthalmic solution is indicated for the treatment of infections caused by susceptible strains of the following bacteria in the conditions listed below:

    *Efficacy for this organism was studied in fewer than 10 infections

    CONJUNCTIVITIS
        Gram-positive bacteria    Gram-negative bacteria
            Staphylococcus aureus        Enterobacter cloacae
            Staphylococcus epidermidis        Haemophilus influenzae
            Streptococcus pneumoniae        Proteus mirabilis
            Pseudomonas aeruginosa
    CORNEAL ULCERS
        Gram-positive bacteria    Gram-negative bacteria
            Staphylococcus aureus        Pseudomonas aeruginosa
            Staphylococcus epidermidis        Serratia marcescens*
            Streptococcus pneumoniae    Anaerobic species:
            Propionibacterium acnes
  • CONTRAINDICATIONS

    Ofloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to ofloxacin, to other quinolones, or to any of the components in this medication (see Warnings).

  • WARNINGS

    NOT FOR INJECTION.

    Ofloxacin ophthalmic solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.

    There are rare reports of anaphylactic reaction/shock and fatal hypersensitivity reactions in patients receiving systemic quinolones, some following the first dose, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. A rare occurrence of Stevens-Johnson syndrome, which progressed to toxic epidermal necrolysis, has been reported in a patient who was receiving topical ophthalmic ofloxacin. If an allergic reaction to ofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management, including intubation should be administered as clinically indicated.  

  • PRECAUTIONS

    General

    As with other anti-infectives, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. Ofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction.

    The systemic administration of quinolones, including ofloxacin, has led to lesions or erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species. Ofloxacin, administered systemically at 10 mg/kg/day in young dogs (equivalent to 110 times the maximum recommended daily adult ophthalmic dose) has been associated with these types of effects.

    Information for Patients

    Avoid contaminating the applicator tip with material from the eye, fingers or other source.

    Systemic quinolones, including ofloxacin, have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.

    Drug Interactions

    Specific drug interaction studies have not been conducted with ofloxacin ophthalmic solution. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Long term studies to determine the carcinogenic potential of ofloxacin have not been conducted.

    Ofloxacin was not mutagenic in the Ames test, in vitro and in vivo cytogenic assay, sister chromatid exchange assay (Chinese hamster and human cell lines), unscheduled DNA synthesis (UDS) assay using human fibroblasts, the dominant lethal assay, or mouse micronucleus assay. Ofloxacin was positive in the UDS test using rat hepatocyte, and in the mouse lymphoma assay.

    In fertility studies in rats, ofloxacin did not affect male or female fertility or morphological or reproductive performance at oral dosing up to 360 mg/kg/day (equivalent to 4,000 times the maximum recommended daily ophthalmic dose).

    Pregnancy

    Teratogenic Effects

    Ofloxacin has been shown to have an embryocidal effect in rats and in rabbits when given in doses of 810 mg/kg/day (equivalent to 9,000 times the maximum recommended daily ophthalmic dose) and 160 mg/kg/day (equivalent to 1,800 times the maximum recommended daily ophthalmic dose). These dosages resulted in decreased fetal body weight and increased fetal mortality in rats and rabbits, respectively. Minor fetal skeletal variations were reported in rats receiving doses of 810 mg/kg/day. Ofloxacin has not been shown to be teratogenic at doses as high as 810 mg/kg/day and 160 mg/kg/day when administered to pregnant rats and rabbits, respectively.

    Nonteratogenic Effects

    Additional studies in rats with doses up to 360 mg/kg/day during late gestation showed no adverse effect on late fetal development, labor, delivery, lactation, neonatal viability, or growth of the newborn.

    There are, however, no adequate and well-controlled studies in pregnant women. Ofloxacin ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

    Nursing Mothers

    In nursing women a single 200 mg oral dose resulted in concentrations of ofloxacin in milk which were similar to those found in plasma. It is not known whether ofloxacin is excreted in human milk following topical ophthalmic administration. Because of the potential for serious adverse reactions from ofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

    Pediatric Use

    Safety and effectiveness in infants below the age of one year have not been established.

    Quinolones, including ofloxacin, have been shown to cause arthropathy in immature animals after oral administration; however, topical ocular administration of ofloxacin to immature animals has not shown any arthropathy. There is no evidence that the ophthalmic dosage form of ofloxacin has any effect on weight-bearing joints.

    Geriatric Use

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

  • ADVERSE REACTIONS

    Ophthalmic Use

    The most frequently reported drug-related adverse reaction was transient ocular burning or discomfort. Other reported reactions include stinging, redness, itching, chemical conjunctivitis/keratitis, ocular/periocular/facial edema, foreign body sensation, photophobia, blurred vision, tearing, dryness, and eye pain. Rare reports of dizziness and nausea have been received.

    Refer to Warnings for additional adverse reactions.

  • DOSAGE AND ADMINISTRATION

    The recommended dosage regimen for the treatment of bacterial conjunctivitis is:

    Days 1 and 2Instill one to two drops every two to four hours in the affected eye(s).
    Days 3 through 7Instill one to two drops four times daily.
    The recommended dosage regimen for the treatment of bacterial corneal ulcer is:
    Days 1 and 2Instill one to two drops into the affected eye every 30 minutes, while awake. Awaken at approximately four and six hours after retiring and instill one to two drops.
    Days 3 through 7 to 9Instill one to two drops hourly, while awake.
    Days 7 to 9 through
    treatment completionInstill one to two drops, four times daily.
  • HOW SUPPLIED

    Ofloxacin ophthalmic solution, USP 0.3% is supplied sterile in plastic dropper bottles with tan caps in the following sizes:

    5 mL - NDC 60505-0560-0 

    10 mL - NDC 60505-0560-1

    Store at 25°C (77°F); excursions permitted from 15 to 30°C (59 to 86°F).  Protect from light.

    APOTEX INC.
    OFLOXACIN OPHTHALMIC SOLUTION, USP 0.3%

    Manufactured by  Manufactured for
    Apotex Inc. Apotex Corp.
    Toronto, OntarioWeston, Florida
    Canada M9L 1T9USA 33326

    Revised: June 2018       

  • PRINCIPAL DISPLAY PANEL - 5 mL BOTTLE LABEL

    Representative sample of labeling (see HOW SUPPLIED section for complete listing):

    APOTEX CORP. NDC 60505-0560-0

    Ofloxacin Ophthalmic Solution USP

    0.03%

    Sterile Ophthalmic Solution

    Rx Only

    FOR TOPICAL OPHTHALMIC USE ONLY

    5 mL

    ofloxacin-bottle

  • PRINCIPAL DISPLAY PANEL - 5 mL CARTON LABEL

    Representative sample of labeling (see HOW SUPPLIED section for complete listing):

    APOTEX CORP. NDC 60505-0560-0

    Ofloxacin Ophthalmic Solution USP

    0.03%

    Sterile Ophthalmic Solution

    Rx Only

    FOR TOPICAL OPHTHALMIC USE ONLY

    5 mL

    ofloxacin-carton

  • INGREDIENTS AND APPEARANCE
    OFLOXACIN 
    ofloxacin solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:60505-0560
    Route of AdministrationOPHTHALMIC
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    OFLOXACIN (UNII: A4P49JAZ9H) (OFLOXACIN - UNII:A4P49JAZ9H) OFLOXACIN3 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    WATER (UNII: 059QF0KO0R)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:60505-0560-01 in 1 CARTON03/01/2019
    15 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product
    2NDC:60505-0560-11 in 1 CARTON03/01/2019
    210 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07651303/01/2019
    Labeler - Apotex Corp. (845263701)
    Registrant - Apotex Inc. (209429182)
    Establishment
    NameAddressID/FEIBusiness Operations
    Apotex Inc.255092496manufacture(60505-0560) , analysis(60505-0560)