Ofloxacin by NuCare Pharmceuticals,Inc. / NuCare Pharmaceuticals,Inc. OFLOXACIN solution
Ofloxacin by
Drug Labeling and Warnings
Ofloxacin by is a Prescription medication manufactured, distributed, or labeled by NuCare Pharmceuticals,Inc., NuCare Pharmaceuticals,Inc.. Drug facts, warnings, and ingredients follow.
Drug Details [pdf]
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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-7 H-pyrido[1,2,3- de]-1,4-benzoxazine-6-carboxylic acid.
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.
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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 vitroactivity 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 vitroand 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-POSITIVE AEROBES, 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 vitroagainst 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.
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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 ( seeWarnings).
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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.
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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 vitroand in vivocytogenic 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.
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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.
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DOSAGE AND ADMINISTRATION
The recommended dosage regimen for the treatment of bacterial conjunctivitisis:
Days 1 and 2 Instill one to two drops every two to four hours in the affected eye(s). Days 3 through 7 Instill one to two drops four times daily. The recommended dosage regimen for the treatment of bacterial corneal ulceris: Days 1 and 2 Instill 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 9 Instill one to two drops hourly, while awake. Days 7 to 9 through treatment completion Instill 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:
10 mL - NDC: 68071-3566-1
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%Revised: June 2018
- PRINCIPAL DISPLAY PANEL
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INGREDIENTS AND APPEARANCE
OFLOXACIN
ofloxacin solutionProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC: 68071-3566(NDC:60505-0560) Route of Administration OPHTHALMIC Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength OFLOXACIN (UNII: A4P49JAZ9H) (OFLOXACIN - UNII:A4P49JAZ9H) OFLOXACIN 3 mg in 1 mL Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7) HYDROCHLORIC ACID (UNII: QTT17582CB) SODIUM CHLORIDE (UNII: 451W47IQ8X) WATER (UNII: 059QF0KO0R) SODIUM HYDROXIDE (UNII: 55X04QC32I) Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC: 68071-3566-1 1 in 1 CARTON 01/30/2024 1 10 mL in 1 BOTTLE, DROPPER; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.) Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA076513 03/01/2019 Labeler - NuCare Pharmceuticals,Inc. (010632300) Establishment Name Address ID/FEI Business Operations NuCare Pharmaceuticals,Inc. 010632300 relabel(68071-3566)
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