LEVOFLOXACIN by is a Prescription medication manufactured, distributed, or labeled by Rising Pharmaceuticals, Inc., Indoco Remedies Ltd.. Drug facts, warnings, and ingredients follow.
Levofloxacin Ophthalmic Solution 0.5% is a sterile topical ophthalmic solution. Levofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of Gram-positive and Gram-negative ocular pathogens. Levofloxacin is the pure (-)-(s)-enantiomer of the racemic drug substance, ofloxacin. It is more soluble in water neutral pH than ofloxacin.
Structural formula:
Levofloxacin Hemihydrate
C18H20FN3O4· ½ H2O Mol Wt. 370.38
Chemical Name:(-)-(s)-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 hemihydrate. Levofloxacin (hemihydrate) is a yellowish-white crystalline powder. Each mL of Levofloxacin Ophthalmic Solution contains 5.12 mg of levofloxacin hemihydrate equivalent to 5 mg levofloxacin.
Contains:
Active: Levofloxacin 0.5% ( mg/mL); Preservative: benzalkonium chloride 0.005%;
Inactives: sodium chloride and water for injection. May also contain
hydrochloric acid and/or sodium hydroxide to adjust pH. Levofloxacin
Ophthalmic Solution is isotonic and formulated at pH 6.5 with an
osmolality of approximately 300 mOsm/kg. Levofloxacin is a fluorinated
4-quinolone containing a six-member (pyridobenzoxazine) ring from
positions 1 to 8 of the basic ring structure.
Pharmacokinetics:
Levofloxacin concentration in plasma was measured in 15 healthy
adult volunteers at various time points during a 15 day course of
treatment with Levofloxacin Ophthalmic Solution. The mean levofloxacin
concentration in plasma 1 hour postdose, ranged from 0.86 ng/mL on Day 1
to 2.05 ng/mL on Day 15. The highest maximum mean levofloxacin
concentration of 2.5 ng/mL was measured on Day 4 following 2 days of
dosing every 2 hours for a total of 8 doses per day. Maximum mean
levofloxacin concentrations increased from 0.94 ng/mL on Day 1 to 2.15
ng/mL on Day 15, which is more than 1,000 times lower than those
reported after standard oral doses of levofloxacin. Levofloxacin
concentration in tears was measured in 30 healthy adult volunteers at
various time points following instillation of a single drop of
Levofloxacin Ophthalmic Solution. Mean levofloxacin concentrations in
tears ranged from 34.9 to 221.1 μg/mL during the 60-minute
period following the single dose. The mean tear concentrations measured
4 and 6 hours postdose were 17.0 and 6.6 μg/mL. The clinical
significance of these concentrations is unknown.
Microbiology:
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves the inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoismerases), enzymes required for DNA replication, transcription, repair, and recombination. Levofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms and is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from β-lactam antibiotics and aminoglycosides, and therefore may be active against bacteria resistant to β-lactam antibiotics and aminoglycosides. Additionally, β-lactam antibiotics and aminoglycosides may be active against bacteria resistant to levofloxacin. Resistance to levofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10-9 to 10-10). Levofloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:
AEROBIC GRAM-POSITIVE
MICROORGANISMS
Corynebacterium species*
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci
AEROBIC GRAM-NEGATIVE
MICROORGANISMS
Acinetobacter lwoffii*
Haemophilus influenzae
Serratia marcescens*
*Efficacy for this organism was studied in fewer than 10 infections. The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of levofloxacin in treating ophthalmological infections due to these microorganisms have not been established in adequate and well-controlled trials. These organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections.
Levofloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2μg/mL or less (systemic susceptible breakpoint) against most (≥90%) strains of the following ocular pathogens:
Aerobic gram-positive microorganisms
Enterococcus faecalis
Streptococcus agalactiae
Staphylococcus saprophyticus
Streptococcus pyogenes
Aerobic gram-negative microorganisms
Acinetobacter anitratus
Legionella pneumophila
Acinetobacter baumannii
Moraxella catarrhalis
Citrobacter diversusi
Morganella morgqanii
Citrobacter freudii
Neisseria gonorrhoeae
Enterobacter aerogenes
Proteus mirabilis
Enterobacter agglomerans
Proteus vulgaris
Enteroacter cloacae
Providencia rettgeri
Escherichia coli
Providencia stuartii
Haemophilus arainfluenzae
Pseudomonas aeruginosa
Klebsiella oxytoca
Pseudomonas fluorescens
Klebsiella pneumoniae
Clinical Studies:
In randomized, double-masked, multicenter controlled clinical
trial where patients were dosed for 5 days, Levofloxacin Ophthalmic
Solution demonstrated clinical cures in 79% of patients treated
for bacterial conjunctivitis on the final study visit day (day 6-10).
Microbial outcome for the same clinical trials demonstrated an
eradication rate for presumed pathogens of 90%.
Levofloxacin Ophthalmic Solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:
AEROBIC GRAM-POSITIVE MICROORGANISMS
Corynebacterium species*
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci
AEROBIC GRAM-NEGATIVE
MICROORGANISMS
Acinetobacter lwoffii*
Haemophilus influenzae
Serratia marcescens*
*Efficacy for this organism was studied in fewer than 10 infections.
NOT FOR INJECTION. Levofloxacin Ophthalmic Solution should not be injected subconjunctially, nor should it be introduced directly into the anterior chamber of the eye.
In patients receiving systemic quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
General
As with other anti-infectives, prolonged use may result in
overgrowth of non-susceptible 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 slitlamp biomicroscopy,
and where appropriate, fluorescein staining. Patients should be advised
not to wear contact lenses if they have signs and symptoms of bacterial
conjunctivitis.
Information for Patients
Avoid contaminating the applicator tip with material from the
eye, fingers or other source. Systemic quinolones 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 reactions.
Drug Interactions:
Specific drug interaction studies have not been conducted with
Levofloxacin 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 systemic cyclosporine concomitantly.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
In a long term carcinogenicity study in rats, levofloxacin exhibited no carcinogenic or tumorigenic potential following daily dietary administration; the highest dose (100 mg/kg/day) was 875 times the highest recommended human ophthalmic dose. Levofloxacin was not mutagenic in the following assays: Ames bacterial mutation assay (S. typhimurium and E. coli), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the in vivo mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and in vitro sister chromatid exchange (CHL/IU cell line) assays. Levofloxacin caused no impairment of fertility or reproduction in rats at oral doses as high as 360 mg/kg/day, corresponding to 3,150 times the highest recommended human ophthalmic dose.
Pregnancy: Teratogenic Effects. Pregnancy Category C
Levofloxacin at oral doses of 810 mg/kg/day in rats, which
corresponds to approximately 7,000 times the highest recommended human
ophthalmic dose, caused decreased fetal body weight and increased fetal
mortality. No teratogenic effect was observed when rabbits were dosed
orally as high as 50 mg/kg/day, which corresponds to approximately 400
times the highest recommended maximum human ophthalmic dose, or when
dosed intravenously as high as 25 mg/kg/day, corresponding to
approximately 200 times the highest recommended human ophthalmic dose.
There are, however, no adequate and well-controlled studies in pregnant
woman. Levofloxacin should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Nursing Mothers:
Levofloxacin has not been measured in human milk. Based upon data
from ofloxacin, it can be presumed that levofloxacin is excreted in
human milk. Caution should be exercised when Levofloxacin Ophthalmic
Solution is administered to a nursing mother.
Pediatric Use:
Safety and effectiveness in infants below the age of one year
have not been established. Oral administration of quinolones has been
shown to cause arthropathy in immature animals. There is no evidence
that the ophthalmic administration of levofloxacin has any effect on
weight bearing joints.
The most frequently reported adverse events in the overall study populations were transient decreased vision, fever, foreign body sensation, headache, transient ocular burning, ocular pain or discomfort, pharyngitis and photophobia. These events occurred in approximately 1-3% of patients. Other reported reactions occurring in less than 1% of patients included allergic reactions, lid edema, ocular dryness and ocular itching.
To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals, Inc. at 1-866-562-4597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Levofloxacin Ophthalmic Solution 0.5% is supplied in a natural, low density polyethylene bottle with a controlled dropper tip and a tan, high density polyethylene cap in the following size:
Bottles of 5 mL NDC
16571-150-50
Store at 20°-25°C
(68°-77°F)
Rx Only
Manufactured in India for:
Rising Pharmaceuticals Inc.
Allendale, NJ 07401
Distributed by:
Pack Pharmaceuticals, LLC
Allendale, NJ 07401
LEVOFLOXACIN
levofloxacin solution/ drops |
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Labeler - Rising Pharmaceuticals, Inc. (835513529) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Indoco Remedies Ltd. | 915851870 | MANUFACTURE(16571-150) |