Levofloxacin Information
Levofloxacin ()
Levofloxacin () Description
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 (-)-()-enantiomer of the racemic drug substance, ofloxacin. It is more soluble in water at neutral pH than ofloxacin. Its structural formula is:
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:
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.
Levofloxacin () Clinical Pharmacology
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 2.25 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 mcg/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 mcg/mL. The clinical significance of these concentrations is unknown.
Levofloxacin () is the -isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the -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 topoisomerases), enzymes required for DNA replication, transcription, repair, and recombination.
Levofloxacin () has 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 is a rare occurrence (range: 10 to 10).
Levofloxacin () has been shown to be active against most strains of the following microorganisms, both and in clinical infections as described in the section:
AEROBIC GRAM-POSITIVE MICROORGANISMS
Corynebacterium species* (Groups C/F) (Group G)Viridans group streptococci
AEROBIC GRAM-NEGATIVE MICROORGANISMS
*Efficacy for this organism was studied in fewer than 10 infections.
The following data are also available,
These organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the 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 minimal inhibitory concentrations (MICs) of 2 mcg/mL or less (systemic susceptible breakpoint) against most (≥90%) strains of the following ocular pathogens.
AEROBIC GRAM-POSITIVE MICROORGANISMS
AEROBIC GRAM-NEGATIVE MICROORGANISMS
Levofloxacin () Indications And Usage
Levofloxacin () ophthalmic solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:
Corynebacterium species* (Groups C/F) (Group G)Viridans group streptococci
*Efficacy for this organism was studied in fewer than 10 infections.
Levofloxacin () Contraindications
Levofloxacin () ophthalmic solution is contraindicated in patients with a history of hypersensitivity to Levofloxacin () , to other quinolones, or to any of the components in this medication.
Levofloxacin () Warnings
NOT FOR INJECTION.
Levofloxacin () ophthalmic solution should not be injected subconjunctivally, 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.
Levofloxacin () Precautions
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 slit-lamp biomicroscopy, and, where appropriate, fluorescein staining.
Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.
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 reaction.
In a long term carcinogenicity study in rats, Levofloxacin () exhibited no carcinogenic or tumorigenic potential following daily dietary administration for 2 years; 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 ( and ), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the mouse sister chromatid exchange assay. It was positive in the chromosomal aberration (CHL cell line) and 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.
Levofloxacin () Adverse Reactions
The most frequently reported adverse events in the overall study population 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 to 3% of patients. Other reported reactions occurring in less than 1% of patients included allergic reactions, lid edema, ocular dryness, and ocular itching.
Levofloxacin () How Supplied
Levofloxacin () ophthalmic solution, 0.5% is supplied in a white, low density polyethylene bottle with a controlled dropper tip and a tan polypropylene cap in the following size:
5 mL fill in a 10 mL capacity bottle- NDC 17478-106-10
Levofloxacin () Principal Display Panel – Ml Bottle Label
Levofloxacin () Principal Display Panel – Ml Carton Label
