Ofloxacin

OFLOXACIN- ofloxacin solution
FDC Limited

DESCRIPTION

Ofloxacin ophthalmic solution 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.

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Contains: Active: ofloxacin 0.3% (3 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.

Ofloxacin ophthalmic solution 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 1000 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 as described in the INDICATIONS AND USAGE section.

AEROBES , GRAM – POSITIVE :	AEROBES , GRAM – NEGATIVE :
Staphylococcus aureus	Enterobacter cloacae
Staphylococcus epidermidis	Haemophilus influenza
Streptococcus pneumoniae	Proteus mirabilis
ANAEROBIC SPECIES :	Pseudomonas aeruginosa
Propionibacterium acnes	Serratia marcescens *

*Efficasy for this organism was studied in fewer than 10 infection

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