ZYMAXID™ (gatifloxacin ophthalmic solution) 0.5%

DESCRIPTION

ZYMAXID™ sterile ophthalmic solution is an 8-methoxyfluoroquinolone anti-infective for the treatment of bacterial conjunctivitis. Its chemical name is (±)-1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid, sesquihydrate.

ZYMAXID™ is a clear, pale yellow, sterile, preserved aqueous solution with an osmolality of 260-330 mOsm/kg and a pH of 5.1-5.7.

ZYMAXID™ contains Active: gatifloxacin 0.5% (5 mg/mL); Inactives: benzalkonium chloride 0.005%; edetate disodium; purified water; and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH.

Pharmacokinetics
Gatifloxacin ophthalmic solution 0.3% or 0.5% was administered to one eye of 6 healthy male subjects each in an escalated dosing regimen starting with a single 2 drop dose, then 2 drops 4 times daily for 7 days, and finally 2 drops 8 times daily for 3 days. At all time points, serum gatifloxacin levels were below the lower limit of quantification (5 ng/mL) in all subjects.

Microbiology
Gatifloxacin is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of gatifloxacin results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action of fluoroquinolones including gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.

Resistance to gatifloxacin in vitro develops via multiple-step mutations. Resistance to gatifloxacin in vitro occurs at a general frequency of 1 x 10-7 to 10-10.

Gatifloxacin has been shown to be active against most isolates of the following organisms both microbiologically and clinically, in conjunctival infections as described in the INDICATIONS AND USAGE.

Aerobic Gram-Positive Bacteria:
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus mitis group*
Streptococcus oralis*
Streptococcus pneumoniae

Aerobic Gram-Negative Bacteria:
Haemophilus influenzae

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

ZYMAXID™ ophthalmic solution is a topical fluoroquinolone anti-infective indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

Haemophilus influenzae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis group*, Streptococcus oralis*, Streptococcus pneumoniae

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

None

Avoidance of Contact Lenses. Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with ZYMAXID™

Most common adverse reactions occurring in >/= 1 % of patients included worsening of conjunctivitis, eye irritation, dysgeusia, and eye pain.

To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Patients 1 year of age or older: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times on Day 1. Instill one drop two to four times daily in the affected eye(s) while awake on Days 2 through 7.

5 mL size bottle filled with 2.5 mL of gatifloxacin ophthalmic solution, 0.5%.