DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Zymar (Gatifloxacin Ophthalmic) - Description and Clinical Pharmacology

 
 



ZYMAR®
(gatifloxacin ophthalmic solution) 0.3%

sterile

DESCRIPTION

ZYMAR® (gatifloxacin ophthalmic solution) 0.3% is a sterile ophthalmic solution. It is an 8-methoxy fluoroquinolone anti-infective for topical ophthalmic use.

Structure and Empirical Formula:

Chemical Name:

(±)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid sesquihydrate.

Contains: Active: gatifloxacin 0.3% (3 mg/mL). Preservative: benzalkonium chloride 0.005%. Inactives: edetate disodium; purified water and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH to approximately 6.

ZYMAR® is a sterile, clear, pale yellow colored isotonic unbuffered solution. It has an osmolality of 260-330 mOsm/kg.

CLINICAL PHARMACOLOGY

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 between 1 x 10-7 to 10-10.

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

Aerobes, Gram-Positive:
Corynebacterium propinquum [Efficacy for this organism was studied in fewer than 10 infections.]
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus mitis
Streptococcus pneumoniae

Aerobes, Gram-Negative:
Haemophilus influenzae

The following in vitro data are available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of ZYMAR® in treating ophthalmic infections due to the following organisms have not been established in adequate and well-controlled clinical trials.

The following 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 following list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Gatifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2μg/mL or less (systemic susceptible breakpoint) against most (≥90%) strains of the following ocular pathogens.

Aerobes, Gram-Positive:
Listeria monocytogenes
Staphylococcus saprophyticus
Streptococcus agalactiae
Streptococcus pyogenes
Streptococcus viridans Group
Streptococcus Groups C, F, G

Aerobes, Gram-Negative:
Acinetobacter lwoffii
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Citrobacter freundii
Citrobacter koseri
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Moraxella catarrhalis
Morganella morganii
Neisseria gonorrhoeae
Neisseria meningitidis
Proteus mirabilis
Proteus vulgaris
Serratia marcescens
Vibrio cholerae
Yersinia enterocolitica

Other Microorganisms:
Chlamydia pneumoniae
Legionella pneumophila
Mycobacterium marinum
Mycobacterium fortuitum
Mycoplasma pneumoniae

Anaerobic Microorganisms:
Bacteroides fragilis
Clostridium perfringens

Clinical Studies:

In a randomized, double-masked, multicenter clinical trial, where patients were dosed for 5 days, ZYMAR® solution was superior to its vehicle on day 5-7 in patients with conjunctivitis and positive conjunctival cultures. Clinical outcomes for the trial demonstrated clinical cure of 77% (40/52) for the gatifloxacin treated group versus 58% (28/48) for the placebo treated group. Microbiological outcomes for the same clinical trial demonstrated a statistically superior eradication rate for causative pathogens of 92% (48/52) for gatifloxacin vs. 72% (34/48) for placebo. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.

ANIMAL PHARMACOLOGY

Quinolone antibacterials have been shown to cause bone or cartilage changes in immature animals. There was no evidence of bone cartilage changes following ocular administration of gatifloxacin in rabbits or dogs.

Rx only

© 2004 Allergan, Inc.

Irvine, CA 92612, U.S.A.
® Marks owned by Allergan, Inc.
Licensed from Kyorin Pharmaceuticals Co., Ltd.
U.S. PAT. 4,980,470; 5,880,283

9415X
71706US12P

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017