Included as part of the PRECAUTIONS section.
Topical Ophthalmic Use Only
ZYMAXID® solution should not be introduced directly into
the anterior chamber of the eye.
Growth Of Resistant Organisms With Prolonged Use
As with other anti-infectives, prolonged use of ZYMAXID® (gatifloxacin
ophthalmic solution) 0.5% may result in overgrowth of nonsusceptible 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.
Avoidance Of Contact Lens Wear
Patients should be advised not to wear contact lenses if
they have signs and symptoms of bacterial conjunctivitis or during the course
of therapy with ZYMAXID® (see PATIENT INFORMATION).
Carcinogenesis, Mutagenesis, Impairment Of Fertility
There was no increase in neoplasms among B6C3F1 mice
given gatifloxacin in the diet for 18 months at doses averaging 81 mg/kg/day in
males and 90 mg/kg/day in females. These doses are approximately 1600-fold and
1800-fold higher, respectively, than the maximum recommended ophthalmic dose of
0.05 mg/kg/day in a 50 kg human.
There was no increase in neoplasms among Fischer 344 rats
given gatifloxacin in the diet for 2 years at doses averaging 47 mg/kg/day in
males and 139 mg/kg/day in females (900- and 2800-fold higher, respectively,
than the maximum recommended ophthalmic dose). A statistically significant
increase in the incidence of large granular lymphocyte (LGL) leukemia was seen
in males treated with a high dose of approximately 2000-fold higher than the
maximum recommended ophthalmic dose. Fischer 344 rats have a high spontaneous background
rate of LGL leukemia and the incidence in high-dose males only slightly
exceeded the historical control range established for this strain.
In genetic toxicity tests, gatifloxacin was positive in 1
of 5 strains used in bacterial reverse mutation assays: Salmonella strain
TA102. Gatifloxacin was positive in in vitro mammalian cell mutation and
chromosome aberration assays. Gatifloxacin was positive in in vitro unscheduled
DNA synthesis in rat hepatocytes but not human leukocytes. Gatifloxacin was negative
in in vivo micronucleus tests in mice, cytogenetics test in rats, and DNA
repair test in rats. The findings may be due to the inhibitory effects of high
concentrations on eukaryotic type II DNA topoisomerase.
There were no adverse effects on fertility or
reproduction in rats given gatifloxacin orally at doses up to 200 mg/kg/day
(approximately 4000-fold higher than the maximum recommended ophthalmic dose
for ZYMAXID® ).
Use In Specific Populations
Pregnancy Category C
There were no teratogenic effects observed in rats or
rabbits following oral gatifloxacin doses up to 50 mg/kg/day (approximately
1000-fold higher than the maximum recommended ophthalmic dose). However,
skeletal/craniofacial malformations or delayed ossification, atrial
enlargement, and reduced fetal weight were observed in fetuses from rats given
≥ 150 mg/kg/day (approximately 3000-fold higher than the maximum
recommended ophthalmic dose). In a perinatal/postnatal study, increased late
post-implantation loss and neonatal/perinatal mortalities were observed at 200
mg/kg/day (approximately 4000-fold higher than the maximum recommended
Because there are no adequate and well-controlled studies
in pregnant women, ZYMAXID® solution should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Gatifloxacin is excreted in the breast milk of rats. It
is not known whether this drug is excreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when ZYMAXID® is
administered to a nursing woman.
The safety and effectiveness of ZYMAXID® in infants below
one year of age have not been established. ZYMAXID® has been demonstrated in
clinical trials to be safe and effective for the treatment of bacterial
conjunctivitis in pediatric patients one year or older (see Clinical Studies).
No overall differences in safety or effectiveness have
been observed between elderly and younger patients.