General
As with other anti-infectives, prolonged use 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.
Ofloxacin should be discontinued at the first appearance of a skin rash or any
other sign of hypersensitivity reaction.
The systemic administration of quinolones, including ofloxacin, has led to
lesions or erosions of the cartilage in weight-bearing joints and other signs of
arthropathy in immature animals of various species. Ofloxacin, administered
systemically at 10 mg/kg/day in young dogs (equivalent to 110 times the maximum
recommended daily adult ophthalmic dose) has been associated with these types of
effects.
Information for patients
Avoid contaminating the applicator tip with material from the
eye, fingers or other source.
Systemic quinolones, including ofloxacin, 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.
Drug interactions
Specific drug interaction studies have not been conducted with
ofloxacin ophthalmic solution. However, the systemic administration of some
quinolones has been shown to elevate plasma concentrations of theophylline,
interfere with the metabolism of caffeine, and enhance the effects of the oral
anticoagulant warfarin and its derivatives, and has been associated with
transient elevations in serum creatinine in patients receiving cyclosporine
concomitantly.
Carcinogenesis, mutagenesis, impairment of
fertility
Long term studies to determine the carcinogenic potential of
ofloxacin have not been conducted.
Ofloxacin was not mutagenic in the Ames test, in vitro and in vivo cytogenic
assay, sister chromatid exchange assay (Chinese hamster and human cell lines),
unscheduled DNA synthesis (UDS) assay using human fibroblasts, the dominant
lethal assay, or mouse micronucleus assay. Ofloxacin was positive in the UDS
test using rat hepatocyte, and in the mouse lymphoma assay.
In fertility studies in rats, ofloxacin did not affect male or female
fertility or morphological or reproductive performance at oral dosing up to 360
mg/kg/day (equivalent to 4000 times the maximum recommended daily ophthalmic
dose).
PregnancyTeratogenic effects
Pregnancy Category C: Ofloxacin has been
shown to have an embryocidal effect in rats and in rabbits when given in doses
of 810 mg/kg/day (equivalent to 9000 times the maximum recommended daily
ophthalmic dose) and 160 mg/kg/day (equivalent to 1800 times the maximum
recommended daily ophthalmic dose). These dosages resulted in decreased fetal
body weight and increased fetal mortality in rats and rabbits, respectively.
Minor fetal skeletal variations were reported in rats receiving doses of 810
mg/kg/day. Ofloxacin has not been shown to be teratogenic at doses as high as
810 mg/kg/day and 160 mg/kg/day when administered to pregnant rats and rabbits,
respectively.
Nonteratogenic effects
Additional studies in rats with doses up to 360 mg/kg/day during
late gestation showed no adverse effect on late fetal development, labor,
delivery, lactation, neonatal viability, or growth of the newborn.
There are, however, no adequate and well-controlled studies in pregnant
women. Ofloxacin ophthalmic solution should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Nursing mothers
In nursing women a single 200 mg oral dose resulted in
concentrations of ofloxacin in milk which were similar to those found in plasma.
It is not known whether ofloxacin is excreted in human milk following topical
ophthalmic administration. Because of the potential for serious adverse
reactions from ofloxacin in nursing infants, a decision should be made whether
to discontinue nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
Pediatric use
Safety and effectiveness in infants below the age of one year
have not been established.
Quinolones, including ofloxacin, have been shown to cause arthropathy in
immature animals after oral administration; however, topical ocular
administration of ofloxacin to immature animals has not shown any arthropathy.
There is no evidence that the ophthalmic dosage form of ofloxacin has any effect
on weight bearing joints.
Geriatric use
No overall differences in safety or effectiveness have been
observed between elderly and younger patients.
