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.
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).
Teratogenic 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,
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. OCUFLOX (ofloxacin ophthalmic) solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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.
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.
No overall differences in safety or effectiveness have been observed between elderly and younger patients.