NOT FOR OPHTHALMIC USE.
NOT FOR INJECTION.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to ofloxacin is suspected, stop the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management, including intubation, should be administered as clinically indicated.
General: As with other anti-infective preparations, prolonged use may result in over-growth of nonsusceptible organisms, including fungi. If the infection is not improved after one week, cultures should be obtained to guide further treatment. If otorrhea persists after a full course of therapy, or if two or more episodes of otorrhea occur within six months, further evaluation is recommended to exclude an underlying condition such as cholesteatoma, foreign body, or a tumor.
The systemic administration of quinolones, including ofloxacin at doses much higher than given or absorbed by the otic route, has led to lesions or erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species.
Young growing guinea pigs dosed in the middle ear with 0.3% ofloxacin otic solution showed no systemic effects, lesions or erosions of the cartilage in weightbearing joints, or other signs of arthropathy. No drug-related structural or functional changes of the cochlea and no lesions in the ossicles were noted in the guinea pig following otic administration of 0.3% ofloxacin for one month.
No signs of local irritation were found when 0.3% ofloxacin was applied topically in the rabbit eye. Ofloxacin was also shown to lack dermal sensitizing potential in the guinea pig maximization study.
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, the sister chromatid exchange assay (Chinese hamster and human cell lines), the unscheduled DNA synthesis (UDS) assay using human fibroblasts, the dominant lethal assay, or the mouse micronucleus assay. Ofloxacin was positive in the rat hepatocyte UDS assay, and in the mouse lymphoma assay. In rats, ofloxacin did not affect male or female reproductive performance at oral doses up to 360 mg/kg/day. This would be over 1000 times the maximum recommended clinical dose, based upon body surface area, assuming total absorption of ofloxacin from the ear of a patient treated with FLOXIN® Otic twice per day.
Teratogenic effects: Pregnancy Category C.Ofloxacin has been shown to have an embryocidal effect in rats at a dose of 810 mg/kg/day and in rabbits at 160 mg/kg/day.
These dosages resulted in decreased fetal body weights 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.
Ofloxacin has not been shown to have any adverse effects on the developing embryo or fetus at doses relevant to the amount of ofloxacin that will be delivered ototopically at the recommended clinical doses.
Nonteratogenic Effects: Additional studies in the rat demonstrated that doses up to 360 mg/kg/day during late gestation had no adverse effects 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. FLOXIN® Otic SINGLES™ (ofloxacin otic 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 otic 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 efficacy have been demonstrated in pediatric patients of the following ages for the listed indications:
- six months and older: otitis externa with intact tympanic membranes
- one year and older: acute otitis media with tympanostomy tubes
- twelve years and older: chronic suppurative otitis media with perforated
Safety and efficacy in pediatric patients below these ages have not been established. Although no data are available on the patients less than age 6 months, there are no known safety concerns or differences in the disease process in this population that will preclude use of this product.
No changes in hearing function occurred in 30 pediatric subjects treated with ofloxacin otic and tested for audiometric parameters.
Although quinolones, including ofloxacin, have been shown to cause arthropathy in immature animals after systemic administration, young growing guinea pigs dosed in the middle ear with 0.3% ofloxacin otic solution for one month showed no systemic effects, quinolone-induced lesions, erosions of the cartilage in weight-bearing joints, or other signs of arthropathy.