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
weight-bearing 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.
Information for Patients
Avoid contaminating the applicator tip with material from the
fingers or other sources. This precaution is necessary if the sterility of the
drops is to be preserved. 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.
Otitis Externa
Prior to administration of Ofloxacin Otic Solution, the solution
should be warmed by holding the bottle in the hand for one or two minutes to
avoid dizziness which may result from the instillation of a cold solution. The
patient should lie with the affected ear upward, and then the drops should be
instilled. This position should be maintained for five minutes to facilitate
penetration of the drops into the ear canal. Repeat, if necessary, for the
opposite ear (see DOSAGE AND ADMINISTRATION).
Acute Otitis Media and Chronic Suppurative Otitis
Media
Prior to administration of Ofloxacin Otic Solution, the solution
should be warmed by holding the bottle in the hand for one or two minutes to
avoid dizziness which may result from the instillation of a cold solution. The
patient should lie with the affected ear upward, and then the drops should be
instilled. The tragus should then be pumped 4 times by pushing inward to
facilitate penetration of the drops into the middle ear. This position should be
maintained for five minutes. Repeat, if necessary, for the opposite ear (see
DOSAGE AND ADMINISTRATION).
Drug Interactions
Specific drug interaction studies have not been conducted with
Ofloxacin Otic Solution.
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 Ofloxacin Otic Solution twice per day.
PregnancyTeratogenic 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. 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
tympanic membranes.
Safety and efficacy in pediatric patients below these ages have not been
established.
Although no data are available on patients less than 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 ocurred 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.
