Floxin Information
Floxin (Ofloxacin) Description
Floxin (Ofloxacin) Otic SINGLES™ (ofloxacin otic) solution 0.3% is a
sterile aqueous anti-infective (anti-bacterial) solution for otic use.
Chemically, ofloxacin has three condensed 6-membered rings made up of a
fluorinated carboxyquinolone with a benzoxazine ring. The chemical name of
ofloxacin is:
(±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido
[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid. The empirical formula of ofloxacin
is CHFNO and its molecular weight is 361.38.
The structural formula is:
Floxin (Ofloxacin) Otic SINGLES™ contains 0.3% (3mg/mL) ofloxacin
with benzalkonium chloride (0.0025%), sodium chloride (0.9%), and water for
injection. Hydrochloric acid and sodium hydroxide are added to adjust the pH to
6.5 ± 0.5.
Floxin (Ofloxacin) Clinical Pharmacology
Ofloxacin has been shown to be active against most isolates of the following
microorganisms, both and clinically in otic
infections as described in the
section.
Floxin (Ofloxacin) Indications And Usage
Floxin (Ofloxacin) Otic SINGLES™ (ofloxacin otic)
solution 0.3% is indicated for the treatment of infections caused by susceptible
isolates of the designated microorganisms in the specific conditions listed
below:
Floxin (Ofloxacin) Contraindications
Floxin (Ofloxacin) Otic SINGLES™ (ofloxacin otic) solution 0.3% is
contraindicated in patients with a history of hypersensitivity to ofloxacin, to
other quinolones, or to any of the components in this medication.
Floxin (Ofloxacin) Warnings
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.
Floxin (Ofloxacin) Precautions
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.
Prior to administration of Floxin (Ofloxacin) Otic
SINGLES™, the solution should be warmed by holding the single-dispensing
container(s) 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 medication should be instilled. This position
should be maintained for five minutes to facilitate penetration of the
medication into the ear canal. Repeat, if necessary, for the opposite ear (see
).
Prior to administration of Floxin (Ofloxacin) Otic
SINGLES™, the solution should be warmed by holding the single-dispensing
container(s) 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 medication should be instilled. The tragus
should then be pumped 4 times by pushing inward to facilitate penetration of the
medication into the middle ear. This position should be maintained for five
minutes. Repeat, if necessary, for the opposite ear (see ).
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 (Ofloxacin) Otic twice per 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.
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.
Floxin (Ofloxacin) Adverse Reactions
In the Phase III clinical trials performed in support of
once-daily dosing, 799 subjects with otitis externa and intact tympanic
membranes were treated with ofloxacin otic solution. The studies, which served
as the basis for approval, were 020 (pediatric, adolescents and adults), 016
(adolescents and adults) and 017 (pediatric). The following treatment-related
adverse events occurred in two or more of the subjects:
†Studies 002/003 (BID) and 016/017 (QD) were
active-controlled and comparative.
Study 020 (QD) was open and non-comparative.
An unexpected increased incidence of application site reaction was seen in
studies 016/017 and was similar for both ofloxacin and the active control drug
(neomycin-polymyxin B sulfate-hydrocortisone). This finding is believed to be
the result of specific questioning of the subjects regarding the incidence of
application site reactions.
In once daily dosing studies, there were also single reports of nausea,
seborrhea, transient loss of hearing, tinnitus, otitis externa, otitis media,
tremor, hypertension and fungal infection.
In twice daily dosing studies, the following treatment-related adverse events
were each reported in a single subject: dermatitis, eczema, erythematous rash,
follicular rash, hypoaesthesia, tinnitus, dyspepsia, hot flushes, flushing and
otorrhagia.
In Phase III clinical trials which formed the basis for approval,
the following treatment-related adverse events occurred in 1% or more of the 656
subjects with non-intact tympanic membranes in AOM TT or CSOM treated
twice-daily with ofloxacin otic solution:
Other treatment-related adverse reactions reported in subjects with
non-intact tympanic membranes included: diarrhea (0.6%), nausea (0.3%), vomiting
(0.3%), dry mouth (0.5%), headache (0.3%), vertigo (0.5%), otorrhagia (0.6%),
tinnitus (0.3%), fever (0.3%). The following treatment-related adverse events
were each reported in a single subject: application site reaction, otitis
externa, urticaria, abdominal pain, dysaesthesia, hyperkinesia, halitosis,
inflammation, pain, insomnia, coughing, pharyngitis, rhinitis, sinusitis, and
tachycardia.
Cases of uncommon transient neuropsychiatric disturbances have
been included in spontaneous post-marketing reports. A causal relationship with
ofloxacin otic solution 0.3% is unknown.
Floxin (Ofloxacin) How Supplied
Floxin (Ofloxacin) Otic SINGLES™ (ofloxacin otic)
solution 0.3% is supplied in plastic single-dispensing containers, 0.25 mL each
packaged 2 per foil pouch.
NDC 54868-4327-0 Floxin (Ofloxacin) ® Otic SINGLES™, 5 foil pouches containing 2
single-dispensing containers (5 mL net volume), per carton.
Rx Only
DAIICHI PHARMACEUTICAL CORPORATION
Montvale, NJ 07645
Rev: April 2005
Covered by U.S. Patent No. 5,401,741
Floxin (Ofloxacin)
Floxin (Ofloxacin) Principal Display Panel
Floxin (Ofloxacin) Otic SINGLES™ (ofloxacin otic) solution 0.3%
