WARNINGSNOT FOR OPHTHALMIC USE. NOT FOR
INJECTION.
CIPRO® HC OTIC should be discontinued at the first
appearance of a skin rash or any other sign of hypersensitivity. Serious and
occasionally fatal hypersensitivity (anaphylactic) reactions, some following the
first dose, have been reported in patients receiving systemic quinolones.
Serious acute hypersensitivity reactions may require immediate emergency
treatment.
PRECAUTIONS
GENERAL
As with other antibiotic preparations, use of this product may
result in overgrowth of nonsusceptible organisms, including fungi. If the
infection is not improved after one week of therapy, cultures should be obtained
to guide further treatment.
Information for PatientsIf rash or allergic reaction occurs, discontinue use immediately
and contact your physician.
Do not use in the eyes.
Avoid contaminating the dropper with material from the ear, fingers, or other
sources.
Protect from light.
Shake well immediately before using.
Discard unused portion after therapy is completed.
Carcinogenesis, Mutagenesis, Impairment of
Fertility
Eight in vitro mutagenicity tests have
been conducted with ciprofloxacin, and the test results are listed below:
Salmonella/Microsome Test (Negative)
E. coli DNA Repair Assay (Negative)
Mouse Lymphoma Cell Forward Mutation Assay (Positive)
Chinese Hamster V79 Cell HGPRT Test (Negative)
Syrian Hamster Embryo Cell Transformation Assay (Negative)
Saccharomyces cerevisiae Point Mutation Assay
(Negative)
Saccharomyces cerevisiae Mitotic Crossover and
Gene Conversion Assay (Negative)
Rat Hepatocyte DNA Repair Assay (Positive)
Thus, 2 of the 8 tests were positive, but results of the following 3 in vivo
test systems gave negative results:
Rat Hepatocyte DNA Repair Assay
Micronucleus Test (Mice)
Dominant Lethal Test (Mice)
Long-term carcinogenicity studies in mice and rats have been completed for
ciprofloxacin. After daily oral doses of 750 mg/kg (mice) and 250 mg/kg (rats)
were administered for up to 2 years, there was no evidence that ciprofloxacin
had any carcinogenic or tumorigenic effects in these species. No long term
studies of CIPRO® HC OTIC suspension have been performed
to evaluate carcinogenic potential.
Fertility studies performed in rats at oral doses of ciprofloxacin up to 100
mg/kg/day revealed no evidence of impairment. This would be over 1000 times the
maximum recommended clinical dose of ototopical ciprofloxacin based upon body
surface area, assuming total absorption of ciprofloxacin from the ear of a
patient treated with CIPRO® HC OTIC twice per day.
Long term studies have not been performed to evaluate the carcinogenic
potential or the effect on fertility of topical hydrocortisone. Mutagenicity
studies with hydrocortisone were negative.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Reproduction studies have been performed in rats and mice using
oral doses of up to 100 mg/kg and IV doses up to 30 mg/kg and have revealed no
evidence of harm to the fetus as a result of ciprofloxacin. In rabbits,
ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances
resulting in maternal weight loss and an increased incidence of abortion, but no
teratogenicity was observed at either dose. After intravenous administration of
doses up to 20 mg/kg, no maternal toxicity was produced in the rabbit, and no
embryotoxicity or teratogenicity was observed.
Corticosteroids are generally teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. The more potent
corticosteroids have been shown to be teratogenic after dermal application in
laboratory animals.
Animal reproduction studies have not been conducted with CIPRO® HC OTIC. No adequate and well controlled studies have been
performed in pregnant women. Caution should be exercised when CIPRO® HC OTIC is used by a pregnant woman.
Nursing Mothers
Ciprofloxacin is excreted in human milk with systemic use. It is
not known whether ciprofloxacin is excreted in human milk following topical otic
administration. Because of the potential for serious adverse reactions 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
The safety and efficacy of CIPRO® HC OTIC
have been established in pediatric patients 2 years and older (131 patients) in
adequate and well-controlled clinical trials. Although no data are available on
patients less than age 2 years, there are no known safety concerns or
differences in the disease process in this population which would preclude use
of this product in patients one year and older. See DOSAGE AND ADMINISTRATION.
