Document
DailyMed Label: Cipro HC
Title
DailyMed Label: Cipro HC
Date
2009
Document type
DailyMed Prescription
Name
Cipro HC
Generic name
ciprofloxacin hydrochloride
Manufacturer
Stat Rx USA
Product information
NDC: 16590-053
Product information
NDC: 16590-053
Description
DESCRIPTION
CIPRO ® HC OTIC (ciprofloxacin
hydrochloride and hydrocortisone otic suspension) contains the synthetic broad
spectrum antibacterial agent, ciprofloxacin hydrochloride, combined with the
anti-inflammatory corticosteroid, hydrocortisone, in a preserved, nonsterile
suspension for otic use. Each mL of CIPRO ® HC OTIC
contains ciprofloxacin hydrochloride (equivalent to 2 mg ciprofloxacin), 10 mg
hydrocortisone, and 9 mg benzyl alcohol as a preservative. The inactive
ingredients are polyvinyl alcohol, sodium chloride, sodium acetate, glacial
acetic acid, phospholipon 90H (modified lecithin), polysorbate, and purified
water. Sodium hydroxide or hydrochloric acid may be added for adjustment of
pH.
Ciprofloxacin, a fluoroquinolone, is available as the monohydrochloride
monohydrate salt of
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic
acid. Its empirical formula is C 17 H 18 FN 3 O 3 •HCI•H 2 O and its chemical structure is
as follows:
Hydrocortisone, pregn-4-ene-3, 20-dione, 11, 17, 21-trihydroxy-(11β)-, is an
anti-inflammatory corticosteroid. Its empirical formula is C 21 H 30 O 5 and its
chemical structure is:
Structure Image 1
Structure Image 2
Indications
INDICATIONS AND USAGE
CIPRO ® HC OTIC is indicated for the
treatment of acute otitis externa in adult and pediatric patients, one year and
older, due to susceptible strains of Pseudomonas aeruginosa, Staphylococcus
aureus, and Proteus mirabilis.
Dosage
DOSAGE AND ADMINISTRATION
SHAKE WELL IMMEDIATELY BEFORE USING.
For children (age 1 year and older) and adults, 3 drops of the suspension
should be instilled into the affected ear twice daily for seven days. The
suspension should be warmed by holding the bottle in the hand for 1-2 minutes to
avoid the dizziness which may result from the instillation of a cold solution
into the ear canal. The patient should lie with the affected ear upward and then
the drops should be instilled. This position should be maintained for 30-60
seconds to facilitate penetration of the drops into the ear. Repeat, if
necessary, for the opposite ear. Discard unused portion after therapy is
completed.
Contraindications
CONTRAINDICATIONS
CIPRO ® HC OTIC is contraindicated in
persons with a history of hypersensitivity to hydrocortisone, ciprofloxacin or
any member of the quinolone class of antimicrobial agents. This nonsterile
product should not be used if the tympanic membrane is perforated. Use of this
product is contraindicated in viral infections of the external canal including
varicella and herpes simplex infections.
Warnings
WARNINGS
NOT 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 Patients
If 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 V 79 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.
Adverse reactions
In Phase 3 clinical trials, a total of 564 patients were treated
with CIPRO
How supplied
HOW SUPPLIED
CIPRO ® HC OTIC is supplied as a white to
off-white opaque suspension in a 10 mL bottle with a dropper dispenser.
NDC 0065-8531-10
Store below 77° F (25° C). Avoid freezing. Protect from light.
U.S. Patent Nos. 4,670,444; 4,844,902; 5,843,930; 5,965,549.
CIPRO is a registered trademark of Bayer AG.
Licensed by Bayer AG
Rx Only
Mfd. by:
ALCON CUSÍ, S.A.
08320 El Masnou - Barcelona
SPAIN
6-13-930
Clinical pharmacology
CLINICAL PHARMACOLOGY
The plasma concentrations of ciprofloxacin were not measured
following three drops of otic suspension administration because the systemic
exposure to ciprofloxacin is expected to be below the limit of quantitation of
the assay (0.05 µg/mL).
Similarly, the predicted Cmax of hydrocortisone is within the range of
endogenous hydrocortisone concentration (0-150 ng/mL), and therefore can not be
differentiated from the endogenous cortisol.
Preclinical studies have shown that CIPRO ® HC OTIC was
not toxic to the guinea pig cochlea when administered intratympanically twice
daily for 30 days and was only weakly irritating to rabbit skin upon repeated
exposure.
Hydrocortisone has been added to aid in the resolution of the inflammatory
response accompanying bacterial infection.
Microbiology Ciprofloxacin has in vitro activity against a wide range of
gram-positive and gram-negative microorganisms. The bactericidal action of
ciprofloxacin results from interference with the enzyme, DNA gyrase, which is
needed for the synthesis of bacterial DNA. Cross-resistance has been observed
between ciprofloxacin and other fluoroquinolones. There is generally no
cross-resistance between ciprofloxacin and other classes of antibacterial agents
such as beta-lactams or aminoglycosides.
Ciprofloxacin has been shown to be active against most strains of the
following microorganisms, both in vitro and in clinical infections of acute
otitis externa as described in the INDICATIONS AND USAGE
section:
Aerobic gram-positive microorganism
Staphylococcus aureus
Aerobic gram-negative microorganisms
Proteus mirabilis
Pseudomonas aeruginosa
Package label
CIPRO HC OTIC SUSP Package Label
Label Image
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1 product
Organization
STAT RX USA LLC