 |
|
 |
| |
Ethiflox |
|
| |
|
|
| |
DESCRIPTION
|
Ethiflox (Ciprofloxacin HCl) is a synthetic, sterile, multiple dose, antimicrobial
for topical ophthalmic use. Ciprofloxacin is a fluoroquinolone antibacterial
active against a broad spectrum of gram-positive and gram-negative ocular
pathogens.
Ciprofloxacin HCl is monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1
4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline-carboxylic acid. It is a
faint to light yellow crystalline powder with a molecular weight of 385.8.
It is sparingly soluble in water, slightly soluble in acetic acid and
in methanol, very soluble in dehydrated alcohol, practically insoluble
in acetone, in acetonitrile, in ethyl acetate, in hexane, and in methylene
chloride. Its empirical formula is C17H18FN3O3·HCl·H2O.
Ciprofloxacin differs from other quinolones in that it has a fluorine
atom at the 6-position, a piperazine moiety at the 7-position, and a cyclopropyl
ring at the 1-position.
Each mL of Ethiflox Ophthalmic Solution contains: ACTIVE: Ciprofloxacin
HCl 3.5 mg equivalent to 3 mg base. PRESERVATIVE: Benzalkonium Chloride
0.006%. The pH is approximately 4.5 and the osmolality is approximately
300 mOsm. |
| |
ACTIONS/CLINICAL PHARMACOLOGY |
* SYSTEMIC ABSORPTION: A systemic absorption study was performed in
which CILOXAN Ophthalmic Solution was administered in each eye every two
hours while awake for two days followed by every four hours while awake
for an additional 5 days. The maximum reported plasma concentration of
ciprofloxacin was less than 5 ng/mL. The mean concentration was usually
less than 2.5 ng/mL.
* MICROBIOLOGY: Ciprofloxacin has In Vitro activity against a wide range
of gram negative and gram-positive organisms. The bactericidal action
of ciprofloxacin results from interference with the enzyme DNA gyrase
which is needed for the synthesis of bacterial DNA Ciprofloxacin has been
shown to be active against most strains of the following organisms both
in vitro and in clinical infections. |
| |
GRAM-POSITIVE |
| Staphylococcus Aureus (including methicillin-susceptible
and methicillin-resistant strains), Staphylococcus Epidermidis, Streptococcus
Pneumoniae, Streptococcus (Viridans Group) |
| |
GRAM-NEGATIVE |
Haemophilus Influenzae, Pseudomonas Aeruginosa, Serratia
Marcescens, Ciprofloxacin has been shown to be active In Vitro against
most strains of the following organisms, however, The clinical significance
of these data is unknown:
Gram-positive: Enterococcus Faecalis (Many strains are only moderately
susceptible),
Staphylococcus Haemolyticus, Staphylococcus Saprophyticus, Streptococcus
Pyogenes
Gram-negative: Acinetobacter Calcoaceticus Subsp. Anitratus, Aeromonas
Caviae, Aeromonas Hydrophila, Brucella Melitensis, Campylobacter Coli,
Campylobacter jejuni, Citrobacter Diversus, Citrobacter Freundii, Edwardsiella
Tarda, Enterobacter Aerogenes, Enterobacter Cloacae, Escherichia Coli,
Haemophilus Ducreyi, Haemophilus Parainfluenzae, Klebsiella Pneumoniae,
Klebsiella Oxytoca, Legionella Pneumophila, Moraxella (Branhamella) Catarrhalis,
Morganella Morganii, Neisseria Gonorrhoeae, Neisseria Meningitidis, Pasteurella
Multocida, Proteus Mirabilis, Proteus Vulgaris, Providencia Rettgeri,
Providencia Stuartii, Salmonella Enteritidis, Salmonella Typhi, Shigella
Sonneii, Shigella Flexneri, Vibrio Cholerae, Vibrio Parahaemolyticus,
Vibrio Vulnificus, Yersinia Enterocolitica |
| |
OTHER ORGANISMS |
Chlamydia Trachomatis (only moderately susceptible)
and Mycobacterium Tuberculosis (only moderately susceptible). Most strains
of Pseudomonas Cepacia and some strains of Pseudomonas Maltophilia are
resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides
Fragilis and Clostridium Difficile. The minimal bactericidal concentration
(MBC) generally does not exceed the minimal inhibitory concentration (MIC)
by more than a factor of 2. Resistance to ciprofloxacin In Vitro usually
develops slowly (multiple-step mutation).
Ciprofloxacin does not cross-react with other antimicrobial agents such
as beta-lactams or aminoglycosides; therefore, organisms resistant to
these drugs may be susceptible to ciprofloxacin.
* Following therapy with Ciprofloxacin HCl Ophthalmic Solution, 76% of
the patients with corneal ulcers and positive bacterial cultures were
clinically cured and complete re-epithelialization occurred in about 92%
of the ulcers.
* In 3 and 7 day multicenter clinical trials, 52% of the patients with
conjunctivitis and positive conjunctival cultures were clinically cured
and 70-80% had all causative pathogens eradicated by the end of treatment.
|
| |
INDICATIONS AND USAGE |
Ethiflox is indicated for the treatment of infections caused by susceptible
strains of the designated microorganisms in the conditions listed below:
CORNEAL ULCERS:
Pseudomonas Aeruginosa, Serratia Marcescens*, Staphylococcus
Aureus, Staphylococcus Epidermidis, Streptococcus Pneumoniae, Streptococcus
(Viridans Group)*
CONJUNCTIVITIS:
Haemophilus Influenzae, Staphylococcus Aureus,
Staphylococcus Epidermidis, Streptococcus Pneumoniae*
*Efficacy for this organism was studied in fewer than 10 infections. |
| |
CONTRAINDICATIONS |
| A history of hypersensitivity to ciprofloxacin or any other component
of the medication is a contraindication to its use. A history of hypersensitivity
to other quinolones may also contraindicate the use of ciprofloxacin.
|
| |
WARNINGS |
NOT FOR INJECTION INTO THE EYE.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions,
some following the first dose, have been reported in patients receiving
systemic quinolone therapy. Some reactions were accompanied by cardiovascular
collapse, loss of consciousness, tingling, pharyngeal or facial edema,
dyspnea, urticaria, and itching. Only a few patients had a history of
hypersensitivity reactions. Serious anaphylactic reactions require immediate
emergency treatment with epinephrine and other resuscitation measures,
including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids,
pressor amines and airway management, as clinically indicated.
Remove contact lenses before using. |
| |
PRECAUTIONS |
General
As with other antibacterial preparations, prolonged use of ciprofloxacin
may result in overgrowth of nonsusceptible organisms, including fungi.
If superinfection occurs, appropriate therapy should be initiated. Whenever
clinical judgment dictates, the patient should be examined with the aid
of magnification, such as slit lamp biomicroscopy and, where appropriate,
fluorescein staining.
Ciprofloxacin should be discontinued at the first appearance of a skin
rash or any other sign of hypersensitivity reaction.
In clinical studies of patients with bacterial corneal ulcer, a white
crystalline precipitate located in the superficial portion of the corneal
defect was observed in 35 (16.6%) of 210 patients. The onset of the precipitate
was within 24 hours to 7 days after starting therapy. In one patient,
the precipitate was immediately irrigated out upon its appearance. In
17 patients, resolution of the precipitate was seen in 1 to 8 days (seven
within the first 24-72 hours), in five patients, resolution was noted
in 10-13 days. In nine patients, exact resolution days were unavailable;
however, at follow-up examinations, 18-44 days after onset of the event,
complete resolution of the precipitate was noted. In three patients, outcome
information was unavailable. The precipitate did not preclude continued
use of ciprofloxacin, nor did it adversely affect the clinical course
of the ulcer or visual outcome. (SEE ADVERSE REACTIONS).
Information for patients: Do not touch dropper tip to any surface, as
this may contaminate the solution.
DRUG INTERACTIONS:
Specific drug interaction studies have not
been conducted with ophthalmic ciprofloxacin. However, the systemic administration
of some quinolones has been shown to elevate plasma concentrations of
theophylline, interfere with the metabolism of caffeine, enhance the effects
of the oral anticoagulant, warfarin, and its derivatives and have been
associated with transient elevations in serum creatinine in patients receiving
cyclosporine concomitantly.
Crcinogenisis, Mutagenisis, and 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, two of the eight tests were positive, but the results of the following
three 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.
After daily oral dosing for up to two years, there is no evidence that
ciprofloxacin had any carcinogenic or tumorigenic effects in these species.
Pregnancy / Teratogenic Effects
PREGNANCY CATEGORY C: Reproduction studies have been performed in
rats and mice at doses up to six times the usual daily human oral dose
and have revealed no evidence of impaired fertility or harm to the fetus
due to ciprofloxacin. In rabbits, as with most antimicrobial agents, ciprofloxacin
(30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting
in maternal weight loss and an increased incidence of abortion.
No teratogenicity was observed at either dose. After intravenous administration,
at doses up to 20 mg/kg, no maternal toxicity was produced and no embryotoxicity
or teratogenicity was observed. There are no adequate and well controlled
studies in pregnant women. Ethiflox should be used during pregnancy only
if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether topically applied ciprofloxacin is excreted in
human milk; however, it is known that orally administered ciprofloxacin
is excreted in the milk of lactating rats and oral ciprofloxacin has been
reported in human breast milk after a single 500 mg dose. Caution should
be exercised when Ethiflox is administered to a nursing mother.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 1 year
have not been established.
Although ciprofloxacin and other quinolones cause arthropathy in immature
animals after oral administration, topical ocular administration of ciprofloxacin
to immature animals did not cause any arthropathy and there is no evidence
that the ophthalmic dosage form has any effect on the weight-bearing joints.
Drug Interactions
Specific drug interaction studies have not been conducted with ophthalmic
ciprofloxacin. However, the systemic administration of some quinolones
has been shown to elevate plasma concentrations of theophylline, interfere
with the metabolism of caffeine, enhance the effects of the oral anticoagulant,
warfarin, and its derivatives and have been associated with ransient elevations
in serum creatinine in patients receiving cyclosporine concomitantly.
ADVERSE REACTIONS
The most frequently reported drug related adverse reaction was local
burning or discomfort. In corneal ulcer studies with frequent administration
of the drug, white crystalline recipitates were seen in approximately
17% of patients (SEE PRECAUTIONS). Other reactions occurring in less than
10% of patients included lid margin crusting, crystals/scales, foreign
body sensation, itching, conjunctival hyperemia and a bad taste following
instillation. Additional events occurring in less than 1% of patients
included corneal staining, keratopathy/ keratitis, allergic reactions,
lid edema, tearing, photophobia, corneal infiltrates, nausea and decreased
vision.
A topical overdose of Ethiflox may be flushed from the eye(s) with warm
tap water. |
| |
ADVERSE REACTIONS |
The most frequently reported adverse reaction attributed to the use
of cromolyn sodium ophthalmic solution, on the basis of reoccurrence following
readministration, is transient ocular stinging or burning upon instillation.
The following adverse reactions have been reported as infrequent events.
It is unclear whether they are attributable to the drug:
Watery eyes
Itchy eyes
Dryness around the eye
Puffy eyes
Eye irritation
Styes |
| |
DOSAGE AND ADMINISTRATION |
The recommended dosage regimen for the treatment of CORNEAL ULCERS
is: Two drops into the affected eye every 15 minutes for the first six
hours and then two drops into the affected eye every 30 minutes for the
remainder of the first day. On the second day, instill two drops in the
affected eye hourly. On the third through the fourteenth day, place two
drops in the affected eye every four hours. Treatment may be continued
after 14 days if corneal re-epithelialization has not occurred.
The recommended dosage regimen for the treatment of BACTERIAL CONJUNCTIVITIS
is: One or two drops instilled into the conjunctival sac(s) every two
hours while awake for two days and one or two drops every four hours while
awake for the next five days. |
| |
HOW SUPPLIED |
5 mL in plastic dropper bottles.
Store at 2° to 30°C. Protect from light. |
|
|
 |
|
 |
|
|