1
Instruction
for medical application of the preparation of
CIPROFLOXACIN-AKOS
Trade name of the preparation: Ciprofloxacin -AKOS
International nonproprietary name: ciprofloxacin
Dosage form: eye drops
Composition for 1 milliliter:
Active substance: ciprofloxacin hydrochloride (in equivalent of ciprofloxacin) - 3 milligrams;
Accessory substances: benzalkonium chloride, disodium edentate (versene), mannitol
(mannite), sodium acetate trihydrate (sodium acetic 3-aqueous), glacial acetic acid, water for
injections up to 1 ml.
Description: transparent solution of slightly yellowish or slightly siskin-green
color.
Pharmacotherapeutic group: antimicrobial agent, fluoroquinolone.
ATC-code: [S01AX13]
Pharmacological action
Pharmacodynamics
Antimicrobial agent of wide range of actions of the group fluoroquinolones (subgroup
of monofluoroquinolones) for local administration in ophthalmology .
It suppresses bacterial DNA-gyrase (standard sizes II and IV, responsible for the process of supercoiling by chromosomal DNA round nuclear RNA, that is necessary for reading of genetical information), disturbs synthetic process of DNA, growth and fission of bacteria; promotes frank morphological changes (including cell walls and membranes) and
quick death of the bacterial cell.
It acts bacillicidal against gram-negative organisms in the period of rest and fission
(as it influences not only against DNA-gyrase, but also promotes lysis of a cell wall) and it
2
acts bacillicidal against gram-positive microorganisms only in the period fission. It raises
penetrance of a cell envelope of bacteria.
The low toxicity for cells of the macroorganism is accounted for absence of DNAgyrase in them. Against the background of administration of ciprofloxacin the parallel development of tolerance to other antibiotics not belonging to the group of dissociable inhibitors of gyrase does not take place, that makes it high-efficiency with regard to bacteria,
which are resistant, for instance to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.
Sensitive to ciprofloxacin are the following:
gram-negative aerobic bacteria: enterobacteria (Escherichia coli, Salmonella spp.,
Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus
vulgaris, Serratia mareescens, Hafnia alvei, Edwaidsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus
spp., Pseudomonas aeruginosa, Moraxella catarrhalb, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular
causative agents - Legionella pneumophila, Brucella spp., Chlamydia trachomatis, Listeria
monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium
diphtheriae;
gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haeraolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).
The majority of staphylococci, resistant to methicillin are also resistant to ciprofloxacin.
Sensibility of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (situated intracellular) is moderate (for their suppression high concentrations are required).
The following are resistant to the preparation: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia
asteroides. It is not effective in regard to Treponema pallidum.
The resistance to ciprofloxacin develops extremely slowly, because, on the one
3
side, after action of ciprofloxacin practically no persistent microorganisms remain, and on
the other side there are no enzymes in bacterial cells to inactivate it.
The preparation is low-toxic.
Pharmacokinetics
I case of local administration ciprofloxacin well penetrates into tissues of the eyes.
It penetrates into a keratoderma and into an auqeous chamber, especially in damage of
the epithelial cover of the keratoderma. In keratopathy the concentration of ciprofloxacin
in it, is effective against the majority of causative agents of keratic infections.
After a single installation the concentration of ciprofloxacin in moisture of the auqeous chamber is achieved in 10 minutes and amounts 100 µg/ml. Maximum concentration Cmax in moisture of the anterior chamber in 1 hour amounts 190 µg/ml. In 2 hours
the concentration of the preparation begins to decline, at that its antibacterial action in
the keratoderma tissues remains unchanged up to 6 hours, in moisture of the anterior
chamber up to 4 hours.
After instillation the systemic absorption of the preparation is possible. In case of local
administration of the ciprofloxacin eye drops 4 times per 24-hours period in both eyes
within 7 days the average concentration of ciprofloxacin in blood plasma amounts less than
2-2.5 ng/milliliter, maximum concentration is less than 5 ng/milliliter.
In case of local administration the T1/2 out of plasma is 4-5 hours. The preparation is
egested by the kidneys in unaltered form up to 50%, and in the form of metabolites up to
10 %; through an intestinal canal about 15 %. A portion of the preparation is exuded with
human milk.
Indication to application
Infective-inflammatory eye diseases caused by microorganisms sensitive to the preparation:
- acute and subacute conjunctivitis;
- blepharitis, blepharoconjunctivitis;
- keratitis, keratoconjunctivitis;
- anterior uveitis;
- bacterial corneal ulcer;
4
- dacryocystitis;
- meibomitis (sty);
- trachoma;
- infectious eye damages after traumas or penetration of foreign matters.
Preventive measures and treatment of infectious complications in traumas of eyes
and its adnexas (including after removal of foreign matters from the cornea, conjunctiva, after impact of chemical or physical means) and in operations on a ball of the eye
(before- and post-operation infection prophylaxis in ophthalmosurgery).
Contra-indications.
Hyperresponsiveness to ciprofloxacin or to other preparations of the group fluoroquinolones, childhood and adolescence age (up to 18 years), pregnancy, lactation (breast feeding).
With care the preparation should be prescribed to the patients with cerebral atherosclerosis, abnormality of cerebral circulation, convulsive disorder.
Mode of administration and dosages
Topically, by 1-2 drops in a conjunctival sac of the affected eye. The frequency of instillations depends upon severity of the inflammatory process.
In case of easy and moderate severe infection instill 1-2 drops in the conjunctival sac of the
affected eye every 4 hours, in severe infection instill by 2 drops hourly. After the state improvement the dosage and frequency of the instillations should be reduced.
In acute bacterial conjunctivitis, simple, furfuraceous and ulcerosa blepharitis the preparation should be applied 4-8 times per day depending on severity of the inflammatory process, course of treatment is from 5 to 14 days.
In keratitis apply 1 drop at least 6 times per day. In the presence of positive result the duration of the medical maintenance depends upon severity of the keratopathy and usually is 2-4
weeks.
In keratopathy, caused by Pseudomonas aeruginosa the preparation should be allied by 1
drop at least 8-12 times per day. The duration of the medical maintenance depends upon run
of the disease and usually is about 2-3 weeks.
In anterior uveitis the preparation should be prescribed by 1 drop 8-12 times a day. In
5
acute dacryocystitis and canaliculitis the preparation should be prescribed by 1 drop 6-12
times per day, in chronical ones - 4-8 times per day.
In bacterial corneal ulcer: within first 24-hour period the preparation should be applied
every 15 minutes within 6 hours, then by 1 drop every 30 minutes within wakefulness hours;
the second 24-hour period apply by 1 drop within wakefulness hours; from the 3d to 14th day it
should be applied by 1 drop every 4 hours within wakefulness hours. If after the 14 days treatment the epithelialization have not take place, then the treatment can be continued.
For preventive measures of the secondary infection in traumas of an eye and its adnexas it should be applied by 1 drop 4-8 times per day within 1-2 weeks. For preventive
measures of inflammatory diseases after surgical intervention with perforation of the ball of
the eye it should be applied by 1 drop 4-6 times per day within the whole post-operation
period (usually from 5 days to 1 month).
Side effects
Hypersensitivity reaction, itch, burning, slight tenderness and hyperemia conjunctiva,
nausea, rarely - lid hydrops, photophobia, blear-eyedness, sensing of a foreign matter in the
eyes, foul taste in the mouth right after instilling, decrement in visual acuity, occurrence of
white crystalline precipitate in the patients with corneal ulcer, keratitis, keratopathy, feathering or infiltration of the keratoderma, development of superinfection.
Overdosage
The data on overdosage of the preparation is absent.
Interaction with other medicinal preparations
Pharmaceutical interaction: solution of ciprofloxacin is incompatible with solutions of
the medicinal preparations possessing pH value of 3-4, which are physically or chemically
unstable.
In simultaneous combination with other antimicrobial agents synergistic interaction is
usually observed (beta-lactam antibiotics, amino-glycosides, clindamycin, metronidazole).
Special instructions
The solution in the form of eye drops is not designed for intraocular injections!
The preparation should not be administered subconjunctivally or directly in a auqeous
chamber!
6
With the use of other ophthalmological medicinal preparations the interval between
their administration should be at least 5 minutes.
If after application of the drops for a long time the conjunctival hyperemia lasts or
grows then stop the usage of the preparation and consult a doctor.
In the period of the preparation treatment wearing of soft contact lenses is not recommended. With the use of hard lenses remove them before instillation and again put them on
in 15-20 minutes after installation of the preparation.
The patients who after the application temporary lose precision of eyesight should not
operate a car or work with sophisticated techniques, machines or any other sophisticated
equipment requiring precision of eyesight right after instillation of the preparation.
Product form
Eye drops 0.3 %.
The vial for the eye drops contains 5 ml of the eye drops, it has a header dose-meter
and a screwed-down plastic cap. Each vial with the application instructions is put in a cardboard package .
Shell life
2 years. After opening of the vial the keeping time of the preparation is 1 month.
Do not use the preparation after expiry date indicated on the package.
Storage conditions
List B. It should be stored in a place protected from light at temperature from 15 to
25° C. Freezing is not allowed. Keep out of reach of children.
Pharmacy purchasing terms:
Prescription medicine.
Manufacturer/Organization accepting customer complaints:
Open Joint Stock "Kurgan Joint Stock Company of Medical Preparations and Articles
"Sintez" (Sintez JSC)
No. 7, Prospect Konstitutsii, city of Kurgan, Russian Federation, 640008
Tel/fax (3522) 48-16-89
e-mail: real@kurgansintez.ru ,
Web site of the manufacturing company: http://www.kurgansintez.ru