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Producer: Bayer HealthCare Pharmaceuticals (Bayer Helsiker Pharmasyyutikal) Germany
Code of automatic telephone exchange: J01MA02
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active agent: 291 mg of ciprofloxacin of a hydrochloride monohydrate that corresponds to 250 mg of ciprofloxacin of the basis.
Each tablet of 500 mg contains:
Active agent: 582 mg of ciprofloxacin of a hydrochloride monohydrate that corresponds to 500 mg of ciprofloxacin of the basis.
Excipients: starch corn, cellulose microcrystallic, кросповидон, silicon dioxide colloid anhydrous, magnesium stearate, macrogoal 4000, gipromelloza, titanium dioxide.
Description. Tablets of 250 mg: round, biconvex tablets of white or almost white color with slightly yellowish shade, film coated, from risky. On a surface of the tablet containing to risk on one side from risks there is a stamping of "CIP", on other side - "250"; on a surface of the tablet which is not containing to risk there is a stamping in the form of the image of the trademark of firm-izgotovitelya:bayer
Tablets of 500 mg: kapsulovidny, biconvex tablets of white or almost white color with slightly yellowish shade, film coated, from risky. On a surface of the tablet containing to risk on one side from risks there is a stamping of "CIP", on other side - "500"; on a surface of the tablet which is not containing to risk there is a stamping in the form of a text of "BAYER".
Pharmacological properties:
Pharmacodynamics. Ciprofloxacin represents synthetic antibacterial drug of a broad spectrum of activity from group of ftorkhinolon. Action mechanism
Ciprofloxacin has activity of in vitro concerning a wide range of gram-negative and gram-positive microorganisms. Bactericidal effect of ciprofloxacin is carried out by means of inhibition of bacterial topoisomerases II of type (topoisomerase II (DNK-giraza) and topoisomerase IV) which are necessary for replication, a transcription, a reparation and a recombination bacterial
DNA.
Resistance mechanisms
Resistance of in vitro to ciprofloxacin is often caused by dot mutations of bacterial topoisomerases and DNK-girazy and develops slowly by means of multistage mutations.
Single mutations can lead rather to decrease in sensitivity, than to development of clinical stability, however multiple mutations generally lead to development of clinical resistance to ciprofloxacin and to cross resistance to drugs of a hinolonovy row. Resistance to ciprofloxacin, as well as to many other antibiotics, can form as a result of decrease in permeability of a cell wall of bacteria (as it often occurs in case of Pseudomonas aeruginosa) and/or activation of removal from a microbic cell (эффлюкс). It is reported about development of the resistance caused by the coding Qnr gene localized on plasmids. Resistance mechanisms which lead to an inactivation of penicillin of cephalosporins, aminoglycosides, macroleads and tetracyclines probably do not break antibacterial activity of ciprofloxacin. Microorganisms, resistant to these drugs, can be sensitive to ciprofloxacin. The Minimum Bactericidal Concentration (MBC) usually does not exceed the minimum inhibiting concentration (MIC) more than twice.
Testing of sensitivity of in vitro
The reproduced criteria of a research of sensitivity to ciprofloxacin approved by the European committee on definition of sensitivity to antibiotics (EUCAST) are given in the table below:
The European committee on definition of sensitivity to antibiotics. The MIK boundary values (mg/l) in clinical conditions for ciprofloxacin.
Microorganism Sensitive [mg/l] Resistant [mg/l]
Enterobacteriaceae <0,5> 1
Pseudomonas spp. < 0,5> 1
Acinetobacter spp. < 1> 1
Staphylococcus1 spp. < 1> 1
Streptococcus pneumoniae2 <0,125> 2
Haemophilus influenzae and
Moraxella catarrhalis3 <0,5> 0,5
Neisseria gonorrhoeae <0,03> 0,06
Neisseria meningitides <0,03> 0,06
Boundary values,
not connected with types
mikroorganizmov4 <0,5> 1
1. Staphylococcus spp. - boundary values for ciprofloxacin and an ofloksatsin are connected with high-dose therapy.
2. Streptococcus pneumoniae - wild type S. pneumoniae is not considered sensitive to
3. Strains meet the MIK value exceeding a threshold ratio sensitive / умеренно-чувствительные very seldom, and still messages on them were not. Identification tests and antimicrobic sensitivity at detection of such colonies need to be repeated, and results have to be confirmed in the analysis of colonies in referensny laboratory. Until the evidence of the clinical answer for strains with the confirmed MIK values exceeding the resistance threshold which is used now is obtained, they have to be considered as resistant. Haemophilus spp. / Moraxella spp. - identification of strains of Haemophilus influenzae with low sensitivity to ftorkhinolona is possible (MIK for ciprofloxacin - 0,125-0,5 mg/l). Proofs of clinical value of low resistance at the respiratory infections caused by H. Influenzae no.
4. The boundary values which are not connected with species of microorganisms were defined generally on the basis of data of a pharmacokinetics/pharmacodynamics and do not depend on distribution of MIK for specific types. They are applicable only for types for which the sensitivity threshold specific for the sake of appearances, but not for those types for which it is not recommended to hold sensitivity testing was not defined. For certain strains distribution of the acquired resistance can differ depending on the geographical region and eventually. In this regard it is desirable to have local information on resistance, especially at treatment of serious infections.
Data of institute of clinical and laboratory standards for the MIK boundary values (mg/l) and diffusion testing (diameter of a zone [mm]) with use of the disks containing 5 mkg of ciprofloxacin are given in the table below.
Institute of clinical and laboratory standards. Boundary values for MIK (mg/l) and for diffusion testing (mm) with use of disks.
Microorganism Sensitive Intermediate Resistant
Enterobacteriaceae <1a 2a > 4a
> 21b 16-20b <15b
Pseudomonas aeruginosa <1a 2a > 4a
and other bacteria,
not relating to
to family
Enterobacteriaceae
> 21b 16-20b <15b
Staphylococcus spp. <1a 2a > 4a
> 21b 16-20b <15b
Enterococcus spp. <1a 2a > 4a
> 21b 16-20b <15b
Haemophilus spp. <1v - --
> 21 g - --
Neisseria gonorrhoeae <0,06d 0,12-0,5d > 1d
> 41d 28-40d <27d
Neisseria meningitides <0,03e 0,06e > 0,12e
> 35zh 33-34zh <32zh
Bacillus anthracis
Yersinia pestis <0,25a - --
Francisella tularensis <0,5z - --
This reproduced standard is applicable only to tests with use of cultivations with broth using the cationic corrected broth of Mueller-Hinton (CAMHB) which incubate with access of air at
. This reproduced standard is applicable only to diffusion tests with use of disks using an agar of Mueller-Hinton which incubate with access of air at a temperature of 35±2 °C during 16-18 h.
century. This reproduced standard is applicable only to diffusion tests with use of disks for definition of sensitivity with Haemophilus influenzae and Haemophilus parainfluenzae using the bouillon test environment for Haemophilus spp. (NTM) which incubate with access of air at a temperature of 35 °C ± 2 °C during 20-24 h.
. This reproduced standard is applicable only to diffusion tests with use of disks using NTM which incubate in 5% of CO2 at a temperature of 35 °C ± 2 °C during 16-18 h.
. This reproduced standard is applicable only to tests of sensitivity (diffusion tests with use of disks for zones and agar solution for MIK) using a gonococcal agar and 1% of the established growth additive at a temperature of 36 °C ± 1 °C (not exceeding 37 °C) in 5% of CO2 during 20-24 h.
e. This reproduced standard is applicable only to tests with use of cultivations with broth using cationic corrected Mueller-Hinton's (CAMHB) broth about addition of 5% of blood of sheep which incubate in 5% of CO 2 at 35±2 °C during 20-24 h.
. This reproduced standard is applicable only to tests with use of cultivations with broth using cationic corrected Mueller-Hinton's (CAMHB) broth with addition of the growth additive determined by 2% which incubate with access of air at 35±2 °C during 48 h.
In vitro sensitivity to ciprofloxacin
For certain strains distribution of the acquired resistance can differ depending on the geographical region and eventually. In this regard when testing sensitivity of a strain it is desirable to have local information on resistance, especially at treatment of heavy infections. If local prevalence of resistance such is that the advantage of use of drug, at least, concerning several types of infections, is doubtful, - it is necessary to consult with the specialist.
In vitro was shown activity of ciprofloxacin concerning the following sensitive strains of microorganisms:
Aerobic gram-positive microorganisms: Bacillus anthracis, Staphylococcus aureus (Methicillinum - sensitive), Staphylococcus saprophyticus, Streptococcus spp. Aerobic gram-negative microorganisms: Aeromonas spp., Moraxella catarrhalis, Brucella spp., Neisseria meningitidis, Citrobacter koseri, Pasteurella spp., Francisella tularensi, Salmonella spp., Haemophilus ducreyi, Shigella spp., Haemophilius influenzae, Vibrio spp., Legionella spp., Yersiniapestis.
Anaerobic microorganisms: Mobiluncus spp.
Other mikrooganizm: Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.
The varying sensitivity degree to ciprofloxacin for the following microorganisms was shown: Acinetobacter baumann, Burkholderia cepacia, Campylobacter spp., Citrobacter freundii, Enterococcus faecalis, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia marcescens, Streptococcus pneumoniae, Peptostreptococcus spp., Propionibacterium acnes.
It is considered that natural resistance to ciprofloxacin Staphylococcus aureus have (Methicillinum - resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enteroccus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (except for Mobiluncus spp., Peptostreptococus spp., Propionibacterium acnes).
Pharmacokinetics. Absorption
After oral administration ciprofloxacin is quickly soaked up preferential in a small bowel. The maximum concentration of ciprofloxacin in blood serum is reached in 1-2 h. Bioavailability makes about 70-80%. Values of the maximum concentration (With max) and the areas under a curve "concentration - time" (AUC) increase in a blood plasma in proportion to a dose.
Distribution
Communication of ciprofloxacin with proteins of a blood plasma makes 20-30%; active agent is present at a blood plasma preferential in not ionized form. Ciprofloxacin is freely distributed in fabrics and liquids of an organism. Distribution volume in an organism makes 2-3 l/kg. Concentration of ciprofloxacin in fabrics considerably exceeds concentration in blood serum.
Metabolism
It Biotransformirutsya in a liver. In blood four metabolites of ciprofloxacin in small concentration can be found: diethylciprofloxacin (M1), sulfociprofloxacin (Sq.m), oxociprofloxacin (M3), formylciprofloxacin (M4), three of which (M1-M3) show the antibacterial activity of in vitro comparable to antibacterial activity of Acidum nalidixicum. Antibacterial activity of in vitro of a metabolite of M4 which is present at smaller quantity corresponds to activity of norfloxacin more.
Removal
Ciprofloxacin is removed from an organism preferential by kidneys by glomerular filtering and canalicular secretion; insignificant quantity - through digestive tract. The renal clearance makes 0,18-0,3 l/h/kg, the general clearance - 0,48-0,60 l/h/kg. About 1% of the entered dose is removed with bile. In bile ciprofloxacin is present at high concentration. At patients with not changed function of kidneys the elimination half-life makes usually 3-5 h. At a renal failure the elimination half-life increases.
Indications to use:
The uncomplicated and complicated infections caused by microorganisms, sensitive to ciprofloxacin.
Adults
- respiratory infections. Ciprofloxacin is rekomedutsya to be appointed at nevmoniya, the caused Klebsiella spp., Enterobacter spp., Proteus spp., Esherichia coli, Pseudomonas aeruginosa, Haemophilus spp., Moraxella catarrhalis, Legionella spp. and stafilokokkam,
- infections of a middle ear (average otitis), adnexal bosoms (sinusitis), especially if these infections are caused by gram-negative microorganisms, including Pseudomonas aeruginosa or staphylococcus,
- infections of eyes,
- infections of kidneys and/or urinary tract,
- infections of generative organs, including an adnexitis, gonorrhea, prostatitis,
- infections of an abdominal cavity (bacterial infections of digestive tract, biliary tract, peritonitis),
- infections of skin and soft tissues,
- sepsis,
- infections or prevention of infections at patients with reduced immunity (patients, accepting immunodepressants or patients with a neutropenia),
- the selection decontamination of intestines at patients with reduced immunity,
- prevention and treatment of a pulmonary form of a malignant anthrax (Bacillus anthracis infection),
- prevention of the invasive infections caused by Neisseria meningitidis
It is necessary to take into account the acting official managements about rules of use of antibacterial agents.
Children
- treatment of the complications caused by Pseudomonas aeruginosa in children with a mucoviscidosis of easy from 5 to 17 years;
- prevention and treatment of a pulmonary form of a malignant anthrax (Bacillus anthracis infection).
Route of administration and doses:
Pill should be taken inside, irrespective of meal, without chewing, washing down with a small amount of liquid.
If drug is used on an empty stomach, active substance is soaked up quicker. In this case tablets should not be washed down with the dairy products or drinks enriched with calcium (for example, milk, yogurt, juice with the increased content of calcium). The calcium which is contained in usual food does not influence ciprofloxacin absorption.
If because of weight of a state or for other reasons the patient is deprived of an opportunity to take a pill, he is recommended to carry out parenteral therapy by infusion solution of ciprofloxacin, and after improvement of a state to pass to reception of the tableted drug form.
In the absence of other appointments it is recommended to observe the following mode of dosing:
Adults:
Indications the Single dose for adults taking into account
frequency rates of receptions in days
(ciprofloxacin, mg, oral administration)
Respiratory infections
(depending on weight
infections and conditions of the patient) from 2х500 mg to 2х750 mg
Infections of urinogenital system:
- acute, uncomplicated from 2х250 mg to 2х500 mg
- cystitis at women (to a menopause) 1х500 mg
- complicated from 2х500 mg to 2х750 mg
- adnexitis, prostatitis, orchitis,
epididymite from 2х500 mg to 2х750 mg
Gonorrhea
- extragenital 2х250 mg
- acute, uncomplicated 1х500 mg
Diarrhea of 2х500 mg
Other infections (see the section
"Indications to use") 2х500 mg
Especially heavy, representing
threat of life, including.
- streptococcal pneumonia
- recurrent infections
at a mucoviscidosis of easy 2х750 mg
- infections of bones and joints
- septicaemia
- peritonitis.
In particular in the presence
Pseudomonas spp., Staphylococcus spp.
or Streptococcus spp.
Pulmonary form of a malignant anthrax
(treatment and prevention) 2х500 mg
Prevention of invasive infections,
the caused Neisseria meningitides of 1х500 mg
The dosing mode at patients of advanced age (after 65 years)
Patients of advanced age should appoint lower doses of ciprofloxacin depending on disease severity and an indicator of clearance of creatinine.
Children
In the absence of other appointments it is necessary to adhere to the following mode of dosing:
For treatment of complications of a mucoviscidosis of the lungs caused by Pseudomonas aeruginosa (children have from 5 to 17 years) the recommended dose of ciprofloxacin makes 10 mg/kg of weight intravenously 3 times a day (the maximum dose of 1200 mg). Duration of therapy makes 10-14 days.
The dosing mode at a pulmonary form of a malignant anthrax (treatment and prevention)
• Adults: 500 mg 2 times a day.
• Children: 15 mg/kg of weight 2 times a day. It is not necessary to exceed the maximum single dose of 500 mg and a daily dose - 1000 mg.
Administration of drug should be begun right after the assumed or confirmed infection.
The general duration of reception of ciprofloxacin at a pulmonary form of a malignant anthrax makes 60 days.
The dosing mode at renal failures or a liver at adults
1. Renal failure
1.1. At clearance of creatinine from 30 to 60 ml/min. / 1.73 sq.m or its concentration in a blood plasma from 1,4 to 1,9 mg / 100 ml the maximum dose of ciprofloxacin has to make 1000 mg a day.
1.2. At clearance of creatinine of 30 ml/min. / 1,73 sq.m and less or its concentration in a blood plasma from 2 mg / 100 ml or more, the maximum dose of ciprofloxacin has to make 500 mg a day.
2. Renal failure and hemodialysis
The mode of dosing is similar described in point 1.2. In days of carrying out a hemodialysis ciprofloxacin adopt procedures after implementation.
3. A renal failure and peritoneal dialysis at ambulatory patients
1 tablet on 500 mg of ciprofloxacin (or 2 tablets on 250 mg).
4. Abnormal liver function
Correction of a dose is not required.
5. Renal failure and liver
The mode of dosing is similar described in points 1.1. and 1.2.
The dosing mode at renal failures or a liver at children
The dosing mode at children with disturbances of functions of kidneys and a liver was not studied.
Therapy duration
Duration of treatment depends on disease severity, clinical and bacteriological control. It is important to continue treatment systematically, not less than 3 days after disappearance of fever or other clinical symptoms. Average duration of treatment:
- 1 day at acute uncomplicated gonorrhea and cystitis,
- up to 7 days at infections of kidneys, urinary tract, abdominal organs,
- the entire period of a neutropenia at patients with the weakened immunity,
- no more than 2 months at osteomyelitis,
- from 7 to 14 days at other infections.
At the infections caused by streptococci because of risk of late complications treatment has to continue not less than 10 days.
At the infections caused by chlamydias, it is also necessary to continue treatment not less than 10 days.
Features of use:
The heavy infections, staphylococcal infections and infections caused by gram-positive and anaerobic bacteria
At treatment of the heavy infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in a combination with the appropriate antibacterial agents.
The infections caused by Streptococcus _ pneumoniae
Ciprofloxacin is not recommended to be used for treatment of the infections caused by Streptococcus pneumoniae because of its insufficient efficiency concerning the activator.
Infections of a genital tract
At the genital infections which are presumably caused by Neisseria gonorr^eae strains steady against ftorkhinolona it is necessary to consider local information on resistance to ciprofloxacin and to confirm sensitivity of the activator in laboratory tests.
Disturbances from heart
Ciprofloxacin exerts impact on lengthening of an interval of QT (see the section "Side effect"). At elderly patients hypersensitivity to effect of the drugs causing lengthening of an interval of QT is noted. Therefore it is necessary to use with care ciprofloxacin in a combination with the drugs extending QT interval (for example, antiarrhytmic drugs of classes I A and III), or patients with the increased risk have development of arrhythmia like "pirouette" (for example, with the known prolongation of an interval of QT which is not adjusted by a hypopotassemia).
Use for children
It was established that, ciprofloxacin, as well as other drugs of this class, causes an arthropathy of large joints in animals. In the analysis of the data on safety of use of ciprofloxacin for children existing today up to 18 years, the majority of which have a mucoviscidosis of lungs, connection between injury of a cartilage or joints is not established with administration of drug. It is not recommended to use ciprofloxacin at children for treatment of other diseases, except treatment of complications of a mucoviscidosis of the lungs (at children is from 5 to 17 years) tied with Pseudomonas aeruginosa and for treatment and prevention of a pulmonary form of a malignant anthrax (after the assumed or proved Bacillus anthracis infection).
Hypersensitivity
After reception of the first dose of ciprofloxacin hypersensitivity to drug, including allergic reactions can sometimes develop what it is necessary to report to the attending physician immediately about. In rare instances after the first use there can be anaphylactic reactions up to anafilakticheky shock. In these cases use of ciprofloxacin should be stopped and carried out immediately the corresponding treatment. Digestive tract
At emergence in time or after treatment by ciprofloxacin of heavy and long diarrhea it is necessary to exclude the diagnosis of pseudomembranous colitis which demands immediate drug withdrawal and purpose of the corresponding treatment (Vancomycinum inside in a dose of 250 mg 4 times a day).
Use of the drugs suppressing an intestines peristaltics is contraindicated. At the patients who had a liver disease cholestatic jaundice, and also temporary increase in activity of "hepatic" transaminases and an alkaline phosphatase can be noted.
Musculoskeletal system
At the first signs of a tendinitis (painful hypostasis in a joint, an inflammation) use of ciprofloxacin should be stopped, to exclude exercise stresses since there is a risk of a rupture of a sinew, and also to consult with the doctor.
At the elderly patients with diseases of sinews or who were earlier receiving treatment by glucocorticosteroids cases of a rupture of sinews (preferential Achilles sinew) can be noted.
Ciprofloxacin should be applied with care at the patients having in the anamnesis of the instruction on the diseases of sinews connected with reception of hinolon.
Nervous system
Patients with epilepsy and TsNS which transferred diseases (for example, reduction of the threshold of convulsive readiness, convulsive attacks in the anamnesis, disturbances of cerebral circulation, organic lesions of a brain or a stroke) in connection with threat of development of side reactions from TsNS should apply ciprofloxacin only when the expected clinical effect surpasses possible risk of side effect of drug.
In certain cases side reactions from TsNS can arise after the first use of drug. Seldom or never psychosis can be shown by suicide attempts. In these cases it is necessary to stop immediately reception of ciprofloxacin and to report about it to the doctor.
Integuments
At reception of ciprofloxacin there can be a reaction of a photosensitization therefore patients should avoid contact with direct sunshine and UF-light. Treatment should be stopped if photosensitization symptoms are observed (for example, change of integuments reminds sunblisters).
P450 cytochrome
It is known that ciprofloxacin is moderate inhibitor of isoenzymes of CYP 450 1 A2. It is necessary to be careful at simultaneous use of ciprofloxacin and drugs, metaboliziruyemy these enzymes, such as theophylline, methylxanthine, caffeine, дулоксетин, clozapine, etc. as the increase in concentration of these drugs in blood serum caused by inhibition of their metabolism by ciprofloxacin can cause specific undesirable reactions. In order to avoid development of a crystalluria exceeding of the recommended daily dose is inadmissible, also sufficient consumption of liquid and maintenance of acid reaction of urine is necessary.
In vitro in laboratory tests ciprofloxacin suppresses Mycobacterium spp growth., what can result in false-negative results at diagnosis of this activator at the patients accepting ciprofloxacin.
Influence on ability to drive the car and moving mechanisms
Ftorkhinolona, including ciprofloxacin, can break ability of patients to drive the car and to be engaged in other potentially dangerous types of activity requiring special attention and speed of psychomotor reactions owing to influence on TsNS.
Side effects:
The listed below adverse reactions classified as follows: "it is very frequent" (> 10), is "frequent" (> 1/100, <1/10), "infrequently" (> 1/1000, <1/100), is "rare" (> 1/10 000, <1/1000), "it is very rare" (<10 000), "frequency is unknown".
INFECTIOUS AND PARASITIC DISEASES
Infrequently> 0,1% - <1%
Fungal superinfections
Seldom> 0,01% - <0,1%
Psevdomembranoz ny colitis (seldom or never with possible death)
FROM SYSTEM OF THE HEMOPOIESIS
Infrequently> 0,1% - <1%
Eosinophilia
Seldom> 0,01% - <0,1%
Leukopenia. Anemia. Neutropenia. Leukocytosis. Thrombocytopenia. Trombotsitemiya
Very seldom <0,01%
Hemolitic anemia. Agranulocytosis. Pancytopenia (life-threatening). Oppression of marrow (life-threatening)
FROM IMMUNE SYSTEM
Seldom> 0,01% - <0,1%
Allergic reactions. Allergiichesky hypostasis / Quincke's disease
Very seldom <0,01%
Anaphylactic reactions. Anafilakticheky shock (life-threatening) Serum disease
FROM THE METABOLISM AND FOOD
Infrequently> 0,1% - <1%
Anorexia
Seldom> 0,01% - <0,1%
Hyperglycemia
MENTAL DISORDERS
Infrequently> 0,1% - <1%
Psychomotor hyperactivity / agitation
Seldom> 0,01% - <0,1%
Confusion of consciousness and disorientation. Uneasiness. Sleep disorder. Depression. Dreadful dreams. Hallucinations
Very seldom <0,01%
Psychotic reactions
FROM THE CENTRAL NERVOUS SYSTEM
Infrequently> 0,1% - <1%
Headache. Dizziness. Sleep disorder. Taste disturbance
Seldom> 0,01% - <0,1%
Paresthesias and dizesteziya. Hypesthesias. Tremor. Spasms. Vertigo
Very seldom <0,01%
Migraine. Lack of coordination of movements. Disturbance of sense of smell. Hyperesthesia. Intracranial hypertensia
Frequency is unknown
Peripheral neuropathy and polyneuropathy
FROM THE ORGAN OF SIGHT
Seldom> 0,01% - <0,1%
Visual disturbances
Very seldom <0,01%
Disturbance of color perception
FROM THE ACOUSTIC ORGAN AND LABYRINTH DISTURBANCES
Seldom> 0,01% - <0,1%
Sonitus. Hearing loss
Very seldom <0,01%
Hearing disorder
FROM HEART
Seldom> 0,01% - <0,1%
Tachycardia
Frequency is unknown
Lengthening of an interval of QT Ventricular arrhythmias (including pirouette type) *
FROM VESSELS
Seldom> 0,01% - <0,1%
Vazodilatation Lowering of arterial pressure. Feeling of "inflow" of blood to the person
Very seldom <0,01%
Vasculitis
FROM RESPIRATORY SYSTEM, BODIES OF THE THORAX AND
MEDIASTINUMS
Seldom> 0,01% - <0,1%
Breath disturbance (including a bronchospasm)
FROM DIGESTIVE TRACT
Often> 1% - <10%
Nausea Diarrhea
Seldom> 0,01% - <0,1%
Vomiting. Abdominal pain. Dyspepsia. Meteorism. Pancreatitis
FROM KIDNEYS AND URINARY TRACT
Infrequently> 0,1% - <1%
Renal failure
Seldom> 0,01% - <0,1%
Renal failure. Hamaturia. Crystalluria. Tubulointerstitsialny nephrite
THE GENERAL FRUSTRATION AND DISTURBANCES IN THE INJECTION SITE
Infrequently> 0,1% - <1%
Pain syndrome of a nonspecific etiology. Febricula. Fever
Seldom> 0,01% - <0,1%
Hypostases. Perspiration (hyperhidrosis)
Very seldom <0,01%
gait disturbance
LABORATORY INDICATORS
Infrequently> 0,1% - <1%
Increase in activity of an alkaline phosphatase in blood
Seldom> 0,01% - <0,1%
Change of concentration of a prothrombin. Increase in activity of amylase
* more often at the patients having Children
At children it was often reported about development of arthropathies.
Interaction with other medicines:
Antiarrhytmic drugs of classes I A and III
It is necessary to be careful at simultaneous use of ciprofloxacin with antiarrhytmic drug of a class I A or a class III as ciprofloxacin can render the additive effect with lengthening of an interval of QT (see the section "Special Instructions").
Formation of chelate connections
The concomitant use of the tableted forms of ciprofloxacin and cationic drugs, mineral additives, calciferous, magnesium, aluminum, iron, a sukralfat, antacids, polymeric phosphatic connections (such as sevelamer, lanthanum carbonate) and the drugs with a big buffer capacity (such as tablets of a didanozin) containing magnesium, aluminum or calcium reduces ciprofloxacin absorption. In such cases ciprofloxacin should be accepted or in 1-2 hours prior to, or in 4 hours after reception of these drugs.
This restriction does not belong to the medicines belonging to a class of blockers of H2-histamine receptors.
Meal and dairy products
It is necessary to avoid the simultaneous use of ciprofloxacin and dairy products or drinks enriched with minerals (for example, milk, the yogurt enriched with calcium orange juice) as at the same time absorption of ciprofloxacin can decrease. However the calcium which is a part of other foodstuff significantly does not influence ciprofloxacin absorption.
Omeprazol
At the combined use of ciprofloxacin and drugs containing омепразол insignificant decrease in the maximum concentration of drug in plasma and reduction of the area under a curve "concentration - time" can be noted.
Theophylline
Simultaneous use of ciprofloxacin and the drugs containing theophylline can cause undesirable increase in concentration of theophylline in a blood plasma and respectively, emergence theophylline - the induced by-effects; seldom or never these by-effects can be menacing for the patient's life. If simultaneous use of these two drugs is inevitable, then it is recommended to carry out constant control behind concentration of theophylline in a blood plasma and if it is necessary, - to lower a theophylline dose.
Other derivatives of xanthine
Simultaneous use of ciprofloxacin and caffeine or pentoksifillin (окспентифиллин) can lead to increase in concentration of derivatives of xanthine in blood serum.
Non-steroidal anti-inflammatory drugs
The combination of very high doses of hinolon (DNK-girazy inhibitors) and some non-steroidal anti-inflammatory drugs (excepting acetylsalicylic acid) can provoke spasms.
Cyclosporine
At the simultaneous use of ciprofloxacin and drugs containing cyclosporine short-term passing increase in concentration of creatinine in a blood plasma was observed. In such cases it is necessary to define two times a week concentration of creatinine in blood. Glibenclamidum
In some cases simultaneous use of ciprofloxacin and the drugs containing Glibenclamidum can strengthen effect of glibenclamide (hypoglycemia).
Probenetsid
Probenetsid slows down ciprofloxacin removal speed kidneys. Simultaneous use of the drugs containing пробенецид and ciprofloxacin increases concentration of ciprofloxacin in a blood plasma. Methotrexate
At simultaneous use of ciprofloxacin tubular transport (renal metabolism) of a methotrexate can be slowed down that can be followed by increase in concentration of a methotrexate in a blood plasma. At the same time the probability of by-effects of a methotrexate can increase. In this regard for the patients receiving the combined therapy by a methotrexate and ciprofloxacin careful observation has to be established.
Tizanidin
As a result of clinical trial with participation of healthy volunteers at the simultaneous use of ciprofloxacin and drugs containing тизанидин increase in concentration of a tizanidin in a blood plasma is revealed: increase in the maximum concentration (Ст£1 of X) by 7 times (from 4 to 21 times), increase in an indicator
"the area under a curve of dependence of concentration from time" (AUC) - by 10 times (from 6 to 24 times). Hypotensive and sedative by-effects are connected with increase in concentration of a tizanidin in blood serum. Thus, simultaneous use of ciprofloxacin and the drugs containing тизанидин, contraindicated.
Duloksetin
During conduct of clinical trials it was shown that simultaneous use of a duloksetin and powerful inhibitors of an isoenzyme CYP450 1A2 (such as флувоксамин) can lead to increase in AUC and Cmax of a duloksetin. Despite the absence of clinical data on possible interaction with ciprofloxacin, it is possible to expect probability of similar interaction at simultaneous use of ciprofloxacin and a duloksetin. Ropinirol
Simultaneous use of a ropinirol and ciprofloxacin, moderate inhibitor of an isoenzyme CYP450 1A2, leads to increase With max and AUC of a ropinirol at 60 and 84%, respectively. It is necessary to control side effects of a ropinirol during its combined use with ciprofloxacin and within a short period of time after end of a combination therapy.
Lidocaine
In a research on healthy volunteers it was established that simultaneous use of the drugs containing lidocaine and ciprofloxacin, moderate inhibitor of an isoenzyme CYP450 1A2, leads to decrease in clearance of lidocaine by 22% at its intravenous administration. Despite good tolerance of lidocaine, at simultaneous use with ciprofloxacin strengthening of side effects owing to interaction is possible. Clozapine
At simultaneous use of clozapine and ciprofloxacin in a dose of 250 mg within 7 days increase in serumal concentration of clozapine and N-desmetilklozapina by 29% and 31%, respectively was observed. It is necessary to control a condition of the patient and if necessary to carry out correction of the mode of dosing of clozapine during its combined use with ciprofloxacin and within a short period of time after end of a combination therapy.
Sildenafil
At simultaneous use for healthy volunteers of ciprofloxacin in a dose of 500 mg and a sildenafila in a dose of 50 mg increase With max and AUC of a sildenafil was noted twice. In this regard use of this combination is possible only after ratio assessment advantage / risk.
Antagonists of vitamin K
Joint use of ciprofloxacin and antagonists of vitamin K (for example, warfarin, an atsenokumarol, a fenprokumon, a fluindon) can lead to strengthening of their anticoagulating action. The size of this effect can change depending on the accompanying infections, age and the general condition of the patient therefore it is difficult to estimate influence of ciprofloxacin on increase INR (the international normalized relation). It is necessary to control rather often MNO during combined use of ciprofloxacin and antagonists of vitamin K, and also within a short period of time after end of a combination therapy.
Contraindications:
Hypersensitivity to ciprofloxacin or other drugs from group of ftorkhinolon, and also to excipients (see the section "Structure").
Simultaneous use of ciprofloxacin and tizanidin because of clinically significant side effects (hypotension, drowsiness) connected with increase in concentration of a tizanidin in a blood plasma (see the section "Interactions with Other Medicines").
Use at pregnancy and during breastfeeding
Safety of use of ciprofloxacin for pregnant women is not established. However on the basis of results of researches on animals it is impossible to exclude completely probability of an adverse effect on joint cartilages of newborns, in this regard pregnant women should not appoint ciprofloxacin.
In too time during the researches for animals of teratogenic action (malformation) it was not established.
Ciprofloxacin is emitted in breast milk. Because of potential risk of injury of joint cartilages of newborns, the feeding women should not appoint ciprofloxacin.
Use for children
Ciprofloxacin is not recommended to be applied at children up to 18 years to treatment of other infectious diseases, except treatment of complications of a mucoviscidosis of the lungs (at children is from 5 to 17 years) caused by Pseudomonas aeruginosa and to treatment and prevention of a pulmonary form of a malignant anthrax (after the assumed or proved Bacillus anthracis infection).
Use of ciprofloxacin for children has to be begun only after ratio assessment advantage/risk in connection with possible side effect on joints and sinews.
With care
At diseases of the central nervous system: epilepsy, reduction of the threshold of convulsive readiness (or convulsive attacks in the anamnesis), decrease in a blood-groove in brain vessels, organic lesions of a brain or a stroke; mental diseases (depression, psychosis); the renal failure (which is also accompanied with a liver failure), advanced age.
Overdose:
In case of overdose at oral administration in several cases reversible toxic impact on a parenchyma of kidneys was noted. Therefore in case of overdose, except holding standard actions (a gastric lavage, use of emetic drugs, introduction of a large amount of liquid, creation of acid reaction of urine), it is also recommended to monitor function of kidneys and to accept magnesium - and kaltsiysoderzhashchy antacids which reduce ciprofloxacin absorption. By means of haemo - or peritoneal dialysis only a small amount of ciprofloxacin (less than 10%) is removed.
Storage conditions:
Period of validity of 5 years. Not to use after the term specified on packaging. To store in dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C.
Issue conditions:
According to the recipe
Packaging:
Tablets film coated on 250 mg and 500 mg. On 10 tablets in the blister; on 1 blister together with the application instruction in a cardboard box.
