Ciprofloxacin

General characteristics. Structure:

Active ingredient: 250 mg or 500 mg of ciprofloxacin (in the form of a monohydrate hydrochloride) in 1 tablet.

excipients: cellulose microcrystallic, starch corn, povidon-KZO, magnesium stearate.

Cover: film covering (polyvinyl alcohol, titanium dioxide, macrogoal, talc).

Pharmacological properties:

Pharmacodynamics. 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 (topoisomerase II - DNK-giraza and topoisomerase IV) which are necessary for replication, a transcription, a reparation and a recombination of bacterial DNA. Ciprofloxacin affects gram-negative microorganisms during a dormant period and during division as influences not only on DNK-girazu, but also causes a lysis of a cell wall, on gram-positive microorganisms only during division. The hypotoxicity for cells of a macroorganism is explained by absence in them DNK-girazy.

Against the background of reception of ciprofloxacin there is no parallel development of stability to other antibacterial drugs which are not belonging to group of inhibitors of a giraza that does it highly effective in relation to bacteria which are steady, for example, against aminoglycosides, penicillin, cephalosporins, tetracyclines and many other antibacterial drugs.

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, multiple mutations generally lead to development of clinical resistance to ciprofloxacin and to cross resistance to drugs of a hinolonovy row. Resistance to ciprofloxacin can form as a result of decrease in permeability of a cell wall of bacteria and/or activation of removal of ciprofloxacin from a microbic cell. 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.

For certain strains distribution of the acquired resistance can differ depending on the geographical region п eventually.

In vitro sensitivity to ciprofloxacin. 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., Haemophilus influenzae. Vibrio spp., Legionella spp. Yersinia pest is.

Anaerobic microorganisms: Mobiluncus spp.

Other microorganisms: Chlamydia trachomatis, Chlamydia pneumoniae. Mycoplasma luminis. Mycoplasma pneumoniae.

The varying sensitivity degree to ciprofloxacin for the following microorganisms was shown: Acinetobacter baumann, Burkholderia cepacia, Campylobacter spp., Citrobacter freundii. Enterococcus fecal is. Entcrobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia spp. Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratio 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 urealityciun, anaerobic microorganisms (except for Mobiluncus spp. Peptostreptococus spp., Propionibacterium acnes).

Pharmacokinetics. Absorption. After oral administration ciprofloxacin is quickly soaked up from a gastro intestinal path, is preferential in duodenal and a jejunum. The maximum concentration (Smakh) of ciprofloxacin in blood serum is reached in 1-2 h and makes at oral administration 250. 500, 700 and 1000 mg of drug 1,2; 2,4; 4,3 and 5,4 mkg/ml respectively. Bioavailability makes about 70-80%. Values of the maximum concentration under a curve "concentration - time" (AUC) increase in a blood plasma and the area in proportion to a dose. Meal (except for dairy products) slows down absorption, but Smakh and bioavailability does not change.

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 (from 2 to 12 times) exceeds concentration in a blood plasma. High concentration of drug are observed in bile, lungs, kidneys, a liver, a gall bladder, a uterus, semen, prostate gland tissues, almonds, an endometria, fallopian pipes and ovaries. Gets into cerebrospinal fluid in concentration of 6 10% at an uninflammed meninx, 14-37% - at inflamed - from concentration in blood serum. Well gets into intraocular liquid, a bronchial secret, a pleura, a peritoneum, a lymph, breast milk, through a placenta.

Metabolism. It Biotransformirutsya in a liver (15-30%). 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 (50-70%); insignificant quantity - through digestive tract (15-30%). The renal clearance makes 3-5 ml/min., the general clearance about 8-10 ml/min. 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:
• the respiratory infections, pneumonia caused by Klebsiella spp., Enterobacter spp., Proteus spp., Esherichia coli. Pseudomonas aeruginosa, Haemophilus spp., Moraxella catarrhalis, Legionella spp. and stafilokokkam;
• the infections of a middle ear (average otitis), adnexal bosoms (sinusitis) which are especially caused by gram-negative microorganisms including Pseudomonas aeruginosa or staphylococcus;
• infections of eyes;
• infections of urinogenital system (including cystitis, pyelonephritis, an adnexitis, chronic bacterial prostatitis, an orchitis, an epididymite, uncomplicated gonorrhea);
• the complicated intraabdominal infections (in a combination with metronidazole);
• infections of a gall bladder and biliary tract;
• the infections of skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
• infections of bones and joints (osteomyelitis, septic arthritis); sepsis;
• typhoid;
• campilobacteriosis, shigellosis, diarrhea of "travelers";
• infections or prevention of infections at patients with reduced immunity (the 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.

Children:
• therapy 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 (see the section "Interaction with Other Medicines").

The dose of ciprofloxacin depends on disease severity, type of an infection, a condition of an organism, age, weight and a functional condition of kidneys. The recommended dosing mode:

Adults:

- respiratory infections easy and moderate severity - 500 mg 2 times a day, at a heavy current - 750 mg 2 times a day;

- infections of a middle ear (average otitis), adnexal bosoms (sinusitis) - 500 mg 2 times a day;

- infections of urinogenital system: acute, uncomplicated - from 250 mg 2 times a day to 500 mg 2 times a day; cystitis at women (to a menopause): 500 mg of 1 times a day; complicated: from 500 mg 2 times a day to 750 mg 2 times a day;

- gonorrhea - 500 mg of 1 times a day;

- the complicated intraabdominal infections (in a combination with metronidazole) 500 mg 2 times a day;

- the infections of skin and soft tissues (infected ulcers, brines, burns, abscesses, phlegmon) easy and moderate severity - 500 mg 2 times a day, at a heavy current - 750 mg 2 times a day;

- infections of bones and joints (osteomyelitis, septic arthritis) - easy and moderate severity - 500 mg 2 times a day, at a heavy current - 750 mg 2 times a day; a typhoid - 500 mg 2 times a day;

- a campilobacteriosis, a shigellosis, diarrhea of "travelers" - 500 mg 2 times a day;

- at infectious diseases at patients with reduced immunity - on 500 mg 2 times a day (in a combination with other antibiotics);

- prevention and treatment of a pulmonary form of a malignant anthrax - 500 mg 2 times a day; other infections (see the section "Indications") - 500 mg 2 times a day; especially heavy infections posing a threat of life including streptococcal pneumonia, recurrent infections at a mucoviscidosis of lungs, infections of bones and joints, sepsis, a feather drives (in particular in the presence of Pseudomonas spp., Staphylococcus spp. or Streptococcus spp.) - 750 mg 2 times a day;

- prevention of the invasive infections caused by Neisseria meningitidis - weave 500 mg of 1 times in sou.

The dosing mode at patients of advanced age (after 65 years). Patients of advanced age should appoint lower dales of ciprofloxacin depending on disease severity and an indicator of clearance of creatinine.

Children. For treatment of complications, the called Pseudomonas aeruginosa at children with a mucoviscidosis of easy from 5 to 17 years recommended a dale of 20 mg/kg of body weight 2 times a day (maximum a dale of 1500 mg). Duration of therapy makes 10-14 days. Prevention and treatment of a pulmonary form of a malignant anthrax - 15 mg/kg of body weight 2 times a day (maximum one-time a dale of 500 mg. daily - 1000 mg). Administration of drug should be begun right after the assumed or confirmed infection. Duration of reception is 60 days.

The dosing mode at renal failures or a liver at adults. The recommended doses of day of patients with a renal failure:

- 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 daily dose of ciprofloxacin - 1000 mg:

- at clearance of creatinine the ml or more maximum daily dose of ciprofloxacin - 300 mg is lower than 30 ml/min. / 1.73 m2ili of its concentration in a blood plasma from 2 mg / 100;

Patients with a renal failure on a hemodialysis:

- 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 daily dose of ciprofloxacin - 1000 mg;

- 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 maximum daily dose of ciprofloxacin - 500 mg.

In days of carrying out a hemodialysis ciprofloxacin is accepted after the procedure.

The ambulatory patients with a renal failure who are on continuous peritoneal dialysis: maximum sou an exact dose of ciprofloxacin - 500 mg.

Patients with a liver failure. Dose adjustment is not required.

Patients with a renal and liver failure. The mode of dosing is similar to the mode at renal failures.

Children with a renal failure and/or abnormal liver functions. 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 2 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, intraabdominal infections; 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 Streptococcus spp., because of risk of late complications treatment has to continue not less than 10 days; at the infections caused by Chlamydia spp., it is also necessary to continue treatment not less than 10 days.

Features of use:

Pregnancy and lactation. Ciprofloxacin is contraindicated during pregnancy and during breastfeeding.

In case of need uses of ciprofloxacin for mother during breastfeeding, feeding of the child a breast it is necessary to stop prior to treatment.

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.

Tsiprofloksatsip's drug is not choice drug for treatment of the infections caused by Streptococcus pneumoniae because of its limited efficiency concerning the activator.

At the genital infections which are presumably caused by Neisseria gonorrhoecie strains steady against ftorkhinolona it is necessary to consider information on local resistance to ciprofloxacin and to confirm sensitivity excite a tel laboratory tests.

Ciprofloxacin exerts impact on lengthening of an interval of QT (I eat. section "Side effect"). Considering that the big average duration of an interval of QT in comparison е men is characteristic of women, they are more sensitive to the drugs causing lengthening of an interval of QT. At elderly patients hypersensitivity to effect of the drugs causing lengthening of an interval of QT is also noted. It is necessary to apply with care ciprofloxacin in a combination with the drugs extending QT interval (for example, antiarrhytmic drugs of the classes IA and III, tricyclic antidepressants, macroleads, neuroleptics) (see the section "Interaction with Other Medicines"), patients with the increased risk have lengthenings of an interval of QT or development of arrhythmia like "pirouette" (for example, a syndrome of inborn lengthening of an interval of QT. heart diseases (heart failure, a myocardial infarction, bradycardia), an electrolytic imbalance (for example, at a hypopotassemia, a hypomagnesiemia)).

After reception of the first dose of ciprofloxacin hypersensitivity to drug (see the section "Side effect"), 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 an acute anaphylaxis. In these cases drug use ciprofloxacin should be stopped and carried out immediately the corresponding treatment.

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 in this situation contraindicated.

At use of ciprofloxacin cases of a necrosis of a liver and a zhizneugrozhayushchy liver failure, in the presence of symptoms of a disease of a liver, such as anorexia were noted, jaundice, urine darkening, an itch, morbidity of a stomach, use of ciprofloxacin it is necessary to stop.

At the patients who are accepting drug ciprofloxacin and had a liver disease temporary increase in activity of "hepatic" transaminases and an alkaline phosphatase or cholestatic jaundice can be observed.

Patients with a heavy myasthenia of gravis should apply ciprofloxacin with care as the aggravation of symptoms is possible.

At use of ciprofloxacin cases of a tendinitis and a rupture of sinews (preferential Achilles sinew) sometimes bilateral, within the first 48 hours after the beginning of therapy can be noted. An inflammation п a rupture of a sinew can arise even in several months after the treatment termination by ciprofloxacin. Elderly patients and at patients with diseases of the sinews which are at the same time receiving treatment by glucocorticosteroids have an increased risk of emergence of a tendinopatiya. At use of ciprofloxacin it was reported about cases of development of the epileptic status. Ciprofloxacin, as well as other ftorkhinolona, can provoke spasms and reduce a threshold of convulsive readiness, when developing spasms use of drug should be stopped. Mental reactions can arise even after the first use of ftorkhinolon, including ciprofloxacin, in rare instances the depression or psychotic reactions can progress in suicide thoughts and the self-damaging behavior, such as the attempts of a suicide including which came true if at the patient one of these reactions develops, it is necessary to stop administration of drug and to report about it to the doctor. To 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, it is only necessary to apply ciprofloxacin when the expected clinical effect surpasses possible risk of development of side effect of drug.

At reception of ftorkhinolon cases of touch or sensomotor polyneuropathy, hypesthesia, a dizesteziya, weakness were noted. At emergence of such symptoms as pain, burning, a pricking, numbness, weakness, it is necessary not to continue use of drug before consultation with the doctor.

As at administration of drug there can be a reaction of a photosensitization, patients should avoid contact with direct sunshine and ultra-violet light. In case of symptoms of a photosensitization treatment should be stopped.

It is necessary to be careful at simultaneous use of ciprofloxacin and drugs, metaboliziruyemy CYP450 1A2 isoenzymes (such as theophylline, methylxanthine, caffeine, дулоксетин, clozapine, ропинирол, olanzapine).

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 the conditions of in vitro ciprofloxacin can disturb the bacteriological research Mycobacterium tuberculosis, suppressing се growth that can result in false-negative results at diagnosis of this activator at the patients accepting drug.

Prolonged and repeated use of ciprofloxacin can lead to superinfection resistant bacteria or causative agents of fungal infections.

Children. On the basis of the analysis of data on safety of use of ciprofloxacin for children up to 18 years, despite the lack of the proved communication between injury of a cartilage or joints and 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 5-17 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).

Influence on ability to manage vehicles and mechanisms. 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. It is necessary to take potentiality of development of such side effects into account as dizziness, вертиго, confusion of consciousness and drowsiness. At emergence of the described undesirable phenomena it is necessary to refrain from performance of the specified types of activity.

Side effects:

The listed below adverse reactions classified as follows: "very often" (≥ 10), is "frequent" (≥1/100, <1/10). "infrequently" (≥ 1/1000, <1/100), is "rare" (≥ 1/10 000, <1/1000), is "very rare" (<10 000), "frequency is unknown".

From digestive tract: often - nausea, diarrhea; infrequently - vomiting, an abdominal pain, dyspepsia, a meteorism, a loss of appetite and quantities accepted write, anorexia; seldom - a dysphagy, cholestatic jaundice (especially at patients е the postponed liver diseases), hepatitis (noninfectious), oral cavity candidiasis; very seldom - pancreatitis, an antibiotic - the associated pseudomembranous colitis, a necrosis of tissues of liver (in extremely exceptional cases progressing to a life-threatening liver failure).

From system of a hemopoiesis: infrequently - an eosinophilia, it is rare - a leukopenia (granulocytopenia). anemia, a neutropenia, a leukocytosis, thrombocytopenia, it is very rare - hemolitic anemia, an agranulocytosis, a pancytopenia {life-threatening), oppression of marrow (life-threatening).

Allergic reactions: infrequently - skin rash; itch. urticaria, spotty and nodular rash; seldom - allergic reactions, allergic hypostasis / a Quincke's disease, photosensitivity, a multiformny erythema, a knotty erythema; very seldom - anaphylactic reactions, an acute anaphylaxis (life-threatening), a serum disease, Stephens's syndrome - Johnson, a Lyell's disease, dot hemorrhages of a pas to skin, frequency is unknown - an acute generalized pustular dieback.

From a neutral nervous system: infrequently - a headache, dizziness, increased fatigue, a sleep disorder, concern, a psychomotor hyperactivity / agitation, taste disturbance; seldom - paresthesias and dizesteziya, hypesthesias, a tremor, spasms, epilepsy attacks, вертиго, confusion of consciousness, uneasiness; very seldom - migraine, an incoordination of movements, disturbance of sense of smell, a hyperesthesia, benign intracranial hypertensia, disturbance of dreams (nightmares), psychotic reactions (which can result in the self-damaging behavior, such as suicide acts / think, and also attempt of a suicide or the successful suicide), a depression (which can result in the self-damaging behavior, such as suicide acts / think, and also attempt of a suicide or the successful suicide), hallucinations; frequency is unknown - peripheral neuropathy and polyneuropathy.

From an organ of sight: very seldom - visual disturbances, a diplopia, disturbance of color perception.

From an acoustic organ: very seldom - a sonitus, a temporary hearing loss, infrequently - a heart consciousness; seldom - tachycardia, feeling of "inflow" of blood to the person, a vazodilatation, a faint, a lowering of arterial pressure; very seldom - a vasculitis; frequency is unknown - lengthening of an interval of QT, ventricular arrhythmias (including the pirouette type, is more often at the patients having predisposition to development of lengthening of an interval of QT).

From respiratory system: seldom - диспноэ, throat hypostasis, lung hypostasis, breath disturbance (including a bronchospasm).

From skeletal and muscular system: infrequently - an arthralgia; seldom - a mialgiya. joint hypostasis; very seldom - arthritis, increase in a muscle tone, muscular spasms, muscular weakness, a tendinitis (preferential Achilles tendons), a rupture of sinews, an aggravation of symptoms of a myasthenia.

From an urinary system: seldom - an acute renal failure, a hamaturia, a crystalluria, intersticial nephrite.

Others: infrequently - a febricula, fever, fungal superinfection; seldom - a pain syndrome of a nonspecific etiology, peripheral hypostases, perspiration (hyperhidrosis); very seldom - gait disturbance.

Laboratory indicators: infrequently - increase in activity of an alkaline phosphatase in blood, concentration of urea in blood, activities of alaninaminotranspherase (ALT) and aspartate aminotransferase (ACT), a hyperbilirubinemia; seldom - increase or decrease in an indicator of a prothrombin, increase in activity of amylase, a hyperglycemia, a hypoglycemia; frequency is unknown - increase in the international normalized relation (INR) (at the patients receiving antagonists of vitamin K).

Children: often - reversible arthropathies.

Interaction with other medicines:

The drugs causing lengthening of an interval of QT. It is necessary to be careful at simultaneous use of ciprofloxacin (as well as other ftorkhinolon) to the patients receiving the medicines causing lengthening of an interval of QT (for example, antiarrhytmic drugs of the class IA and III, tricyclic antidepressants, macroleads, neuroleptics, see the section "Special Instructions").

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 adverse phenomena: seldom or never these adverse phenomena 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 of concentration of theophylline in a blood plasma and if it is necessary, to lower a theophylline dose (see the section "Special Instructions", P450 cytochrome).

Other derivatives of xanthine. Simultaneous use of a tsiprofloksatsip and caffeine or a pentoksifillin (окспентифиллин) can lead to increase in concentration of derivatives of xanthine in blood serum.

Tizanidin. At the simultaneous use of a tsiprofloksatsip and drugs containing тизанидин increase in concentration of a tizanidin in blood serum is revealed: increase in the maximum concentration (Smakh) in 7 (from 4 to 21) times, increase in an indicator of AUC (the area under a pharmacokinetic curve "concentration time") on average in 10 (from 6 to 24) times. As increase in concentration of a tizanidin in blood serum can cause clinically significant side effects: a lowering of arterial pressure and drowsiness, simultaneous use of a tsiprofloksatsip and the drugs containing тизанидин, contraindicated.

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 cases of combined use of ciprofloxacin and cyclosporine it is necessary to define two times a week concentration of creatinine in blood.

Peroral hypoglycemic means (Glibenclamidum, глимепирид) and insulin. At simultaneous use of ciprofloxacin and peroral hypoglycemic means, mainly, of sulphonylurea drugs, or insulin development of a hypoglycemia is presumably caused by strengthening of action of hypoglycemic means (see the section "Side effect"). Careful monitoring of level of glucose in blood is necessary.

Probenetsid. Probenetsid slows down ciprofloxacin removal speed kidneys. Simultaneous use of ciprofloxacin and the drugs containing пробеницид leads to increase in concentration of ciprofloxacin in a blood plasma.

Phenytoinum. At simultaneous use of ciprofloxacin and Phenytoinum change (increase or decrease) of the maintenance of Phenytoinum in a blood plasma was observed. In order to avoid easing of anticonvulsant effect of Phenytoinum owing to decrease in its concentration, and also for prevention of the undesirable phenomena connected with overdose by Phenytoinum at the ciprofloxacin reception termination also short time after end of a combination therapy is recommended to exercise control of therapy by Phenytoinum at patients, including determination of content of Phenytoinum in a blood plasma during the entire period of simultaneous use of both drugs.

Methotrexate. At simultaneous use of a methotrexate and ciprofloxacin renal and canalicular transport of a methotrexate can be slowed down that can be followed by increase in concentration of a methotrexate in a blood plasma and probability of development of side effects of a methotrexate. In this regard for the patients receiving simultaneous therapy by a methotrexate and ciprofloxacin careful observation has to be established.

Omeprazol. At the combined use of ciprofloxacin and drugs containing омепразол insignificant decrease in the maximum concentration of ciprofloxacin in plasma and reduction of the area under a pharmacokinetic curve "concentration time" can be noted.

Duloksetin. Simultaneous use of a duloksetin and fluvoksamin - powerful inhibitor of an isoenzyme CYP450 1A2, can lead to increase in AUC and Smakh a duloksetin. 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, Smakh and AUC of a ropinirol for 60 and 84%, respectively leads to increase. It is necessary to control adverse effects of a ropinirol during its combined use with ciprofloxacin and within a short period of time after end of a combination therapy.

Lidocaine. Simultaneous use of the drugs containing lidocaine and ciprofloxacin, moderate inhibitor of an isoenzyme CYP450 1A2, can lead to decrease in clearance of lidocaine by 22% at its intravenous administration. At simultaneous use with ciprofloxacin strengthening of side effects owing to interaction is possible (see the section "Special Instructions", P450 cytochrome).

Clozapine. At simultaneous use of clozapine and ciprofloxacin can increase serumal concentration of clozapine and N-desmetilklozapina. 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 (see the section "Special Instructions", P450 cytochrome).

Sildenafil. At simultaneous use of ciprofloxacin and a sildenafil increase Smakh is possible and AUC sildenafit twice. In this regard use of this combination is possible only after ratio assessment advantage/risk.

Antagonists of vitamin K (warfarin, atsenokumarol, фенпрокумон, флуиндон). Combined use of ciprofloxacin and antagonists of vitamin K 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. It is necessary to control 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.

Cationic drugs. Concomitant use of ciprofloxacin and cationic drugs; mineral additives, calciferous, magnesium, aluminum, iron; the sukralfata, antacids, polymeric phosphatic connections (for example, a sevelamer, lanthanum carbonate) and the drugs with a big buffer capacity (for example, 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 э it is silent drugs.

Meal and dairy products. It is necessary to avoid the simultaneous use of ciprofloxacin and dairy products or drinks enriched with minerals (for example, the milk, yogurt enriched with calcium juice) as at the same time absorption of ciprofloxacin can decrease. The calcium which is contained in usual food significantly does not influence ciprofloxacin absorption.

Contraindications:

• hypersensitivity to ciprofloxacin or other drugs from group of ftorkhinolon, and also to other components of drug;
• a concomitant use of ciprofloxacin and a tizanidin (see the section "Interaction with Other Medicines");
• children's age up to 18 years (before completion of process of formation of a skeleton, except the indications specified in the section "Indications to Use", children);
• pregnancy;
• breastfeeding period.

With care. The expressed atherosclerosis of vessels of a brain, disturbance of cerebral circulation, organic lesions of a brain or stroke, mental diseases (depression, psychosis), epilepsy, reduction of the threshold of convulsive readiness (a spasm pla in the anamnesis), the expressed renal and/or liver failure, advanced age, damage of sinews at earlier carried out treatment of a hinolonama, the increased risk of lengthening of an interval of QT or development of arrhythmia like "pirouette" (for example, a syndrome of inborn lengthening of an interval of QT, a heart disease (heart failure, a myocardial infarction, bradycardia), an electrolytic imbalance (for example, at a hypopotassemia, a hypomagnesiemia), simultaneous use of the medicines extending QT interval (including, antiarrhytmic IA and the III classes, tricyclic antidepressants, macroleads, neuroleptics), simultaneous use with inhibitors of isoenzymes CYP450 1A2 (including, theophylline. methylxanthine, caffeine, дулоксетин, clozapine, ропинирол, olanzapine), mental diseases, gravis myasthenia, deficit glyukozo-6-fosfatdegidrogsnazy.

Overdose:

Symptoms: dizziness, a tremor, a headache, fatigue, convulsive attacks, hallucinations, lengthening of an interval of QT, disturbance from the digestive tract (DT), an abnormal liver function and kidneys, a crystalluria, a hamaturia.

Treatment: the specific antidote is unknown. A gastric lavage, reception of absorbent carbon, antacids, calciferous and magnesium for decrease in absorption of ciprofloxacin. For the purpose of prevention of development of a crystalluria it is recommended to monitorirovat function of kidneys, including pH and acidity of urine. Symptomatic therapy. Careful control of a condition of the patient, ensuring sufficient intake of liquid. By means of haemo - or peritoneal dialysis the amount of drug can be removed only insignificant (less than 10%).

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 250 mg, 500 mg. Packaging: on 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. On 10 tablets in bank of polymeric. On 1 blister strip packaging or 1 bank polymeric together with the application instruction in a cardboard pack or in a pack from a cardboard coated.