Ciprofloxacin - instructions for use, dose, side effects, contraindications

Ciprofloxacin has activity in vitro for a wide range of gram-negative and gram-positive bacteria. The mechanism of bactericidal action is associated with the inhibition of the enzyme DNA-gyrase of bacteria (topoisomerases II and IV types, necessary for reading genetic information), as a result of which the synthesis (or replication) of DNA and the synthesis of bacterial cell proteins, the growth and division of bacteria, the pronounced morphological changes and as a result, the death of a bacterial cell occurs. Ciprofloxacin acts bactericidal against gram-negative bacteria both in the fission phase and in those in the resting phase: Gram-positive bacteria only in the fission phase.

Mechanisms of resistance

Resistance in vitro to ciprofloxacin is often caused by point mutations of bacterial topoisomerase and develops slowly through multistage mutations. Single mutations lead to a decrease in sensitivity, rather than to the development of clinical stability. Multiple mutations lead to the development of clinical resistance not only to ciprofloxacin. but also other preparations of the quinolone series. Also, resistance to ciprofloxacin may also be formed as a result of reduced permeability of the bacterial cell wall and / or activation of excretion from the microbial cell (efflux). The development of resistance due to plasmid-localized genes has been reported Qnr.

Resistance mechanisms that lead to the inactivation of penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines probably do not interfere with the antibacterial activity of ciprofloxacin. Microorganisms resistant to these drugs may be sensitive to ciprofloxacin.The minimum bactericidal concentration (MBC) usually does not exceed the minimum inhibitory concentration (MIC) by more than 2 times.

Sensitivity testing in vitro

Reproducible criteria for the study of sensitivity to ciprofloxacin. approved by the European Committee for the Determination of Sensitivity to Antibiotics (EUCAST) are presented in the table below.

European Committee on the definition of sensitivity to antibiotics. Boundary MIC (mg / L) values in clinical settings 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 associated with microbial species⁴	<0,5	>1

¹ Staphylococcus spp. - the borderline values for ciprofloxacin are associated with high-dosage therapy.

² Streptococcus pneumoniae - wild type S. pneumoniae is not considered sensitive to ciprofloxacin and. thus, belongs to the category of microorganisms with intermediate sensitivity.

³ Strains with a MIC value greater than the threshold sensitivity / moderately sensitive thresholds are very rare, and so far there have been no reports of them.Tests for identification and antimicrobial sensitivity in the detection of such colonies must be repeated, and the results should be confirmed when analyzing the colonies in the reference laboratory. Until the evidence of a clinical response is obtained for strains with confirmed MIC values exceeding the current resistance threshold, they should be considered as resistant.

Haemophilus spp. /Moraxella spp. - it is possible to identify strains Haemophilus influenzae with a low sensitivity to fluoroquinolones (MIC for ciprofloxacin - 0.125-0.5 mg / l). Evidence of the clinical significance of low resistance in respiratory tract infections caused by Haemophilus influenzae, no.

⁴ Boundary values not associated with microbial species were determined on the basis of pharmacokinetics / pharmacodynamics data and do not depend on MIC distribution for specific species. They are applicable only to species for which a sensitivity threshold specific to the species has not been determined, and not for those for which testing of sensitivity is not recommended. For certain strains, the spread of acquired resistance may vary depending on the geographical region and over time.In this regard, it is desirable to have local information on resistance, especially when treating serious infections.

Data from the Institute of Clinical and Laboratory Standards for MIC boundary values (mg / L) and diffusion testing (zone diameter, mm) using discs containing 5 μg of ciprofloxacin. are presented in the table below.

Institute of Clinical and Laboratory Standards. Boundary values of MIC (mg / L) diffusion testing (mm) using discs.

Microorganism	Sensitive	Intermediate	Resistant
Enterobacteriaceae	<1^a	2^a	>4^a
	>21^b	16-20^b	<15^a
	<1^a	2^a	>4^a
Pseudomonas aeruginosa and other bacteria belonging to the family Enterobacteriaceae	>21^b	16-20^b	<15^b
Staphylococcus spp.	<l^a	2^a	>4^a
Staphylococcus spp.	>21^b	16-20^b	<15^b
Enterococcus spp.	<l^a	2^a	>4^a
Enterococcus spp.	>21^b	16-20^b	<15^b
Haemophilus spp.	<1^at	-	-
Haemophilus spp.	>2^g	-	-
Neisseria gonorrhoeae	<0,06^d	0,12-0,5^d	>1^d
Neisseria gonorrhoeae	>41^d	28-40^d	<27^d
Neisseria meningitides	<0,03^e	0,06^e	>0,12^e
Neisseria meningitides	>35^f	33-34^f	<32^f
Bacillus anthracis Yersinia pestis	<0,25^a
Francisella tularensis	<0,5	-	-

^a this reproducible standard is applicable only to dilution tests with broth using cullon-adjusted Mueller-Hinton broth (SAMS). which is incubated with air access at a temperature of 35 ± 2 ° C for 16-20 h for strains Enterobacteriaceae, Pseudomonas aeruginosa, other non-family bacteria Enterobacteriaceae, Staphylococcus spp., Enterococcus spp., and Bacillus anthracis; 20-24 hours for Acinetobacter spp., 24 h for Y. Pestis (with insufficient growth, incubate for another 24 hours).

^b this reproducible standard is applicable only to diffusion tests using Müller-Hinton agar plates that are incubated with air access at a temperature of 35 ± 2 ° C for 16-18 hours.

^at This reproducible standard is applicable only to diffusion tests using discs to determine sensitivity with Haemophilus influenzae and Haemophilus parainfluenzae using a broth test medium for Haemophilus spp. (NTM), which is inhibited with air access at a temperature of 35 ± 2 ° C for 20-24 hours.

^g this reproducible standard is applicable only to diffusion tests using discs using NTM. which is incubated in 5% CO₂ at a temperature of 35 ± 2 ° C for 16-18 hours.

^d this reproducible standard is applicable only to sensitivity tests (diffusion tests using zone discs and agar agar for MIC) using gonococcal agar and 1% of the growth additive at 36 ± 1 ° C (not exceeding 37 ° C) in 5% CO₂ for 20-24 hours.

^e this reproducible standard is applicable only to dilutions with broth using cullon-adjusted Mueller-Hinton broth (SAMS) with the addition of 5% sheep blood which is incubated in 5% CO₂ at 35 ± 2 ° C for 20-24 hours.

^f this reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (SAMS) supplemented with a defined 2% growth additive which is incubated with air access at 35 ± 2 ° C for 48 hours.

In vitro sensitivity to ciprofloxacin

The spread of acquired resistance may vary depending on the geographical region and over time. When testing the sensitivity of individual strains, it is desirable to have local information on resistance, especially when treating serious infections. If the local prevalence of resistance is such that the use of the drug, at least for several types of infections, is questionable, then it is necessary to consult a specialist.

In vitro the activity of ciprofloxacin in relation to the following sensitive strains of microorganisms was demonstrated:

Aerobic Gram-positive microorganisms: Bacillus anthracis, Staphylococcus aureus (methicillin-sensitive), Staphylococcus saprophyticus, Streptococcus spp.

Aerobic Gram-negative microorganisms: Aeromonas spp., Moraxella catarrhalis, Brucella spp., Neisseria meningitidis, Citrobacter koseri, Pasternella spp., Francisella tularensis, Salmonella spp., Haemophilus ducreyi, Shigella spp., Haemophilus influenzae, Vibrio spp., Legionella spp,. Yersinia pestis.

Anaerobic microorganisms: Mobiluncus spp.

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

Was demonstrated varying power sensitivity to ciprofloxacin for the following microorganisms: Acinetobacter baumannii, Burkholderia cepacia, Campylobacter spp., Citrobacter freundii, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas fluorescens, Pseudomonas aeruginosa, Serratia marcescens, Streptococcus pneumoniae, Peptostreptococcus spp., Propionibacterium acnes, Enterobacter aerogenes, Enterobacter cloacae.

It is considered, what natural resistance to ciprofloxacin have the Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enterococcus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealyticum, anaerobic microorganisms (with the exception of Mobiluncus spp., Peptostreptococcus spp., Propionibacterium acnes.

Pharmacokinetics:

Suction

After intravenous (IV) infusion, the maximum concentration (FROM_max) ciprofloxacin in blood plasma is achieved at the end of the infusion. With intravenous administration, the pharmacokinetics of ciprofloxacin was linear in the dosage range up to 400 mg. With intravenous administration of the drug 2 or 3 times a day, no cumulation of ciprofloxacin and its metabolites.

Distribution

The relationship of ciprofloxacin with plasma proteins is 20-30%. The active substance is present in the blood plasma mainly in non-ionized form. Ciprofloxacin freely distributed in tissues and body fluids. The volume of distribution in the body is 2-3 l / kg. The concentration of ciprofloxacin in tissues is much higher than the concentration in serum.

Metabolism

Biotransformatsya in the liver. In the blood can be found four metabolites of ciprofloxacin in small concentrations: diethylciprofloxacin (M1), sulfosiprofloxacin (M2), oxocycrofloxacin (M3), formylcycloploxacin (M4), three of which (M1-M3) show antibacterial activity in vitro, comparable with antibacterial activity nalidixic acid. Antibacterial activity in vitro metabolite M4, present in a smaller amount, more corresponds to the activity of norfloxacin.

Excretion

Ciprofloxacin is excreted from the body mainly by the kidneys through glomerular filtration and tubular secretion; a small amount - through the gastrointestinal tract. Kidney clearance is 0.18-0.30 l / h / kg, the total ground clearance is 0.48-0.60 l / h / kg. Approximately 1% of the administered dose is excreted with bile. In the bile ciprofloxacin is present in high concentrations. In patients with unchanged kidney function, the elimination half-life is usually 3-5 hours. If the kidney function is impaired, the elimination half-life increases.

Children

In a study in children, the value of C_max and the area under the "concentration-time" curve (AUC) did not depend on age. A marked increase in C_max and AUC with repeated use of the drug (at a dose of 10 mg / kg 3 times a day) was not observed. In ten children with severe sepsis less than 1 year of age, the value of C_max was 6.1 mg / L (range from 4.6 to 8.3 mg / L) after infusion for 1 hour at a dose of 10 mg / kg, and in children aged 1 to 5 years, 7.2 mg / L (range from 4.7 to 11.8 mg / l). The values of AUC in the corresponding age groups were 17.4 mg * h / l (range 11.8 to 32.0 mg * h / l) and 16.5 mg * h / l (range 11.0 to 23.8 mg * h / l). These values correspond to the range reported to adult patients when therapeutic doses are administered. Based on pharmacokinetic analysis in children with various infections, the estimated average half-life is approximately 4-5 hours.

Indications:

Uncomplicated and complicated infectious-inflammatory diseases caused by microorganisms susceptible to ciprofloxacin:

Adults

- respiratory tract infections. Ciprofloxacin It is recommended to prescribe for pneumonia caused by Klebsiella spp., Enterobacter spp., Proteus spp., Escherichia coli, Pseudomonas aeruginosa, Haemophilus spp., Moraxella catarrhal is, Legionella spp. and Staphylococcus spp.;

- infections of the middle ear (otitis media), adnexal sinuses (sinusitis), especially if these infections are caused by gram-negative bacteria, including Pseudomonas aeruginosa and Staphylococcus spp.;

- eye infections;

- kidney and / or urinary tract infections;

- infection of the genitals (gonorrhea, prostatitis, adnexitis);

- infection of the abdominal cavity (bacterial infections of the gastrointestinal tract, bile ducts, peritonitis):

- infections of the skin and soft tissues;

- sepsis;

- infection or prevention of infections in patients with reduced immunity (patients taking immunosuppressants or patients with neutropenia;

- selective decontamination of the intestine in patients with reduced immunity;

- prevention and treatment of pulmonary form of anthrax (infection Bacillus anthracis).

It is necessary to take into account the current official guidelines on the rules for the use of antibacterial agents.

Children

- treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years:

- prevention and treatment of pulmonary form of anthrax (infection Bacillus anthracis).

Contraindications:

Hypersensitivity to ciprofloxacin or other preparations of the fluoroquinolones group and to auxiliary substances.

Simultaneous administration with tizanidine due to clinically significant side effects (risk of pronounced decrease in blood pressure, drowsiness) associated with an increase in the concentration of tizanidine in the blood plasma (see section "Interaction with other drugs").

Children under 18 years of age (except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years: prevention and treatment of pulmonary form of anthrax).

Pregnancy, lactation.

Carefully:

Pronounced renal and / or hepatic insufficiency; myasthenia gravis gravis; elderly age; deficiency of glucose-6-phosphate dehydrogenase; epilepsy (including in the anamnesis), lowering the threshold of convulsive readiness (or convulsive fits in the anamnesis); severe atherosclerosis of cerebral vessels, cerebral circulatory disorders, organic brain lesions or stroke; mental illness (depression, psychosis); the defeat of the tendons during the previous treatment with quinolones; increased risk of lengthening the interval QT or the development of piruet-type arrhythmias (eg, congenital lengthening syndrome Q D); heart disease (heart failure, myocardial infarction, bradycardia); electrolyte imbalance (eg, hypokalemia, hypomagnesemia); simultaneous use of drugs that extend the interval QT (including antiarrhythmic IA and III classes, tricyclic antidepressants, macrolides, neuroleptics); simultaneous application with inhibitors of isoenzymes CYP 450 1A2 (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine and etc).

Pregnancy and lactation:

Ciprofloxacin is contraindicated in pregnancy and breastfeeding. If it is necessary to use ciprofloxacin in the mother during lactation, breastfeeding should be terminated before treatment begins.

Dosing and Administration:

In the form of intravenous infusion for at least 60 minutes. The infusion solution should be injected slowly into a large vein, which will prevent complications at the site of administration.

The infusion solution can be administered alone or together with other compatible infusion solutions. The solution for infusion can be mixed with 0.9% sodium chloride solution, Ringer's and Ringer's lactate solution, 5% and 10% dextrose solution.10% fructose solution, as well as with a solution containing 5% dextrose solution with 0.225-0.45% sodium chloride solution.

The solution obtained after mixing ciprofloxacin with compatible infusion solutions should be used as soon as possible because of the sensitivity of the drug to light and to maintain the sterility of the solution. If compatibility with another infusion solution / drug is not confirmed, the infusion solution of ciprofloxacin should be administered separately. Visible signs of incompatibility are precipitation, clouding or discoloration of the solution. Incompatibility takes place if the solutions / preparations are physically or chemically unstable at the pH values of the infusion solution of ciprofloxacin (for example, penicillins, heparin), and in particular with solutions that alter the pH values to the alkaline side (the pH of the ciprofloxacin solution is 3 , 5-4.5).

When storing the infusion solution of ciprofloxacin at low temperatures, a precipitate may form which dissolves at room temperature. Therefore, it is not recommended to store the infusion solution in the refrigerator and freeze.

The solution of ciprofloxacin is light-sensitive, so the vial should be removed from the box only before use.

Only clean clear solution should be used.

Adults:

For respiratory infections (depending on the severity of the infection and the patient's condition) - from 400 mg twice a day to 400 mg 3 times a day:

With infections of the genitourinary system: acute uncomplicated - from 200 mg twice a day to 400 mg twice a day, complicated - from 400 mg twice a day to 400 mg 3 times a day:

With adnexitis, chronic bacterial prostatitis, orchitis, epididymitis - from 400 mg twice a day to 400 mg three times a day;

With diarrhea - 400 mg twice a day:

With other infections (see section "Indications for use") - 400 mg 2 times a day.

Particularly serious infections that pose a threat to life, especially if available Pseudomonas spp., Staphylococcus spp., Streptococcus spp., including pneumonia caused by Streptococcus spp, recurrent infections in cystic fibrosis, infections of bones and joints, septicemia, peritonitis - 400 mg 3 times a day.

With a pulmonary form of anthrax (treatment and prevention) - 400 mg 2 times a day.

To patients of advanced age prescribe lower doses of ciprofloxacin, depending on the severity of the infection and the creatinine clearance rate.

Children:

In the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years - 10 mg / kg 3 times a day (maximum daily dose of 1200 mg). The duration of the course of treatment is 10-14 days.

With a pulmonary form of anthrax (prevention and treatment) - 10 mg / kg 2 times a day. The maximum single dose is 400 mg. daily - 800 mg. The total duration of treatment is 60 days.

Dosing in special cases:

In chronic renal failure: with a creatinine clearance of 30-60 ml / min / 1.73 square meters or a serum creatinine concentration of 1.4 to 1.9 mg / 100 ml, the maximum daily dose is 800 mg. When creatinine clearance is less than 30 ml / min / 1.73 square meters or serum creatinine concentration is above 2 mg / 100 ml and during hemodialysis the maximum daily dose is 400 mg. With hemodialysis ciprofloxacin injected after a hemodialysis session.

With hepatic insufficiency: in patients with hepatic insufficiency, dose adjustment is not required.

With peritoneal dialysis, the infusion solution is added to dialysate (intraperitoneally) at a dose of 50 mg per liter of dialysate 4 times a day (every 6 hours).

Average course of treatment: 1 day - with acute uncomplicated gonorrhea; up to 7 days - with infection of the kidneys, urinary tract and abdominal cavity; no more than 2 months - with osteomyelitis and 7-14 days - with all other infections.

With streptococcal infections, due to the danger of late complications, treatment should last at least 10 days.

In infections caused by Chlamydia spp., treatment should also be continued for at least 10 days.

Treatment for pulmonary form of anthrax in adults and children should be administered immediately after suspected or confirmed infection. The total duration of treatment with ciprofloxacin in pulmonary form of anthrax is 60 days. In patients with immunodeficiency treatment spend during the entire period of neutropenia. Treatment should be carried out at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to the frequency of their development: very often (> 1/10), often (1/10 to 1/100), infrequently (1 / 100-1 / 1000), rarely (1 / 1000-1 / 10000). very rarely (<1/10000), the frequency is unknown (the frequency can not be determined based on the available data).

Infectious and parasitic diseases:

Infrequently: fungal superinfections;

Rarely: pseudomembranous colitis (in very rare cases with possible fatal outcome).

Violations from the blood and lymphatic system:

Infrequently: eosinophilia;

Rarely; anemia, neutropenia. thrombocytopenia. leukocytosis, thrombocythemia. leukopenia;

Rarely: hemolytic anemia, agranulocytosis, pancytopenia (life threatening), oppression of bone marrow hematopoiesis (life threatening).

Immune system disorders:

Rarely: allergic reactions, allergic edema / angioedema;

Rarely: anaphylactic reactions, anaphylactic shock (life threatening), serum sickness.

Disorders from the metabolism and nutrition:

Infrequently: decreased appetite and intake of food;

Rarely: hypoglycemia, hyperglycemia.

Disorders of the psyche:

Infrequently: psychomotor hyperactivity / agitation;

Rarely: confusion, disorientation, anxiety, depression (which can lead to very damaging behavior, such as suicidal behavior / thoughts, as well as suicide attempt or suicide), nightmares, hallucinations;

Rarely: psychotic depression reactions (which can lead to self-damaging behavior, such as suicidal behavior / thoughts, as well as suicide attempt or suicide).

Disturbances from the nervous system:

Infrequently: dizziness, headache, sleep disturbance, taste disorder;

Rarely: tremor, convulsions (including epileptic seizures), vertigo, hypoesthesia, paresthesia and dysesthesia;

Rarely: migraine, impaired coordination of movements, impaired sense of smell, hyperesthesia, benign intracranial hypertension;

Frequency unknown: peripheral neuropathy and polyneuropathy.

Disturbances on the part of the organ of sight:

Rarely: impaired vision:

Rarely: violation of color perception.

Hearing disorders and labyrinthine disorders:

Rarely: temporary hearing loss, noise in the ears, loss of hearing.

Heart Disease:

Rarely: tachycardia;

Frequency unknown: lengthening the interval QT, ventricular arrhythmias (including the "pirouette" type).

Vascular disorders:

Rarely: vasodilation, lowering blood pressure, "tides" of blood to the face:

Rarely: vasculitis.

Disturbances from the respiratory system, chest and mediastinal organs:

Rarely: violation of breathing (including bronchospasm), dyspnea.

Disorders from the gastrointestinal tract:

Often: nausea, diarrhea;

Infrequently: indigestion, vomiting, abdominal pain, flatulence;

Rarely: pancreatitis.

Disturbances from the liver and bile ducts:

Infrequently: increased activity of "liver" transaminases. increased bilirubin concentration;

Rarely: impaired liver function, jaundice, hepatitis (non-infectious);

Rarely: hepatonecrosis (progressing to life-threatening liver failure).

Disturbances from the skin and subcutaneous tissues:

Infrequently: itching, rashes, hives:

Rarely: Photosensitivity reactions, blistering;

Rarely: spot hemorrhages on the skin (petechia), multiforme exudative erythema (including Stevens-Johnson syndrome), erythema nodosum, toxic epidermal necrolysis (Lyell syndrome):

Frequency unknown: generalized pustular exanthema.

Disturbances from musculoskeletal and connective tissue:

Infrequently: arthralgia, musculoskeletal pain (including pain in the limbs, back pain, chest pain);

Rarely: myalgia, arthritis, tendovaginitis, increased muscle tone, muscle cramps;

Rarely: muscle weakness, tendonitis, tendon ruptures (mainly Achilles), exacerbation of myasthenia gravis symptoms.

Disorders from the kidneys and urinary tract:

Infrequently: impaired renal function;

Rarely: Kidney failure, hematuria, crystalluria, tubulointerstitial nephritis;

General disorders and disorders at the site of administration:

Often: reactions at the injection site;

Infrequently: fever;

Rarely: swelling, increased sweating;

Rarely: violation of gait.

Impact on the results of laboratory and instrumental studies:

Infrequently: increased activity of alkaline phosphatase;

Rarely: a change in the concentration of prothrombin, an increase in the activity of amylase;

Frequency not known: increased international normalized ratio (in patients receiving vitamin K antagonists).

The frequency of development of the following side effects with intravenous administration and with the use of stepwise therapy of ciprofloxacin (with intravenous administration of the drug with subsequent ingestion) is higher than with oral administration:

Often: vomiting, increased activity of "liver" transaminases, rash;

Infrequently: thrombocytopenia, thrombocythemia, confusion and disorientation, hallucinations, paresthesia and dysesthesia, cramps, vertigo, blurred vision, hearing loss, tachycardia, vasodilation,decrease in arterial pressure, reversible violations of liver function, jaundice, kidney failure, edema;

Rarely: pancytopenia, bone marrow depression, anaphylactic shock, psychiatric reactions, migraine, impaired sense of smell, hearing impairment, vasculitis, pancreatitis, necrosis of liver tissue, petechia, tendon rupture.

Children: children often reported on the development of arthropathy.

If any of the side effects listed in the manual are aggravated, or you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms: nausea, vomiting, confusion, mental agitation.

Treatment: the specific antidote is unknown. It is necessary to carefully monitor the patient's condition, conduct symptomatic therapy, and ensure sufficient fluid intake. In order to prevent the development of crystallaria, it is recommended to monitor renal function, including pH and acidity of urine. With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted.

Interaction:

Medicinal products that cause lengthening of the interval QT

Caution should be exercised with the simultaneous use of ciprofloxacin, as well as other fluoroquinolones, in patients receiving medications that cause lengthening of the interval QT (for example, antiarrhythmic drugs of Class IA and III, tricyclic antidepressants, macrolides and antipsychotics) (see section "Special instructions").

Theophylline

Simultaneous use of ciprofloxacin and preparations containing theophylline, can cause an undesirable increase in the concentration of theophylline in the blood plasma and, accordingly, the occurrence of theophylline-induced phenomena; in very rare cases, these side effects can be life threatening to the patient. If the simultaneous use of these two drugs is inevitable, it is recommended that continuous monitoring of the concentration of theophylline in the blood plasma and, if necessary, reduce the dose of theophylline.

Other xanthine derivatives

Simultaneous use of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) may lead to an increase in the concentration of xanthine derivatives in the blood serum.

Phenytoin

With the simultaneous use of ciprofloxacin and phenytoin, there was a change (increase or decrease) in the content of phenytoin in the blood plasma. In order to avoid the occurrence of convulsions associated with a decrease in the concentration of phenytoin, and also to prevent undesirable phenomena associated with a phenytoin overdose when ciprofloxacin is discontinued, it is recommended to monitor phenytoin therapy in patients taking both drugs, including the determination of the phenytoin content in the blood plasma throughout the whole period of simultaneous application of both drugs and a short time after the completion of combination therapy.

Nonsteroidal anti-inflammatory drugs

The combination of very high doses of quinolones (DNA-gyrase inhibitors) and some non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) can provoke convulsions.

Cyclosporin

With the simultaneous use of ciprofloxacin and drugs containing ciclosporin, a transient transient increase in the concentration of creatinine in the blood plasma was observed. In such cases, the concentration of creatinine in the blood should be determined twice a week.

Oral hypoglycemic agents

With the simultaneous use of ciprofloxacin and oral hypoglycemic agents, mainly sulfanylureas (for example, glibenclamide, glimepiride), the development of hypoglycemia may be due to an increase in the effect of oral hypoglycemic agents (see section "Side effect").

Probenecid

Probenecid slows the rate of excretion of ciprofloxacin by the kidneys. Simultaneous use of ciprofloxacin and preparations containing probenecid, leads to an increase in the concentration of ciprofloxacin in the blood serum.

Methotrexate

With the simultaneous use of methotrexate and ciprofloxacin, the renal tubular transport of methotrexate may be slowed, which may be accompanied by an increase in the concentration of methotrexate in the blood plasma. This may increase the likelihood of side effects of methotrexate. In this regard, for patients receiving concomitant therapy with methotrexate and ciprofloxacin, careful monitoring must be established.

Tizanidine

As a result of a clinical study involving healthy volunteers with simultaneous use of ciprofloxacin and drugs containing tizanidine, an increase in the concentration of tizanidine in blood plasma: an increase in the maximum concentration (FROM_max) in 7 times (from 4 to 21 times), an increase in the area under the pharmacokinetic curve "concentration-time" (AUC) - 10 times (from 6 to 24 times). With an increase in the concentration of tizanidine in the serum, hypotensive (lowering blood pressure) and sedative (drowsiness, lethargy) side effects are associated. Thus, the simultaneous use of ciprofloxacin and preparations containing tizanidine. it is contraindicated.

Duloxetine

During the clinical trial, it was shown that the simultaneous use of duloxetine and potent inhibitors of isoenzyme CYP450 1A2 (such as fluvoxamine) can lead to an increase AUC and FROM_max duloxetine. Despite the lack of clinical data on the possible interaction with ciprofloxacin. it is possible to predict the likelihood of such interaction with the simultaneous use of ciprofloxacin and duloxetine.

Ropinirole

The simultaneous use of ropinirole and ciprofloxacin, a moderate isoenzyme inhibitor CYP450 1A2, leads to an increase FROM_max and AUC ropinirole by 60% and 80% respectively. It is necessary to monitor the side effects of ropinirole during its combined use with ciprofloxacin and for a short time after completion of the combination therapy.

Lidocaine

In a study on healthy volunteers, it was found that the simultaneous use of drugs containing lidocaine. and ciprofloxacin. moderate isoenzyme inhibitor CYP450 1A2, leads to a decrease in lidocaine clearance by 22% when administered intravenously. Despite the good tolerability of lidocaine, simultaneous use with ciprofloxacin may increase the side effects due to interaction.

Clozapine

With the simultaneous use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively. It is necessary to monitor the patient's condition and, if necessary, adjust the dosage regimen of clozapine during its simultaneous use with ciprofloxacin and for a short time after completion of the combination therapy.

Sildenafil

With the simultaneous use in healthy volunteers, ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg there was an increase FROM_max and PPC sildenafil in 2 times. In this regard, the application of this combination is possible only after the evaluation of the benefit / risk ratio.

Antagonists of vitamin K

The combined use of ciprofloxacin and vitamin K antagonists (eg, warfarin, acenocoumarol, fenprocumone, fluindone) may lead to an increase in their anticoagulant effect. The magnitude of this effect may vary depending on the concomitant infections, age and general condition of the patient, so it is difficult to assess the effect of ciprofloxacin on increasing INR (the international normalized ratio). It is often enough to monitor INR during joint use of ciprofloxacin and vitamin K antagonists, and also for a short time after the completion of combination therapy.

Special instructions:

Severe infections, staphylococcal infections and infections caused by gram-positive and anaerobic bacteria

Monotherapy with ciprofloxacin is not a suitable method for treating severe infections, including when suspected of infection caused by gram-positive and / or anaerobic microorganisms.In such cases, the appointment of appropriate antibacterial drugs.

Infections due to Streptococcus pneumonia

Ciprofloxacin is not recommended for the treatment of infections caused by Streptococcus pneumonia, because of its insufficient effectiveness in relation to this pathogen.

Infections of the reproductive tract

In the treatment of patients with epididymoortitis and pelvic inflammatory disease, it should be borne in mind that these infections can be caused by strains Neisseria gonorrhoeae, resistant to fluoroquinolones. The administration of ciprofloxacin for the treatment of such patients is only possible in combination with other antibacterial drugs active against this pathogen (eg, cephalosporins). If ciprofloxacin therapy is not observed within 3 days of clinical improvement of the patient's condition, therapy should be changed.

Urinary tract infections

Local data on resistance to fluoroquinolones Escherichia coli (the most frequent pathogen of urinary tract infections).

Infections of the abdominal cavity

To date, data on the effectiveness of ciprofloxacin for patients with post-operative infections of the abdominal cavity are limited.

Pulmonary form of anthrax

Data on the effectiveness of ciprofloxacin in the treatment of this disease are based on the sensitivity of microorganisms in experiments in vitro and on animals. The data on the use of the drug for the treatment of the disease in humans is limited, one should refer to national or international recommendations.

Heart Disease

Ciprofloxacin may cause lengthening of the interval QT. Given that women are characterized by a large average duration of the interval QT compared with men, they are more sensitive to drugs that cause lengthening of the interval QT. In elderly patients, too, there is an increased sensitivity to the action of drugs, which causes lengthening of the interval QT. It should be used with caution ciprofloxacin in combination with drugs that extend the interval QT (for example, antiarrhythmic drugs classes IA and III, tricyclic antidepressants, macrolides, neuroleptics), or in patients with an increased risk of developing pirouette-type arrhythmias (eg, congenital lengthening of the interval QT, uncorrelated hypokalemia, hypomagnesemia), in patients with heart disease (heart failure, myocardial infarction, bradycardia).

Application in children and adolescents

It was found that ciprofloxacin, like other drugs of this class, causes arthropathy of large joints in animals.

When analyzing the current data on the safety of ciprofloxacin in children under 18 years of age, most of whom have cystic fibrosis of the lungs, there is no association between cartilage damage and joints and drug administration.

Ciprofloxacin should be prescribed to children and adolescents in strict accordance with the recommendations for treatment of patients of this age category.

Patients with cystic fibrosis drug should be appointed by specialists who have experience in treating children with this pathology. It is not recommended to use ciprofloxacin in children for the treatment of other diseases, except for the treatment of complications of cystic fibrosis associated with Pseudomonas aeruginosa and for the treatment and prevention of the pulmonary form of anthrax (after suspected or proven infection Bacillus anthracis). Due to the risk of developing undesirable effects from the bones and joints, the drug should be given to children only after a careful assessment of the potential benefit and risk of therapy.

Allergic reactions

Sometimes after the introduction of the first dose of ciprofloxacin, allergic reactions may develop, which should be reported immediately to the doctor. In rare cases, after the first application, anaphylactic reactions may develop, including anaphylactic shock. In these cases, ciprofloxacin should be discontinued immediately and appropriate treatment should be performed.

Gastrointestinal tract

If severe and prolonged diarrhea occurs during or after the administration of ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of the appropriate treatment (vancomycin inside in the appropriate dose). Contraindicated use of drugs that inhibit intestinal peristalsis.

Traveler's Diarrhea

Before prescribing the drug should take into account the data on the prevalence of resistance to fluoroquinolones in countries visited by the patient before the development of the disease.

Hepatobiliary system

When ciprofloxacin was used, cases of liver necrosis and life-threatening liver failure were noted. When the following symptoms appear: anorexia, jaundice, dark urine, itching, abdominal pain - the drug should be discontinued.

Musculoskeletal system

When using ciprofloxacin, there may be cases of tendinitis and rupture of tendons (mainly Achilles tendon), sometimes bilateral, within the first 48 hours after the initiation of therapy. Inflammation and tendon rupture can occur even a few months after discontinuation of ciprofloxacin treatment.

At the first signs of tendonitis (painful swelling in the joint area, inflammation), the use of ciprofloxacin should be discontinued, exclude physical activity, as there is a risk of rupture of the tendon, and consult a doctor.

In elderly patients with tendon diseases, or previously treated with glucocorticosteroids, there is an increased risk of rupture of tendons (mainly Achilles tendon).

Ciprofloxacin should be used with caution in patients who have a history of tendon disease associated with the administration of quinolones.

Patients with myasthenia gravis gravis Ciprofloxacin should be used with caution because of the possible exacerbation of symptoms.

Infections of bones and joints

When treating the infection of the specified location ciprofloxacin should be administered in combination with other antibacterial drugs, taking into account the results of the microbiological study.

Nervous system

Ciprofloxacin, like other fluoroquinolones, can reduce the threshold of convulsive readiness and provoke the development of seizures until the development of epileptic status. Patients with epilepsy, expressed atherosclerosis of cerebral vessels, cerebral circulation disorder (in the anamnesis), mental illnesses, reduced threshold of convulsive readiness, convulsions (in the anamnesis), with organic lesions of the brain due to the possibility of developing side reactions from the side of the central nervous system, ciprofloxacin It should be used only in those cases when the expected clinical effect exceeds the possible risk.

In some cases, adverse reactions from the CNS may occur after the first use of the drug.

In very rare cases, psychosis may manifest as suicidal attempts, including those that have occurred.

If seizures occur, mental reactions should immediately stop using ciprofloxacin and inform the doctor about it.

With the use of ciprofloxacin, cases of development of sensory and sensorimotor polyneuropathy, hypesthesia, and dysesthesia were noted. If symptoms such as pain, burning, tingling, numbness, weakness occur, the drug should be discontinued to prevent the development of irreversible changes.

Hypoglycaemia

As with the intake of other fluoroquinolones. when using ciprofloxacin, it is possible to reduce the concentration of glucose in the blood plasma, mainly in patients with diabetes, especially the elderly. When ciprofloxacin is prescribed, patients with diabetes mellitus should carefully monitor the concentration of glucose in the blood plasma.

Skin covers

When ciprofloxacin is used, a photosensitization reaction may occur, so patients should avoid contact with direct sunlight and ultraviolet radiation. Treatment should be discontinued if symptoms of photosensitivity are noted.

Isozymes of cytochrome P450

It is known that ciprofloxacin is a moderate inhibitor of isoenzyme CYP450 1A2. Caution should be exercised when using ciprofloxacin and preparations metabolized by these enzymes, such as theophylline, methylxanthine, caffeine, duloxetine, clozapine. ropinirole and olanzapine , etc., as an increase in the concentration of these drugs in the blood plasma, caused by inhibition of their metabolism by ciprofloxacin. can cause specific undesirable reactions. It is necessary to carefully monitor the status of patients for symptoms of overdose, as well as to monitor the concentration of drugs in the blood (for example, theophylline).

The combined use of ciprofloxacin and tizanidine is contraindicated.

Local Reactions

With iv administration of the drug, reactions may occur at the site of administration (edema, pain). This reaction occurs more often if the infusion time is 30 minutes or less. The reaction takes place after the end of the injection and is not a contraindication for the subsequent administration of the drug, unless its course is complicated.

Impaired renal function and urinary system

As ciprofloxacin is excreted mainly by the kidneys, in patients with impaired renal function, a correction of the dose of the drug is required (see the section "Dosing and Administration").When ciprofloxacin was used, cases of crystalluria were reported. To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake and maintenance of acid urine reaction are also necessary.

Deficiency of glucose-6-phosphate dehydrogenase

In patients with a deficiency of glucose-6-phosphate dehydrogenase, ciprofloxacin, hemolytic reactions were noted. The appointment of ciprofloxacin in this category of patients is possible only if the potential benefit of using the drug exceeds the possible risk. Careful monitoring of the patient's condition is necessary.

Resistance

During and after the completion of the course of ciprofloxacin treatment, there are possible the phenomena of excessive growth of strains of resistant microorganisms, including without clinical signs of superinfection. The risk of the emergence of resistant strains is particularly high in the case of long-term therapy, the treatment of nosocomial (nosocomial) infections and / or in case of infections caused by representatives Staphylococcus spp. and Pseudomonas spp.

With simultaneous intravenous administration of ciprofloxacin and preparations for general anesthesia from the group of barbituric derivativesacid requires constant monitoring of heart rate, blood pressure, ECG.

In vitro in laboratory tests ciprofloxacin suppresses growth Mycobacterium spp., which can lead to false negative results in the diagnosis of this pathogen in patients taking ciprofloxacin.

It is necessary to take into account the content of sodium chloride in the solution of ciprofloxacin in the treatment of patients in whom sodium intake is limited (heart failure, kidney failure, nephrotic syndrome).

Effect on the ability to drive transp. cf. and fur:

Fluoroquinolones, including ciprofloxacin, can disrupt the ability of patients to drive a car and engage in other potentially dangerous activities requiring increased attention and speed of psychomotor reactions, due to the effect on the central nervous system. Therefore, during treatment should refrain from engaging in potentially dangerous activities that require increased attention and speed of mental and motor reactions.

Form release / dosage:

Solution for infusions, 0,2%.

Packaging:

For 100 ml of the drug in bottles of polypropylene with a loop-holder,ukuporennye polypropylene lids with rubber lining and equipped with a cap with a tear-off ring for opening, welded on the bottle.

For 1 bottle together with instructions for medical use are placed in a consumer package (a pack of cardboard).

For hospitals

For 100 ml of the drug in polypropylene bottles with a holder loop, sealed with polypropylene lids with a rubber lining and equipped with a cap with a tear-off ring for opening, welded onto the vial.

For 120 vials, together with an equal number of instructions for medical use, are placed in a group package (carton box).

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003895

Date of registration:10.10.2016

Expiration Date:10.10.2021

The owner of the registration certificate:Kelun-Kazfarm, TOOKelun-Kazfarm, TOO The Republic of Kazakhstan

Manufacturer: & nbsp

Kelun-Kazpharm, TOO The Republic of Kazakhstan

Information update date: & nbsp28.10.2016

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)