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

Excipients: sodium chloride - 9.0 mg; disodium edetate dihydrate (in terms of disodium edetate) 0.10 mg; Lactic acid (in terms of 100% substance) - 0.64 mg; citric acid monohydrate - 0.12 mg; hydrochloric acid solution of 1 M or sodium hydroxide solution of 1 M - to a pH of 3.5-4.6; water for injection up to - 1 ml.

Description:

Transparent, colorless or slightly greenish-yellow liquid.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

Ciprofloxacin is a synthetic broad-spectrum antimicrobial agent from the group of fluoroquinolones.

Mechanism of action

Ciprofloxacin has activity in vitro for a wide range of gram-negative and gram-positive microorganisms. The bactericidal action of ciprofloxacin is effected by inhibiting bacterial topoisomerases II (topoisomerase II (DNA gyrase) and topoisomerase IV), which are necessary for replication, transcription, repair and recombination of bacterial DNA.

Mechanisms of resistance

Resistance in vitro to ciprofloxacin is often caused by point mutations of bacterial topoisomerases and DNA gyrase and develops slowly, through multistage mutations.

Single mutations can lead to a decrease in sensitivity rather than to the development of clinical stability, but multiple mutations mainly lead to the development of clinical resistance to ciprofloxacin and to cross-resistance to quinolone drugs.

Resistance to ciprofloxacin, as well as to many other antibiotics, can be formed as a result of a decrease in the permeability of the bacterial cell wall (as is often the case with Pseudomonas aeruginosa) and / or activation of excretion from the microbial cell (efflux). The development of resistance due to the encoding gene localized on plasmids 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 testing susceptibility to ciprofloxacin, approved by the European Committee on the definition 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	Resistant
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 meningitidis	≤0,03	>0,06
Boundary values, not related to microbial species4	≤0,5	>1

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

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

³Strains 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 infections caused by N. influenzae, no.

⁴Boundary values not associated with microbial species were determined mainly on the basis of pharmacokinetics / pharmacodynamics data and are not dependent 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 MIC (mg / l) and diffusion testing (mm) using discs

Microorganism	Sensitive	Ppointerstitial	Resistant
Enterobacteriaceae	<l^a	2^a	>4^a
Enterobacteriaceae	>21^b	16-20^b	<15^b
Pseudomonas aeruginosa and other non-family bacteria Enterobacteriaceae	<1^a	2^a	>4^a
	>21⁶	16-20^b	<15^b
Staphylococcus spp.	<1^a	2^a	>4^a
Staphylococcus spp.	>21^b	16-20^b	<15^b
Enterococcus spp.	<1^at	2^a	>4^a
Enterococcus spp.	>21⁶	16-20^b	<15^b
Haemophilus spp.	<1^at	--	--
Haemophilus spp.	>21^g	--	--
Neisseria gonorrhoeae	<0,06^d	0,12-0,5^d	>1^d
Neisseria gonorrhoeae	>41^d	28-40^d	<27^d
Neisseria meningitidis	<0,03^e	0,06^e	>0,12^e
Neisseria meningitidis	>35^f	33-34^f	<32 ^f
Bacillus anthracis Yersinia pestis	<0,25^a	-	-
Francisella tularensis	<0,5^z	-	-

a. This reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (SAMIV) 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 h 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 to Haemophilus influenzae and Haemophilus parainjluenzae using a broth test medium for Haemophilus spp. (NTM), which is incubated with air access at a temperature of 35 ± 2 ° C for 20-24 hours.

in 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.

e. 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 within 20-24 hours.

e. This reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (SLMWH) supplemented with 5% sheep blood which is incubated in 5% CO2 at 35 ± 2 ° C for 20-24 hours.

f. This reproducible standard applies only to broth dilutions using cationic corrected Mueller-Hinton broth (SAMS) with the addition of a specific 2% growth additive which is incubated with air access at 35 ± 2 ° C for 48 hours.

In vitro sensitivity to ciprofloxacin

For certain strains, the spread of acquired resistance may vary depending on the geographical region and over time. In this regard, when testing the sensitivity of a strain, it is desirable to have local information on resistance, especially when treating severe infections. If the local prevalence of resistance is such that the use of the drug, at least for several types of infections, is questionable, it is necessary consult with an expert.

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

Aerobic Gram-positive microorganisms: Bacillus ant hr as is, Staphylococcus aureus (methicillin-sensitive), Staphylococcus saprophyticus, Streptococcus spp.

Aerobic Gram-negative microorganisms: Aeromonas spp., Moraxella catarrhal is, Brucella spp.. Neisseria meningitidis, Citrohacter koseri, Pasteurella spp., Francisella tularensis, 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 hominis, Mycoplasma pneumonia.

Was demonstrated varying power sensitivity to ciprofloxacin for the following microorganisms: Acinetobacter baumanii, Burkholderia cepacia, Campylobacter spp., Citrobacter freundii. Enterococcus faecal is, 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, what natural resistance to ciprofloxacin have the Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enteroccus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealyticum, anaerobic microorganisms (behind exclusion Mobiluncus spp., Peptostreptococus spp., Propionibacterium acnes).

Pharmacokinetics:

Suction

After intravenous (IV) administration, the maximum concentration of ciprofloxacin in the blood plasma (Cmax) is reached 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

Ciprofloxacin is biotransformed in the liver. In the blood can be found 4 metabolites of ciprofloxacin in small concentrations: diethylciprofloxacin (M1), sulfosiprofloxacin (M2), oxocycloploxacin (M3), formyl ciprofloxacin (M4), 3 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. The renal clearance is 0.18-0.3 l / h / kg, the total 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 renal function, the half-life period is usually 3-5 hours. If the renal function is impaired, the elimination half-life increases.

Children

In a study in children, the value of Cmah and the area under the curve "concentration-time" (AUC) did not depend on age. A marked increase in Cmah and AUC with repeated use of the drug (at a dose of 10 mg / kg 3 times a day) was not observed. In 10 children with severe sepsis aged less than 1 year, the value of Cma 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). Values AUC in the respective 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 expected average half-life is approximately 4-5 hours.

Indications:

Uncomplicated and complicated infections caused by susceptible to ciprofloxacin microorganisms.

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.;

- middle ear infections (otitis media), sinus congenital sinuses (sinusitis), especially if these infections are caused by gram-negative microorganisms, including Pseudomonas aeruginosa or Staphylococcus spp.;

- eye infections;

- infections of the kidneys and urinary tract;

- infection of the genital organs, including adnexitis, gonorrhea, prostatitis;

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

- skin and soft tissue infections;

- infections of bones and joints;

- 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).

Children

- treatment of complications caused by Pseudomonas aeruginosa, in children from 5 to 17 lay with cystic fibrosis of the lungs;

- 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.

Contraindications:

- Hypersensitivity to ciprofloxacin and other preparations of the group of fluoroquinolones, as well as to auxiliary substances;

- simultaneous administration with tizanidine due to clinically significant side effects associated with an increase in the concentration of tizayizidin in the blood (risk of pronounced reduction in blood pressure, drowsiness);

- pseudomembranous colitis;

- Children under 18 years of age (before the completion of the formation of the skeleton, 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 the pulmonary form of anthrax);

- Pregnancy;

- the period of breastfeeding.

Carefully:

Severe atherosclerosis of cerebral vessels, impaired cerebral circulation, increased risk of lengthening the interval QT or the development of piruet-type arrhythmias (eg, congenital lengthening syndrome QT, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), deficiency of glucose-6-phosphate dehydrogenase; 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 CYP450 1A2, (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine); patients with a history of tendon damage associated with the use of quinolones, mental illness (depression, psychosis), diseases central nervous system (CNS): epilepsy, lowering the threshold convulsive readiness (or convulsive fits in the anamnesis), organic lesions of the brain or stroke; marked renal and / or liver failure; myasthenia gravis gravis; elderly age.

Pregnancy and lactation:

Ciprofloxacin is contraindicated during pregnancy and breastfeeding.

Dosing and Administration:

Intravenously.

Recommended dosing regimen for adults:

- For infections of the respiratory tract (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 2 times a day;

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

- Especially serious infections that pose a threat to life, especially if there is Pseudomonas spp., Staphylococcus spp. or 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.

- Pulmonary form of anthrax (treatment and prevention) - 400 mg twice a day, 60 days.

Children and adolescents:

- infection in cystic fibrosis - 10 mg / kg body weight 3 times a day (maximum dose of 400 mg);

- pulmonary form of anthrax (postcontact) - 10 mg / kg of body weight 2 times a day (maximum single dose - 400 mg).

Dosing regimen in elderly patients (after 65 years)

Older patients should be prescribed lower doses of ciprofloxacin, depending on the severity of the infection and the creatinine clearance rate.

Dosing regimen for adult patients with chronic renal failure:

- with clearance of creatinine from 30 to 60 ml / min / 1.73 m² or a serum creatinine concentration of 1.4 to 1.9 mg / 100 ml, the maximum daily dose of 800 mg. When the creatinine clearance is less than 30 ml / min / 1.73 m² or a serum creatinine concentration above 2 mg / 100 ml, the maximum daily dose is 400 mg.

Patients with renal insufficiency on hemodialysis:

- with clearance of creatinine from 30 to 60 ml / min / 1.73 m² or a serum creatinine concentration of 1.4 to 1.9 mg / 100 ml, the maximum daily dose of 800 mg;

- with clearance of creatinine below 30 ml / min / 1.73 m² or a serum creatinine concentration above 2 mg / 100 ml (severe renal failure), the maximum daily dose is 400 mg.

With hemodialysis ciprofloxacin injected after a hemodialysis session.

In patients with renal failure with prolonged outpatient peritoneal dialysis: the infusion solution is added to the dialysate (intraperitoneally) at a dose of 50 mg per liter of dialysate 4 times a day (every 6 hours).

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

The dosage regimen in children with impaired functions of the nights and liver has not been studied. Mode of application

The drug should be administered intravenously drip for at least 60 minutes.Infusion solution should be injected slowly into a large vein, which helps prevent complications at the site of infusion. The infusion solution can be administered alone or together with other compatible infusion solutions.

The infusion solution can be mixed with 0.9% sodium chloride solution, Ringer's and Ringer's lactate solution, 5% and 10% dextrose solution, 10% fructose solution, and also a solution containing 5% dextrose solution with 0.225-0.45% solution of sodium chloride.

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 occurs with all solutions / preparations that are physically or chemically unstable at the pH values of the infusion solution of ciprofloxacin (eg, penicillins,heparin solution), and in particular with solutions that change the pH values to the alkaline side (the pH of the infusion solution of ciprofloxacin is 3.5 to 4.6).

The solution for infusions is light-sensitive, so the bottle should be removed from the package only before use. When stored 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.

When opening the bottle, it is recommended to pierce the cap in the area of the center ring. Piercing outside the center ring can cause damage to the cap.

Only clean clear solution should be used.

Duration of therapy

The duration of treatment depends on the severity, clinical course and cure of the disease. Treatment should be carried out at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

Average duration of treatment (adults):

- with acute uncomplicated gonorrhea - 1 day;

- with infections of the kidneys, urinary tract and abdominal cavity - up to 7 days;

- with osteomyelitis - no more than 2 months;

- with streptococcal infections (due to the danger of late complications) - not less than 10 days;

- in patients with immunodeficiency treatment is carried out throughout the neutropenia period;

- with all other infections - 7-14 days.

Average duration of treatment (children and adolescents):

- in the treatment of complications of cystic fibrosis of the lungs caused by Pseudomonas aeruginosa (in patients from 5 to 17 years) - 10-14 days.

Side effects:

The undesirable reactions listed below were classified as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10,000 , <1/1000), very rarely (<10 000), the frequency is unknown.

Unwanted reactions, which were recorded only during post-marketing observations, whose frequency was not evaluated, are designated as "frequency unknown."

Often	Infrequently	Rarely	Rarely	Frequency unknown
INFECTIOUS AND PARASITARY DISEASES
	Fungal superinfections	Pseudomembranous colitis (in very rare cases - with possible fatal outcome)
FROM THE SIDE OF THE SYSTEM OF BLEEDING
	Eosinophilia	Leukopenia Anemia Neutropenia Leukocytosis Thrombocytopenia Thrombocythemia	Hemolytic anemia Agranulocytosis Pancytopenia (life threatening) Oppression of the bone marrow (life threatening)
FROM THE SIDE OF THE IMMUNE SYSTEM
		Allergic reactions Allergic Edema / Angioedema	Anaphylactic reactions Anaphylactic shock (life-threatening) Serum sickness
FROM THE SIDE OF EXCHANGE OF SUBSTANCES AND NUTRITION
	Decreased appetite and intake of food	Hyperglycaemia Hypoglycaemia
MENTAL DISORDERS
	Psychomotor hyperactivity / agitation	Confusion and disorientation Anxiety Disturbance of dreams (nightmares) Depression (which can lead to self-damaging behavior, such as suicidal behavior / thoughts, as well as attempted suicide or suicide) Hallucinations	Psychotic reactions (which can lead to self damage the topic of behavior, such as suicidal behavior / thoughts, as well as attempted suicide or failed suicide)
FROM THE SIDE OF THE CENTRAL NERVOUS SYSTEM
	Headache Dizziness Sleep disturbance Disturbance of taste	Paresthesia and dysesthesia Hypesesia Tremor Convulsions (including epileptic seizures) Vertigo	Migraine Violation of coordination of movements Impaired smell Hyperesthesia Intracranial hypertension (benign)	Peripheral neuropathy and polyneuropathy
FROM THE PARTY OF THE ORGANIZATION
		Visual disturbances	Violation of color perception
FROM THE SIDE OF THE HEARING BODY AND LABYRINTH DISTURBANCES
		Noise in ears Hearing Loss	Hearing Impairment
FROM THE HEART OF THE HEART
		Tachycardia		QT interval extension Ventricular arrhythmias (including the "pirouette" type) *
FROM THE SIDE OF VESSELS
		Vasodilation Reduction of blood pressure Feeling of a "tide" of blood to the face	Vasculitis
FROM THE SIDE OF THE RESPIRATORY SYSTEM, BREAST CANCER AND MEDIUM ENVIRONMENT
		Disturbance of breathing (including bronchospasm)
FROM THE SIDE OF THE GASTROINTESTINAL TRACT
Nausea Diarrhea	Vomiting Abdominal pain Dyspepsia Flatulence		Pancreatitis
FROM THE LIVER'S side and the biliary tract
	Increased activity of "liver" transaminases Increased bilirubin concentration	Dysfunction of the liver Jaundice Hepatitis (non-infectious)	Necrosis of liver tissue (in extremely rare cases progressing to life-threatening liver failure)
FROM THE SIDE OF SKIN AND SUBCUTANEOUS TISSUE
	Rash Itching Hives	Photosensitivity Blistering	Petechia Multi-form erythema of small forms Nodal erythema Stevens-Johnson syndrome (malignant exudative erythema), including potentially life-threatening Lyell's syndrome (toxic epidermal necrolysis), including potentially life-threatening	Acute generalized pustular exanthema
FROM THE SIDE OF THE SKELETAL-MUSCULAR AND CONNECTING TISSUE
	Arthralgia	Myalgia Arthritis Increased muscle tone, muscle cramps	Muscle weakness Tendonitis Rupture of tendons (predominantly Achilles) Exacerbation of myasthenia gravis symptoms
FROM THE SIDE OF THE KIDNEY AND URINARY OUTLOOK
	Impaired renal function	Renal failure, hematuria Crystalluria Tubulointerstitial nephritis
GENERAL DISTURBANCES AND VIOLATIONS IN THE SITE OF INTRODUCTION
Reactions at the site of administration	Pain syndrome nonspecific etiology General malaise Fever	Edema Sweating (hyperhidrosis)	Violation of gait
LABORATORY INDICES
	Increased activity of alkaline phosphatase in the blood	Change in the concentration of prothrombin Increase of amylase activity		An increase in the international normalized relationship (INR) (in patients receiving vitamin K antagonists)

* More often in patients who are predisposed to the development of lengthening the interval QT (see section "Special instructions").

The frequency of development of the following adverse reactions with intravenous administration and with the use of stepwise therapy with 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, thrombocytopenia, confusion and disorientation, hallucinations, paresthesia and dysesthesia, convulsions, vertigo, visual impairment, hearing loss, tachycardia, vasodilation, lowering of blood pressure, reversible liver function disorders, jaundice, kidney failure, swelling
Rarely	Pancytopenia, bone marrow depression, anaphylactic shock, psychotic reactions, migraine, impaired sense of smell, hearing impairment, vasculitis, pancreatitis, liver tissue necrosis, petechiae, tendon rupture

Children

Children often reported on the development of arthropathy.

Overdose:

Symptoms

Nausea, vomiting, confusion, mental agitation.

Treatment

The specific antidote is unknown.It is necessary to carefully monitor the patient's condition, carry out 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 the class IA or class 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 adverse events; 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 it is necessary to determine the concentration of creatinine in the blood twice a week.

Oral hypoglycemic agents

With the simultaneous use of ciprofloxacin and oral hypoglycemic agents, mainly sulfonylureas (eg, glibenclamide, glimepiride), the development of hypoglycemia may be due to increased action 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 tubulartransport of methotrexate, 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 simultaneously 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 Cmah 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 blood serum, hypotensive (lowering blood pressure) and sedative (drowsiness, lethargy) are associated with side effects. Thus, the simultaneous use of ciprofloxacin and preparations containing tizanidine, is contraindicated.

Duloxetine

During clinical trials, 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 Cmduloxetine. Despite the lack of clinical data on the possible interaction with ciprofloxacin, it is possible to foresee 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 IA2, leads to an increase in Cmah and AUC ropinirole by 60% and 84%, 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, a moderate isoenzyme inhibitor CYP450 IA2, leads to a decrease in clearance of lidocaine by 22% with its intravenous administration. 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 of ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg, there was an increase in Cmax and the area under the curve 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, conditional gram-positive and anaerobic bacteria

In the treatment of severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents.

Infections, conditional Streptococcus pneumoniae

Ciprofloxacin is not recommended for the treatment of infections caused by Streptococcus pneumoniae, due to its limited effectiveness against the pathogen.

Infections of the reproductive tract

In genital infections presumably caused by strains Neisseria gonorrhoeae, resistant to fluoroquinolones, information about local resistance to ciprofloxacin should be taken into account and the sensitivity of the causative agent should be confirmed by laboratory tests.

Heart Disease

Ciprofloxacin influences lengthening of the interval QT (see section "Side effect").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 there is also an increased sensitivity to the action of drugs that cause lengthening of the interval QT. Therefore, you should use caution ciprofloxacin in combination with drugs that extend the interval QT (for example, antiarrhythmic drugs classes IA and III, tricyclic antidepressants, macrolides, and antipsychotics) (see "Interactions with Other Drugs"), or in patients at increased risk of lengthening the interval Q G or the development of arrhythmias such as "pirouette" (eg, with congenital syndrome of lengthening interval QT, unadjusted electrolyte imbalance, such as hypokalemia or hypomagnesemia, as well as heart diseases such as heart failure, myocardial infarction, bradycardia).

Application the children

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

When analyzing the currently available data on the safety of ciprofloxacin in children under 18 years of age, most of whom have cystic fibrosis of the lung, there is no association between cartilage damage and joints with drug administration. It is not recommended to use ciprofloxacin in children for the treatment of other diseases, except for the treatment of complications of cystic fibrosis of the lungs (in children from 5 to 17 years) associated with Pseudomonas aeruginosa, as well as for the treatment and prevention of the pulmonary form of anthrax (after suspected or proven infection Bacillus anthracis).

Hypersensitivity

Sometimes, after taking the first dose of ciprofloxacin, hypersensitivity to the drug may develop, including allergic reactions, which should be reported immediately to the treating physician (see the "Side effect" section). In rare cases, after the first application, anaphylactic reactions may occur up to anaphylactic shock. In these cases, the use of ciprofloxacin should be stopped immediately and appropriate treatment should be given.

Gastrointestinal tract

If a severe and prolonged diarrhea occurs during or after treatment with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded,which requires immediate withdrawal of the drug and the appointment of appropriate treatment (Vancomycin inside in a dose of 250 mg 4 times a day) (see section "Side effect"). Contraindicated in the use of drugs that suppress the intestinal peristalsis. Hepatobiliary system

When ciprofloxacin was used, there were cases of liver necrosis and life-threatening liver failure. If you have the following signs of liver disease, such as anorexia, jaundice, darkening of the urine, itching, tenderness of the abdomen, taking ciprofloxacin should be discontinued (see section "Side effect").

In patients receiving ciprofloxacin and those suffering liver disease, there may be a temporary increase in activity of "liver" transaminases, alkaline phosphatase or cholestatic jaundice (see section "Side effect"). Musculoskeletal system

Patients with severe myasthenia gravis should be used ciprofloxacin with caution, as possible exacerbation of symptoms.

When taking 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 rupture of the tendon can occur even a few months after cessation of ciprofloxacin treatment. In elderly patients and patients with diseases of tendons treated simultaneously with corticosteroids, there is an increased risk of tendonopathy.

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. Ciprofloxacin should be used with caution in patients with a history of indications of tendon diseases associated with the administration of quinolones.

Nervous system

Ciprofloxacin, like other fluoroquinolones, can provoke convulsions and reduce the threshold of convulsive readiness. Patients with epilepsy and advanced CNS diseases (eg, lowering the threshold of convulsive readiness, convulsive seizures in the history, cerebrovascular disorders, organic brain lesions or stroke) due to the threat of developing side effects from the CNS ciprofloxacin should be used only in those cases when the expected clinical effect exceeds the possible risk of side effects of the drug.

When ciprofloxacin was used, cases of development of epileptic status were reported (see section "Side effect"). In case of seizures, the drug should be discontinued. Mental reactions may occur even after the first use of fluoroquinolones, including ciprofloxacin. In rare cases, depression or psychotic reactions can progress to suicidal thoughts and self-damaging behavior, such as suicide attempts, including those committed (see "Side effect"). If a patient develops one of these reactions, stop taking ciprofloxacin and tell the doctor about it.

In patients taking fluoroquinolones, including ciprofloxacin, there were cases of sensory or sensorimotor polyneuropathy, gyneesthesia, dysesthesia, or weakness. If symptoms such as pain, burning, tingling, numbness, weakness occur, patients should inform the doctor about this before continuing the use of the drug.

Skin covers

When taking ciprofloxacin, a photosensitization reaction may occur, so patients should avoid contact with direct sunlight and ultraviolet light. Treatment should be discontinued if symptoms of photosensitivity are observed (for example, skin changes resemble sunburn) (see section "Side effect").

Cytochrome P450

It is known that ciprofloxacin is a moderate inhibitor of isoenzyme CYP 450 IA2. Caution should be exercised when using ciprofloxacin and preparations metabolized by these enzymes, such as theophylline, methylxanthine, caffeine, duloxetine, ropinirole, clozapine, olanzapine , etc., since an increase in the concentration of these drugs in the blood serum, caused by the inhibition of their metabolism by ciprofloxacin, can cause specific unwanted reactions.

Local Reactions

With intravenous administration of ciprofloxacin, a local inflammatory reaction may occur at the site of the drug (swelling, pain). This reaction is more common if the infusion time is 30 minutes or less.The reaction quickly passes after the end of the infusion and is not a contraindication for the subsequent administration of the drug, unless its course becomes complicated.

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. With simultaneous intravenous administration of ciprofloxacin and preparations for general anesthesia from the group of barbituric acid derivatives, continuous monitoring of the heart rate, blood pressure, and electrocardiogram is necessary.

In conditions in vitro ciprofloxacin may interfere with bacteriological research Mycobacterium tuberculosis, suppressing its growth, which can lead to false-negative results in the diagnosis of this pathogen in patients taking ciprofloxacin.

Content NaCl

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.

Form release / dosage:Solution for infusions 2 mg / ml.

Packaging:

100 ml in polyethylene bottles with welded caps.

Each bottle is placed in a pack of cardboard along with instructions for use.

10, 24, 48, 96 bottles, together with an equal number of instructions for use, are placed in a cardboard box (for hospitals).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004273

Date of registration:28.04.2017

Expiration Date:28.04.2022

The owner of the registration certificate:Pharma International Company Russia-CIS, LLCPharma International Company Russia-CIS, LLC

Manufacturer: & nbsp

Pharma International Company Russia-CIS, LLC Russia

Information update date: & nbsp02.06.2017

Illustrated instructions

Instructions

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