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

Each 50 ml bottle contains 100 mg of ciprofloxacin as an active ingredient. Each 100 ml bottle contains 200 mg of ciprofloxacin as an active ingredient. Excipients: lactic acid 20%, sodium chloride, hydrochloric acid 1N, water for injection.

Description:

Transparent from a colorless to slightly yellowish solution.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

Ciprofloxacin is a synthetic antibacterial agent of a broad spectrum of action 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 carried out 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.

In Vitro Sensitivity Testing

The reproducible criteria for testing susceptibility 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 meningitidis	≤0,03	>0,06
Boundary values not associated with microbial species⁴	≤0,5	>1

1. Staphylococcus spp. - borderline values for ciprofloxacin and ofloxacin 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 exceeding the sensitive / moderately sensitive threshold 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 H. Influenzae, no.

4. Boundary values that are not related to 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 ciprofloxacin are presented in the table below.

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

Microorganism	Sensitive	Intermediate	Resistant
Enterobacteriaceae	<1^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
	>21^b	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^a	2^a	>4^a
Enterococcus spp.	>21^b	16-20^b	<15^b
Haemophilus spp.	<1в	--	--
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 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^z	--	--

a. This reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (CAMHB) which is incubated with air access at a temperature of 35 ± 2 ° C for 16-20 hours for strains Enterobacteriaceae, Pseudomonas aeruginosa, other bacteria not belonging to the E familynterobacteriaceae, Staphylococcus spp., Enterococcus spp. and Bacillus anthracis; 20-24 hours for Acinetobacter spp., 24 hours 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 incubated with air access at a temperature of 35 ° C ± 2 ° C for 20-24 hours.

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

etc. 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 ° C ± 1 ° C (not exceeding 37 ° C) in 5% CO2 for 20-24 hours.

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

f.This reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (CAMHB) 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

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 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, Pasteurella spp., Francisella tularensi, 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.

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

It is believed that the natural resistance to ciprofloxacin possess Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enteroccus faecium, Listeria monocytogene Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (with the exception of Mobiluncus spp., Peptostreptococus spp., Propionibacterium acnes).

Pharmacokinetics:

Suction

After iv introduction C_max ciprofloxacin 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, four metabolites of ciprofloxacin can be detected in small concentrations: diethylciprofloxacin (M1), sulphociprofloxacin (M2), oxocycloploxacin (M3), formyl ciprofloxacin (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. 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 values of the maximum concentration in the blood plasma (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 in children 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 catarrhalis, Legionella spp. and staphylococci,

- infections of the middle ear (otitis media), adnexal sinuses (sinusitis), especially if these infections are caused by gram-negative microorganisms, including Pseudomonas aeruginosa or staphylococci,

- eye infections,

- infection of the kidney and / or urinary tract,

- infections of the genitals, including adnexitis, gonorrhea, prostatitis,

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

- skin and soft tissue infections,

- 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 drugs from the group of fluoroquinolones, as well as to auxiliary substances (see section "Composition").

Simultaneous use of ciprofloxacin and tizanidine due to clinically significant side effects (hypotension, drowsiness) associated with an increase in the concentration of tizanidine in the blood plasma (see section "Interactions with other drugs").

Carefully:

Use in children

Ciprofloxacin is not recommended for use in children under 18 years of age for the treatment of other infectious diseases, except for the treatment of complications of cystic fibrosis of the lungs (in children aged 5 to 17 years) caused by Pseudomonas aeruginosa, and for the treatment and prevention of the pulmonary form of anthrax (after suspected or proven infection Bacillus anthracis).

The use of ciprofloxacin in children should be initiated only after an assessment of the benefit / risk ratio due to possible side effects on the joints and tendons.

Pregnancy and lactation:

The safety of ciprofloxacin in pregnant women has not been established. However, based on the results of animal studies, the likelihood of adverse effects on the joints of the newborns can not be completely ruled out, in this connection ciprofloxacin should not be given to pregnant women.

At the same time, in the course of studies on animals teratogenic action (malformations) was not established.

Ciprofloxacin is excreted in breast milk. Because of the potential risk of damage to the articular cartilage of newborns, ciprofloxacin should not be prescribed to nursing women.

Dosing and Administration:

Adults

In the absence of other prescriptions, the following dosing regimen should be followed:

Table 1. Recommended daily dose of Ciprobay®, infusion solution, in adults

Indications	Single dose for adults, taking into account the frequency of administration per day (ciprofloxacin, mg, intravenous administration)
Respiratory tract infections (depending on the severity of the infection and the patient's condition)	From 400 mg x 2 times a day to 400 mg x 3 times a day
Infections of the genitourinary system: - acute, uncomplicated - complicated - adnexitis, prostatitis, orchitis, epididymitis	From 200 mg x 2 times a day to 400 mg x 2 times a day From 400 mg x 2 times a day to 400 mg x 3 times a day From 400 mg x 2 times to 400 mg x 3 times a day
Diarrhea	400 mg x 2 times a day
Other infections (see section "Indications for use")	400 mg x 2 times a day
Particularly serious infections that pose a threat to life, especially if 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 x 3 times a day
Pulmonary form of anthrax (treatment and prevention)	400 mg x 2 times a day (adults)

Children and teenagers.

Table 2. Recommended daily dose of Ciprobay®, infusion solution, in children and adolescents

Indication

Single dose for children and adolescents, taking into account the frequency of administration per day (ciprofloxacin, mg, intravenous administration)

Infections in cystic fibrosis

10 mg / kg body weight x 3 times a day (maximum dose of 400 mg)

Pulmonary form of anthrax (postcontact)

10 mg / kg body weight x 2 times a day (maximum dose of 400 mg)

Use in selected patient groups

Dosing regimen in elderly patients (after 65 years)

Elderly patients should be prescribed lower doses of ciprofloxacin, depending on the severity of the disease and the creatinine clearance (see also information on patients with impaired hepatic and / or renal function).

Dosage regimen for pulmonary form of anthrax (treatment and prevention) for adults and children

See the information in Tables 1 and 2.

Treatment should begin immediately after suspected or confirmed infection.

The total duration of treatment with ciprofloxacin in pulmonary form of anthrax is 60 days.

Dosing regimen for violations of kidney and liver function in adults

Table 3. Recommended doses for patients with renal insufficiency

Creatinine clearance [ml / min 1.73 m2]

Serum creatinine [mg / 100 ml]

Total daily dose of the drug Ciprobai ® solution for infusions

30 to 60

1.4 to 1.9

Maximum 800 mg

Below 30

>2,0

Maximum 400 mg

Dosing regimen for renal dysfunction in patients on hemodialysis

- with a clearance of creatinine from 30 to 60 ml / min / 1.73 m2 or its concentration in the blood plasma from 1.4 to 1.9 mg / 100 ml, the maximum dose of Ciprobay® should be 800 mg per day;

- with a creatinine clearance of 30 ml / min / 1.73 m2 or less (severe renal failure) or a plasma concentration of 2 mg / 100 ml or more, the maximum dose of Ciprobay® should be 400 mg per day on dialysis days after the procedure.

Dosing regimen in patients with renal failure with prolonged outpatient peritoneal dialysis (CAPD)

The drug Ciprobay® is added to dialysate (intraperitoneally): 50 mg of ciprofloxacin per liter of dialysate is administered 4 times a day every 6 hours.

Dosing regimen in patients with hepatic insufficiency

Correction of the dose is not required.

Dosing regimen in patients with impaired renal or hepatic function

- at creatinine clearance from 30 to 60 ml / min / 1.73 m2 (moderate renal failure) or at a plasma creatinine concentration of 1.4 to 1.9 mg / 100 ml, the maximum daily dose of the drug Ciprobay® should be 800 mg;

- with creatinine clearance of 30 ml / min / 1.73 m2 or less (severe renal failure) or with a creatinine concentration in the blood plasma of 2 mg / 100 ml or more, the maximum daily dose of the drug Ciprobay® should be 400 mg.

Dosage regimen for violations of kidney or liver function in children

The dosage regimen in children with impaired renal and hepatic functions has not been studied.

Mode of application

The drug Ciprobay® is administered as an intravenous infusion lasting at least 60 minutes.The infusion solution should be injected slowly into a large vein, which will prevent complications at the site of infusion. The infusion solution can be administered alone or together with other compatible infusion solutions.

Compatibility with other solutions

Infusion solution of the preparation Ciprobay® is compatible with 0.9% sodium chloride solution, Ringer's solution, Ringer's lactate solution, 5% and 10% dextrose solution, 10% fructose solution, and 5% dextrose solution with 0.225% NaCl or 0.45% NaCl . The solution obtained after mixing the preparation Ciprobai® 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 Ciprobay® should be administered separately. Visible signs of incompatibility are precipitation, clouding or discoloration of the solution.

Incompatibilities occur with all solutions / preparations that are physically or chemically unstable at the pH of the Ciprobay® infusion solution (for example,penicillins, heparin solutions), and in particular with solutions that change the pH value to the alkaline side (the pH of the infusion solution of the preparation Ciprobay® is 3.9-4.5).

Solution for infusion Ciprobay® is light-sensitive, so the vial should be removed from the box only before use. In direct sunlight, the guaranteed stability of the solution is 3 days.

When storing the Ciprobay® infusion solution 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 lid in the area of the central ring.

Piercing outside the center ring can cause damage to the cover.

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. It is important to continue treatment for at least 3 days after the disappearance of fever or other clinical symptoms. Average duration of treatment:

Adults

- 1 day with acute uncomplicated gonorrhea,

- up to 7 days with infections of the kidneys, urinary tract, abdominal organs,

- the entire neutropenia period in patients with weakened immunity,

- no more than 2 months with osteomyelitis,

- 7 to 14 days with other infections.

In infections caused by Streptococcus spp., because of the risk of late complications, treatment should last at least 10 days.

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

Children and teens

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

Side effects:

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

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

Often ≥1% - <10%	Infrequently ≥0,1% - <1%	Rarely ≥0,01% - <0,1%	Rarely <0,01%	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	Hyperglycemia Hypoglycaemia
MENTAL DISORDERS
	Psychomotor hyperactivity / agitation	Confusion and disorientation Anxiety Dream disturbance (nightmares) Depression (which can lead to self-harm in behavior such as suicidal behavior / thoughts, as well as suicide attempt or suicide) Hallucinations	Psychotic reactions (which can lead to self-damaging behavior, such as suicidal behavior / thoughts, as well as attempted suicide or failed suicide)
FROM THE SIDE OF THE CENTRAL NERVOUS SYSTEM
	Headache Vertigo Disturbance of sleep Disturbance of taste	Paresthesia and Dysesthesia Hypesesthesia Tremor Seizures (including epileptic seizures) Vertigo	Migraine Disturbance of coordination of movements Disturbance of 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 prolongation Ventricular arrhythmias (including pirouette type) *
FROM THE SIDE OF VESSELS
		Vasodilatation Reduction of blood pressure Feeling of "tidal" blood to face	Vasculitis
FROM THE SIDE OF THE RESPIRATORY SYSTEM, BODY CIRCULAR AND MEDIUM BODY ORGANS
		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 "hepatic" transaminases Increase in 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 Urticaria	Photosensitivity Blistering	Petechia Erythema multiforme 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 insufficiency, hematuria Crystalluria Tubulointerstitial nephritis
GENERAL DISTURBANCES AND VIOLATIONS IN THE SITE OF INTRODUCTION
Reactions at the site of administration	Pain syndrome of nonspecific etiology General malaise Fever	Sweat Sweating (hyperhidrosis)	Violation of gait
LABORATORY INDICES
	Increased activity of alkaline phosphatase in the blood	Change in prothrombin content Increase in amylase activity		Increase INR (in patients receiving vitamin K antagonists)

* more often in patients who are predisposed to the development of prolongation of the QT interval (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:

It is necessary to carefully monitor the patient's condition, to carry out usual emergency measures, to ensure sufficient supply of fluid.In order to prevent the development of crystallaria, it is also recommended to monitor kidney function, including pH and acidity of urine. With the help of hemo- or peritoneal dialysis, only a small amount of ciprofloxacin (less than 10%) is excreted.

Interaction:

Medicinal products that cause prolongation of the QT interval

Caution should be exercised while using ciprofloxacin, as well as other fluoroquinolones, in patients receiving drugs that cause prolongation of the QT interval (for example, antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides and antipsychotics) (see "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, then it is recommended that the theophylline concentration in the blood plasma be monitored continuously and, if necessary, the dose of theophylline lowered.

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 the blood plasma: an increase in the maximum concentration (C_max) in 7 times (from 4 to 21 times), the 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

Clinical studies have shown that the simultaneous use of duloxetine and potent inhibitors of the CYP450 1A2 isoenzyme (such as fluvoxamine) can lead to an increase in AUC and C_max duloxetine. 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 inhibitor of the isoenzyme CYP450 1A2, leads to an increase in C_max and AUC of 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 inhibitor of the isoenzyme CYP450 1A2, leads to a decrease in lidocaine clearance 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 ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg, there was an increase in C_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

In the treatment of severe infections caused by staphylococcus infections caused by anaerobic bacteria, Ciprobay® should be used in combination with appropriate antibacterial agents.

Infections due to Streptococcus pneumoniae

Ciprobay® is not recommended for the treatment of infections caused by Streptococcus pneumoniae, because of its insufficient effectiveness against the pathogen.

Infections of the reproductive tract

In genital infections presumably caused by strains Neisseria gonorrhoeae, resistant to fluoroquinolones, should take into account information on local resistance to ciprofloxacin and confirm the sensitivity of the causative agent in laboratory tests.

Heart Disease

The drug Ciprobay® has an effect on the elongation of the QT interval (see the "Side effect" section). Given that women have a larger average duration of the QT interval than men, they are more sensitive to drugs that cause prolongation of the QT interval. In elderly patients, there is also increased sensitivity to the action of drugs that cause prolongation of the QT interval. Therefore, use with caution the preparation Ciprobay ® in combination with drugs that extend the QT interval (for example, antiarrhythmic drugs of classes I A and III, tricyclic antidepressants, macrolides and antipsychotic drugs) (see.(See "Interactions with Other Drugs"), or in patients at increased risk of QT interval prolongation or pirouette-type arrhythmia (eg, congenital QT prolongation syndrome, unadjusted electrolyte imbalance, such as hypokalemia or hypomagnesemia, and with such heart diseases like heart failure, myocardial infarction, bradycardia).

Use in children

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 lung, there is no association between cartilage damage and joints with drug administration. It is not recommended to use Ciprobay® 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 and for the treatment and prevention of pulmonary forms of anthrax (after suspected or proven infection Bacillus anthracis).

Hypersensitivity

Sometimes after taking the first dose of Ciprobay®, hypersensitivity to the drug, including allergic reactions, may develop, 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 Ciprobay® should be stopped immediately and appropriate treatment should be given.

Gastrointestinal tract

If a severe and prolonged diarrhea occurs during or after treatment with Ciprobay®, the diagnosis of pseudomembranous colitis should be ruled out, which requires immediate discontinuation of the drug and the 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 using the drug Ciprobay®, cases of liver necrosis and life-threatening liver failure were noted. If you have the following signs of liver disease, such as anorexia, jaundice, darkening of the urine, itching, abdominal tenderness, taking Ziprobay® should be discontinued (see section "Side effect").

In patients taking Ziprobai® and having 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 treated with Ciprobay ® with caution, as possible exacerbation of symptoms.

When taking Ziprobay®, cases of tendinitis and rupture of tendons (predominantly Achilles tendon) may occur, sometimes bilateral, within the first 48 hours after initiation of therapy. Inflammation and rupture of the tendon can occur even a few months after discontinuation of treatment with Ciprobay®. 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), ciprofloxacin should be discontinued, physical activity should be avoided, there is a risk of rupture of the tendon, as well as consult a doctor.

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

Nervous system

Ciprobay ®, like other fluoroquinolones, can provoke cramps 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 anamnesis, cerebral circulation disorders, organic brain lesions or stroke) due to the threat of the development of adverse reactions from the CNS preparation Ziprobay ® should be used only in those cases , when the expected clinical effect exceeds the possible risk of side effects of the drug.

When using the drug Ciprobay®, 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 Ciprobay®. In rare cases, depression or psychotic reactions can progress to suicidal thoughts and self-damaging behavior, such as suicide attempts, including those that have occurred (see "Side effect").If a patient develops one of these reactions, stop taking Ziprobai® and inform the doctor about it.

In patients taking fluoroquinolones, including Ciprobay®, there have been cases of sensory or sensorimotor polyneuropathy, hypoesthesia, dysesthesia, or weakness. If symptoms such as pain, burning, tingling, numbness, weakness occur, patients should be informed by the doctor before continuing the use of the drug.

Skin covers

When taking Ziprobai®, a photosensitization reaction may occur, so patients should avoid contact with direct sunlight and UV 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 Ciprobay® is a moderate inhibitor of CYP 450 1A2 isoenzymes. Caution should be exercised when using the drug Ciprobay® and drugs metabolized by these enzymes, such as tizanidine, theophylline, methylxanthine, caffeine, duloxetine, ropinirole, clozapine, olanzapine and others, since an increase in the concentration of these drugs in the blood serum, due to the inhibition of their metabolism by ciprofloxacin, can cause specific undesirable reactions.

Local Reactions

With the intravenous administration of the drug Ciprobay®, there may be a local inflammatory reaction 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 heart rate, blood pressure, and ECG is necessary.

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 Ziprobay®.

NaCl content

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 consumption is limited (heart failure, renal 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 infusion 2 mg / ml 100 mg, 200 mg.

Packaging:Vials of colorless glass to 50 and 100 ml. One bottle with instructions for use in a cardboard box.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Do not store in the refrigerator. Do not freeze. Keep out of the reach of children.

Shelf life:4 years. Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013670 / 02

Date of registration:12.02.2008

Date of cancellation:2016-08-23

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER PHARMA, AG Germany

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp24.08.2016

Illustrated instructions

Instructions

Ciprobay® (Ciprobay®)