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

Excipients: cellulose microcrystalline 17.6 mg and 35.2 mg, sodium carboxymethyl starch (primogel) 19.0 mg and 38.0 mg, crospovidone (polyplasdone X El) 9.3 mg and 18.6 mg, povidone (polyvinylpyrrolidone) 19.0 mg and 38.0 mg, magnesium stearate 3.8 mg and 7.6 mg, silicon dioxide colloid 3.8 mg and 7.6 mg.

Weight of the tablet without a cover: 380 mg and 760 mg.

Shell composition:

Excipients: Hypromellose (hydroxypropylmethylcellulose) 4.26 mg and 8.52 mg, polysorbate (tween 80) 0.927 mg and 1.854 mg, povidone (polyvinylpyrrolidone) 2.666 mg and 5.332 mg, talc 1.22 mg and 2.44 mg, titanium dioxide 0.927 mg and 1.854 mg.

Weight of the coated tablet: 390 mg and 780 mg.

Description:

The tablets covered with a film membrane white or white with a yellowish shade of color, round, biconcave form. On the cross-section, two layers are visible, the inner layer of white with a yellowish hue of color.

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 in the case Pseudomonas aeruginosa) and / or activation of excretion from the microbial cell (efflux). The development of resistance due to the Qnr-encoding gene localized on plasmids has been reported.

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 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
Staphylococcus¹spp.	≤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. - 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 ofloxacin and thus belongs to the category of microorganisms with intermediate sensitivity.

3. Strains with a MIC value greater than 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. until 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.

4. Boundary 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 values for MIC (mg / l) and for diffusion testing (mm) using discs

Microorganism	Sensitive	Intermediate	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
	>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.	<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	<0,03^e	>0,12^e
Neisseria meningitidis	>35^f	33-34^f	<32^f
Bacillus anthracis Yersinia pestis	<0,25^a	-	-
Francisella tularensis	<0,5³	-	-

a. This reproducible standard is applicable only to dilutions with broth using cationic corrected 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 discs using air 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 ± 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 for 20-24 hours.

e. This reproducible standard applies only to dilutions with broth using cationic corrected 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 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 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 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.

A varying degree of sensitivity to ciprofloxacin for the following microorganisms was demonstrated: Acinetobacter baumannii, 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 monocytogenes, Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (with the exception of Mobiluncus spp., Peptostreptococcus spp., Propionibacterium acnes).

Pharmacokinetics:

Suction

After oral administration ciprofloxacin quickly absorbed mainly in the small intestine. The maximum concentration of ciprofloxacin in the blood serum is achieved after 1-2 hours. Bioavailability is about 70-80%. The values of the maximum concentration in blood plasma (C_max) and the area under the concentration-time curve (AUC) increase in proportion to the dose.

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), sulphociprofloxacin (M2), oxocycloploxacin (M3), formyl ciprofloxacin (M4), three of which (M1-M3) show antibacterial activity in vitro, comparable with antibacterial activity nalidixic acid. The antibacterial activity in vitro of the M4 metabolite, which is present in a smaller amount, corresponds more 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.

Indications:

Uncomplicated and complicated infections caused by susceptible to ciprofloxacin microorganisms.

Adults

- ANDrespiratory tract infection. 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 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;

- kidney and / or urinary tract infections;

- infection of the genitals, including adnexitis, gonorrhea, prostatitis;

- 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);

- prevention of invasive infections caused by Neisseria meningitides;

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 excipients, as well as other drugs from the group of fluoroquinolones;

- Pregnancy;

- lactation period;

- Children's and adolescence (up to 18 years - until 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 pulmonary form of anthrax);

- simultaneous reception of tizanidine (risk of pronounced reduction in blood pressure, drowsiness).

Carefully:

Severe atherosclerosis of cerebral vessels; impaired cerebral circulation; mental illness (depression, psychosis); epileptic syndrome, epilepsy; organic brain damage or stroke, lowering the threshold of convulsive readiness (or convulsive fits in the anamnesis), marked renal and / or hepatic insufficiency; elderly age; 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 QT, 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 CYP4501A2, (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine), myasthenia gravis gravis, deficiency of glucose-6-phosphate dehydrogenase.

Dosing and Administration:

Tablets should be taken orally, regardless of food intake, without chewing, squeezed with a small amount of liquid.

If the drug is used on an empty stomach, the active substance is absorbed more quickly. In this case, the tablets should not be washed down with milk products or beverages fortified with calcium (for example, milk, yogurt, juices with high calcium content). Calcium, contained in normal foods, does not affect the absorption of ciprofloxacin.

If, due to the severity of the condition or for other reasons, the patient is deprived of the ability to take the pill, it is recommended that parenteral therapy be given with an infusion solution of ciprofloxacin, and after the improvement of the condition, switch to the tablet form.

In the absence of other prescriptions, the following dosing regimen is recommended:

Adults

Table 1. The recommended daily dose of the drug Vero-ciprofloxacin, tablets, film coated, 250 mg, 500 mg

Indications	The daily dose of ciprofloxacin (mg)
Respiratory tract infections (depending on the severity of the infection and the patient's condition)	from 2 x 500 mg to 2 x 750 mg
Infections of the genitourinary system:
- acute, uncomplicated	from 2 x 250 mg to 2 x 500 mg
- Cystitis in women (before menopause)	1 x 500 mg
- complicated	from 2 x 500 mg to 2 x 750 mg
- adnexitis, prostatitis, orchitis, epididymitis	from 2 x 500 mg to 2 x 750 mg
Gonorrhea	1 x 500 mg
- extragenital
- acute, uncomplicated
Diarrhea	2 x 500 mg
Other infections (see section "Indications for use")	2 x 500 mg
Particularly difficult, representing a threat to life, incl.
- streptococcal pneumonia
- recurrent infections in cystic fibrosis of the lungs
- infections of bones and joints	2 x 750 mg
- septicemia
- peritonitis
Especially when available Pseudomonas, Staphylococcus or Streptococcus
Pulmonary form of anthrax (treatment and prevention)	2 x 500 mg
Prevention of invasive infections caused by Neisseria meningitidis	1 x 500 mg

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 rate.

Children and teens

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

Table 2. Recommended daily dose of the drug Vero-ciprofloxacin, film-coated tablets, 250 mg, 500 mg in children

Indications

The daily dose of ciprofloxacin (mg)

Infections in fibrinokistoznoy degeneration (cystic fibrosis)

2 x 20 mg / kg body weight

(maximum dose of 750 mg)

Pulmonary form of anthrax (postexposure)

2 x 15 mg / kg body weight

(maximum dose of 500 mg)

Dosage regimen for pulmonary form of anthrax (treatment and prevention) - see Table 1 and Table 2.

The drug should be taken immediately after a suspected or confirmed infection. The total duration of taking ciprofloxacin in the pulmonary form of anthrax is 60 days.

The dosing regimen for violations of kidney or liver function in adults

Table 3. Recommended doses for patients with renal insufficiency

Creatinine clearance

(ml / min / 1.73 m²)

Plasma Creatinine

(mg / 100 ml)

The maximum daily dose of ciprofloxacin for oral administration

from 30 to 60

from 1.4 to 1.9

Maximum 1000 mg

below 30

>2,0

Maximum 500 mg

Patients with renal failure on hemodialysis

1. With a clearance of creatinine from 30 to 60 ml / min / 1.73 m² (moderate renal insufficiency) or its concentration in blood plasma from 1.4 to 1.9 mg / 100 ml, the maximum oral dose of ciprofloxacin should be 1000 mg per day.

2. With a creatinine clearance of 30 ml / min / 1.73 m² and less (severe renal insufficiency) or its plasma concentration from 2 mg / 100 ml or more, the maximum oral dose of ciprofloxacin should be 500 mg per day. In days of hemodialysis ciprofloxacin take after the procedure.

Out-patient patients with renal failure who are on continuous peritoneal dialysis

The maximum daily dose of ciprofloxacin should be 500 mg (1 tablet of the drug Vero-ciprofloxacin for 500 mg or 2 tablets of the drug Vero-Ciprofloxacin 250 mg each).

Patients with hepatic insufficiency

Correction of the dose is not required.

Patients with renal and hepatic insufficiency

The dosing regimen is similar to that described in the subsection "Patients with renal insufficiency on hemodialysis".

Children with kidney failure and / or impaired liver function

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

Duration of therapy

The duration of treatment depends on the severity of the disease, clinical and bacteriological control. It is important to continue treatment systematically, at least 3 days after the disappearance of fever or other clinical symptoms.

Average duration of treatment:

- 1 day with acute uncomplicated gonorrhea and cystitis;

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

- the entire neutropenia period in immunocompromised patients;

- no more than 2 months with osteomyelitis;

- from 7 to 14 days with other infections.

In infections caused by Streptococcus spp., Due to the risk 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.

Side effects:

The undesirable reactions listed below were classified as follows: "very often" (≥10), "often" (from ≥1 / 100 to <1/10), "infrequently" (from ≥1 / 1000 to <1/100), " rarely "(from ≥1 / 10000 to <1/1000)," very rarely "(<10000)," frequency is unknown ". Unwanted reactions, which were recorded only during post-marketing observations, and whose frequency was not evaluated, are designated "unknown".

Often (≥1/100 - <1/10)	Infrequently (≥1/1000 - <1/100)	Rarely (≥1/10000 - <1/1000)	Rarely (<10000)	Frequency unknown
Infectious and parasitic diseases
	Mycotic superinfection	Pseudomembranous colitis (in very rare cases with possible fatal outcome
On the part of the hematopoiesis system
	Eosinophilia	Leukopenia Anemia Neutropenia, Leukocytosis Thrombocytopenia Thrombocytosis	Hemolytic anemia Agranulocytosis Pancytopenia (life threatening) Bone marrow depression (life threatening)
From the immune system
		Allergic reactions Allergic edema/ Angioedema	Anaphylactic reactions Anaphylactic shock (life threatening) Whey disease
From the side of metabolism and nutrition
	Decreased appetite and intake of food	Hyperglycaemia Hypoglycaemia
Mental disorders
	Psychomotor hyperactivity / Agitation	Confusion and disorientation Anxiety Disturbance of dreams (nightmares) Depression (increased behavior for damage, such as suicidal behavior / thoughts, as well as attempted suicide or suicide) Hallucinations	Psychotic reactions (increased behavior for self-harm, such as suicidal acts / thoughts, as well as attempted suicide or suicide)
From the central nervous system
	Headache Dizziness Sleep disturbance	Paresthesia and dysesthesia Hyperesthesia Tremor Seizures, including epileptic seizures Vertigo	Migraine Violation of coordination movements Impaired smell Hyperesthesia Intracranial hypertension (cerebral pseudotumorous symptomatology)	Peripheral neuropathy and polyneuropathy
From the side of the organ of vision
		Disorders view	Violation color perceptions
From the side of the hearing organ and labyrinthine disorders
		Noise in ears Hearing Loss	Hearing Impairment
From the heart
		Tachycardia		Interval lengthening QT Ventricular arrhythmias (including the "pirouette" type) *
From the side of the vessels
		Vasodilation Decrease arterial pressures Feeling "tide" of blood to face	Vasculitis
From the respiratory system, organs of the chest and mediastinum
		Disturbance of breathing (including bronchospasm)
Co side of the gastrointestinal tract
Nausea Diarrhea	Vomiting Abdominal pain Dyspepsia Flatulence		Pancreatitis
Co sides of the liver and bile ducts
	Increase activity "hepatic" transaminase Increase concentrations bilirubin	Impaired liver function Jaundice Hepatitis (non-infectious)	Necrosis of liver tissue (in extremely rare cases progressing to life-threatening liver failure)
From the skin and subcutaneous tissues
	Rash Itching Hives	Photocibilization 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 connective and muscular tissue
	Arthralgia Musculoskeletal pain (including pain in the limbs, back pain, chest pain)	Myalgia Arthritis Increase muscular tone Muscular convulsions	Muscle weakness Tendonitis Rupture of tendons (mainly Achilles) Exacerbation symptoms myasthenia gravis
Co hand kidney and urinary tract
	Impaired renal function	Renal insufficiency Hematuria Tubulointerstitial nephritis
General disorders and disorders at the site of administration
Reactions in place injections	Pain syndrome nonspecific etiology General malaise Fever	Edema Sweating (hyperhidrosis)	Violation of gait
Laboratory indicators
	Increased activity of alkaline phosphatase in the blood	Change content prothrombin Increase activity amylase		Increase INR (in patients receiving vitamin K antagonists)

* more often in patients who are predisposed to developing an extension of the QT interval.

The frequency of development of the following adverse reactions with the use of stepwise therapy with ciprofloxacin (with intravenous administration of the drug followed by oral administration) is higher than with oral administration:

Often	Vomiting, increased activity of "liver" transaminases, rash
Infrequently	Thrombocytopenia, thrombocytosis, confusion and disorientation, hallucinations, paresthesia and dysesthesia, convulsions, vertigo, visual impairment, hearing loss, tachycardia, vasodilation, lowering blood pressure, reversible liver function disorders, jaundice, kidney failure, edema.
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:

In the case of an overdose with oral administration in several cases, a reversible toxic effect on the renal parenchyma was noted.Therefore, in case of an overdose, in addition to standard measures (gastric lavage, after which it is necessary to take Activated carbon, the introduction of a large amount of fluid, the creation of an acidic urine reaction to prevent crystalluria), it is also recommended to monitor the kidney function and take magnesium and calcium-containing antacids, which reduce the absorption of ciprofloxacin. With the help of hemo- or peritoneal dialysis, only a small amount of ciprofloxacin (less than 10%) is excreted.

Interaction:

Drugs that cause lengthening intervals QT

Caution should be exercised while using ciprofloxacin, as well as other fluoroquinolones, for patients receiving medications that cause lengthening of the interval QT (for example, antiarrhythmic drugs of Class I A or Class III, tricyclic antidepressants, macrolides, antipsychotics), (see section "Special instructions").

Formation of chelate compounds

Simultaneous administration of tablet forms of ciprofloxacin and cation-containing preparations, mineral supplements containing calcium, magnesium, aluminum, iron, sucralfate, antacids, polymeric phosphate compounds (such as sevelamer, lanthanum carbonate) and preparations with a large buffer capacity (such as didanosine tablets) containing magnesium, aluminum or calcium, reduces the absorption of ciprofloxacin. In such cases ciprofloxacin should be taken either 1-2 hours before or 4 hours after taking these drugs.

This restriction does not apply to drugs belonging to the class of blockers H₂-gistaminovyh receptors.

Eating and dairy products

The simultaneous use of ciprofloxacin and dairy products or beverages enriched with minerals (eg milk, yogurt, calcium-fortified orange juice) should be avoided, since the absorption of ciprofloxacin may decrease. However, calcium, which is part of other foods, does not significantly affect the absorption of ciprofloxacin.

Omeprazole

When combined use of ciprofloxacin and drugs containing omeprazole, there may be a slight decrease in the maximum plasma concentration in the plasma and a decrease in the area under the "concentration-time" pharmacokinetic curve.

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 simultaneous application of these two drugs is unavoidable, it is recommended to conduct constant monitoring of the concentration of theophylline in the blood plasma and, if necessary, reduce the dose of theophylline (see section "Special instructions", Cytochrome P450).

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.

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 sulfanylurea (glibenclamide, glimepiride), the development of hypoglycemia is presumably due to an increase in the effect of oral hypoglycemic agents (see the "Side effect" section).

Probenecid

Probenecid slows the rate of excretion of ciprofloxacin by the kidneys. The simultaneous use of preparations containing probenecid and ciprofloxacin increases the concentration of ciprofloxacin in the blood plasma.

Phenytoin

With the simultaneous use of ciprofloxacin and phenytoin, there was an increase or decrease in the content of phenytoin in the blood plasma. In order to avoid weakening of the anticonvulsant effect of phenytoin due to a decrease in its concentration, 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 content of phenytoin in the blood plasma during the entire period of simultaneous application of both drugs and for a short time after the completion of the combination therapy.

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 simultaneous therapy with methotrexate and ciprofloxacin, careful monitoring should 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) by 7 times (from 4 to 21 times), an increase in the indicator "area under the concentration-time curve" (AUC) - 10 times (from 6 to 24 times). An increase in the concentration of tizanidine in the blood serum can cause a decrease in blood pressure and drowsiness.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 C_mOh 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 rittinirol and ciprofloxacin, a moderate isoenzyme inhibitor CYP450 1A2, leads to an increase in C_mOh 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 1A2, leads to a decrease in lidocaine clearance by 22% when administered intravenously. Despite the good tolerability of lidocaine, simultaneous application with ciprofloxacin may increase the side effects due to interaction (see section "Special instructions", Cytochrome P450).

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. The patient's condition should be monitored and, if necessary, corrected for the dosage regimen of clozapine during its simultaneous use with ciprofloxacin and for a short time after completion of the combination therapy (see section "Specific guidance", Cytochrome P450).

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 C_max and AUC 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 pneumoniae

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

Infections of the genitourinary system

When treating patients with epididymoortitis and pelvic inflammatory diseases, it should be borne in mind that these infections can be caused by strains Neisseria gonorrhoeae, resistant to fluoroquinolones. The empirical use of ciprofloxacin for the treatment of such patients is possible only 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. In the appointment of ciprofloxacin, patients with urinary tract infections should take into account 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 in the treatment of patients with postoperative infections of the abdominal cavity are limited.

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.

Infections of bones and joints

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

Pulmonary form of anthrax

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

Resistance

During or 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.

Application of the drug 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 complications of cystic fibrosis (in children from 5 to 17 years) 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.

Hypersensitivity

Sometimes after the first dose of the drug may develop a hypersensitivity to the drug, including allergic reactions, which should be reported immediately to the doctor in charge.In rare cases, after the first application, anaphylactic reactions may occur up to anaphylactic shock. In these cases, the drug should be discontinued immediately and treated accordingly.

Hypoglycaemia

As with the use of other fluoroquinolones, the use of ciprofloxacin may 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.

Deficiency of glucose-6-phosphate dehydrohease (G-6-FDH)

In patients with deficiency of G-6-FDH receiving 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.

Visual disturbances

In case of signs of visual impairment or any other side effects on the part of the eye, consult an ophthalmologist.

Nervous system

Vero-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 anamnesis, cerebral circulatory disorders, organic brain lesions or stroke), in connection with the threat of the development of adverse reactions from the CNS, Vero-Ciprofloxacin should be used only then , 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 Vero-Ciprofloxacin. In rare cases, depression or psychotic reactions can progress to suicidal thoughts and suicidal attempts, including those that have been completed (see "Side effect"). If a patient develops one of these reactions, stop taking the medication and tell the doctor about it.

Patients taking fhorhinolony noted cases of sensory or sensorimotor polyneuropathy, hypoesthesia, dysesthesia, or weakness. If symptoms such as pain, burning, tingling, numbness, weakness occur, the patient should be informed by the doctor before continuing the use of the drug.

Skin covers

During the treatment with Vero-Ciprofloxacin, ultraviolet irradiation should be avoided (including contact with direct sunlight). Treatment with the drug should be discontinued if symptoms of photosensitivity are observed (for example, skin changes resemble sunburn).

Heart Disease

Ciprofloxacin has an effect on lengthening 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; ciprofloxacin Use with caution in combination with drugs that extend the interval QT (for example, antiarrhythmic drugs classes IA and III, tricyclic antidepressants, macrolides, neuroleptics),in patients with an 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)). In elderly patients there is an increased sensitivity to the action of drugs that cause lengthening of the interval QT.

Gastrointestinal tract

If severe or prolonged diarrhea occurs during or after treatment with Vero-Ciprofloxacin, the diagnosis of pseudomembranous colitis should be ruled out, which requires immediate discontinuation of the drug and the appointment of appropriate treatment. Contraindicated in the use of drugs that suppress the intestinal peristalsis.

Hepatobiliary system

When ciprofloxacin was used, cases of liver necrosis and life-threatening liver failure were noted, in the presence of symptoms of liver disease, such as anorexia, jaundice, darkening of the urine, itching, abdominal tenderness, ciprofloxacin should be discontinued. In patients taking the drug and undergoing liver disease,there may be a temporary increase in the activity of "hepatic" transaminases and alkaline phosphatase or cholestatic jaundice.

Musculoskeletal system

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

When ciprofloxacin is used, cases of tendinitis and rupture of tendons (predominantly Achilles tendon), sometimes bilateral, within the first 48 hours after initiation of therapy, tendonitis and tendon rupture may occur even a few months after discontinuation of ciprofloxacin treatment, in elderly patients and patients with diseases of the tendons, simultaneously receiving treatment with glucocorticosteroids, there is an increased risk of tendonopathy; if pain occurs in tendons or when the first signs of tendovaginitis appear, treatment should be discontinued due to the fact that individual cases of inflammation and even rupture of tendons during treatment with fluoroquinolones are described. At the first signs of tendonitis, it is necessary to exclude physical activity, as well as consult a doctor. Ciprofloxacin should be used with caution in patients with a history of indications of tendon diseases associated with the intake of fluoroquinolones.

Cytochrome P450

Caution should be exercised with the simultaneous use of ciprofloxacin and drugs metabolized by isoenzymes CYP450 1A2, such as ropinirole, olanzapine, tizanidine, theophylline, methylxanthine, caffeine, duloxetine, clozapine.

An increase in the concentration of these drugs in the blood serum, caused by the inhibition of their metabolism by ciprofloxacin, can cause specific undesirable reactions.

In order to avoid the development of crystalluria, an increase in the recommended daily dose is unacceptable, and during the treatment with Vero-Ciprofloxacin it is necessary to provide a sufficient amount of fluid while observing normal diuresis and maintaining an acidic urine reaction. 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 development of crystalluria were reported.

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 the drug Vero-Ciprofloxacin.

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

Patients taking Vero-Ciprofloxacin should be careful when driving a car and engaging in other potentially dangerous activities that require increased attention and speed of psychomotor reactions (especially when using ethanol at the same time).

Form release / dosage:

Film coated tablets, 250 mg and 500 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10 tablets in a jar or a bottle of polymer materials.

Each jar or vial, or 1 circuit cell pack together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 30 ° C.

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:P N002328 / 01

Date of registration:24.04.2008 / 16.09.2015

Expiration Date:Unlimited

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Representation: & nbspVEROPHARM, AO VEROPHARM, AO Russia

Information update date: & nbsp05.03.2017

Illustrated instructions

Instructions

Vero-Ciprofloxacin (Vero-Ciprofloxacin)