Instructions for use CIPROFLOXACIN

Description

Capsule-shaped tablets, with a biconvex surface, film-coated, white or almost white. White in cross section.

Pharmacotherapeutic group

Antimicrobial drugs are quinolone derivatives. Fluoroquinolones.

ATS code

J01MA02

Pharmacological properties

Pharmacokinetics

When taken orally, it is quickly and fairly completely absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Eating slows down absorption but does not change maximum concentration (Cmax) or bioavailability. Bioavailability - 50-85%, volume of distribution - 2-3.5 l/kg, binding to plasma proteins - 20-40%. The time to reach the maximum concentration (TCmax) is 60-90 minutes, the maximum concentration linearly depends on the dose taken and is 1.2, 2.4, 4.3 and 5.4 μg/ml at doses of 250, 500, 750 and 1000 mg, respectively. 12 hours after oral administration of 250, 500 and 750 mg, the concentration of the drug in plasma decreases to 0.1, 0.2 and 0.4 mcg/ml, respectively.

Well distributed in body tissues (excluding fat-rich tissue, such as nervous tissue). The concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gallbladder, bile, intestines, abdominal and pelvic organs (endometrium, fallopian tubes and ovaries, uterus), seminal fluid, prostate tissue, kidneys and urinary tract, pulmonary tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. It penetrates into the cerebrospinal fluid in a small amount, where its concentration in the absence of inflammation of the meninges is 6-10% of that in the blood serum, and in the case of inflammation - 14-37%. Ciprofloxacin also penetrates well into the ocular fluid, pleura, peritoneum, lymph, and through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in blood serum.

Metabolized in the liver (15-30%) with the formation of low-active metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

The half-life is about 4 hours, in case of chronic renal failure - up to 12 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (40-50%) and in the form of metabolites (15%), the rest - through the gastrointestinal tract. intestinal tract. A small amount is excreted in breast milk.

Renal clearance - 3-5 ml/min/kg; total clearance - 8-10 ml/min/kg.

In chronic renal failure (creatinine clearance above 20 ml/min), the percentage of the drug excreted through the kidneys decreases, but accumulation in the body does not occur due to a compensatory increase in drug metabolism and excretion through the gastrointestinal tract.

Pharmacodynamics

A broad-spectrum antimicrobial agent, a quinolone derivative, suppresses bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, growth and division of bacteria; causes pronounced morphological changes (including cell wall and membranes) and rapid death of the bacterial cell.

It has a bactericidal effect on gram-negative microorganisms during the period of rest and division (since it affects not only DNA gyrase, but also causes lysis of the cell wall), on gram-positive microorganisms - only during the period of division.

Low toxicity for the cells of the macroorganism is explained by the absence of DNA gyrase in them. While taking ciprofloxacin, there is no parallel development of resistance to antibacterial drugs that do not belong to the group of gyrase inhibitors, which makes it effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin: enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp. , Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.); some intracellular pathogens: Legionella pneumophila, Brucella spp., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii.

Gram-positive aerobic bacteria are also sensitive to ciprofloxacin: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Active against Bacillus anthracis.

Most staphylococci resistant to methicillin are also resistant to ciprofloxacin. The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required to suppress them).

The following are resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Not effective against Treponema pallidum.

Resistance develops extremely slowly, since, on the one hand, after the action of ciprofloxacin there are practically no persistent microorganisms left, and on the other hand, bacterial cells do not have enzymes that inactivate it.

The significance of the use of ciprofloxacin in clinical practice

One of the most striking and well-studied PCs is ciprofloxacin. All PCs have a bactericidal effect, which manifests itself at minimum inhibitory concentrations (MICs) or MICs exceeding no more than 2–4 times. Thus, it has been shown that for ciprofloxacin the MIC is 0.016–2 mg/l against P. Aeruginosa, however, there are pseudomonad strains that are resistant to ciprofloxacin - the MIC is from 8 to 32 mg/l, but ciprofloxacin still retains its advantages; Its activity against Legionella, Enterobacteriaceae, Y. Pestis should also be noted. Ciprofloxacin, like ofloxacin, demonstrates activity against gram-positive cocci [5]. PCs penetrate into the bacterial cell through the outer membrane: hydrophilic drugs penetrate through porin channels, through which, in addition to PCs, b-lactam ABs, tetracyclines, chloramphenicol, and aminoglycosides also penetrate. Hydrophobic PCs penetrate the polysaccharide layer. Thus, disruption of the permeability of, for example, porin channels will not affect permeability through the lipopolysaccharide layer. The process of PC removal from the cell is carried out by special carrier proteins [2]. PCs are DNA gyrase inhibitors. Blocking this enzyme leads to impaired division, bacteriostasis and rapid cell death. DNA gyrase belongs to the class of type II topoisomerases. Topoisomerases are found in both the cells of prokaryotes (bacteria) and eukaryotes (mammals), but this enzyme differs in structure and function in prokaryotes and eukaryotes; Thus, DNA gyrase is the main enzyme responsible for preparing DNA replication in the bacterial chromosome. These functions of DNA gyrase are characteristic only of bacteria; in mammals, a similar enzyme, topoisomerase II, does not catalyze DNA folding and is characterized by low sensitivity to PC, which explains the absence of toxic effects associated with impaired DNA biosynthesis. However, in the bacterial cell there is another target for PC – topoisomerase IV. Both enzymes (DNA gyrase and topoisomerase IV) are necessary for the synthesis of bacterial DNA, and it has been shown that in gram-negative bacteria the primary target is DNA gyrase, and in gram-positive bacteria topoisomerase is more sensitive to fluoroquinolones [5,11]. Thus, high intracellular concentrations and inhibition of target enzymes determine the high bactericidal activity of the drug. Antimicrobial activity. Ciprofloxacin is one of the most active against gram-negative aerobic bacteria (Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumonia, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Pro teus vulgaris, Providencia rettgeri, Pceudomonas aeruginosa, Salmonella, etc.), gram-positive asrobes (Bacillus anthracis, Enterococcus faecali (most strains are relatively sensitive), Lysteria monocitogenes, Staphylococcus aureus, Staphylococcus epiudermidis, Staphylococcus saprophyticus, Staphylococcus pneumoniae, Staphylococcus pyogens), anerobic gram-positive : Staphylococcus haemophilus, Staphylococcus hominis, anerobic gram-negative (Acinetobacter Iwoffi, Aeromonas caviae, Aeromonas hydrophilia, Brucella melitensis, Campylobacter coli, Edwadsiella tarda, Haemophilus ducreyi, Klebsiella oxytoca, Legionella pneumophila, Neisseria meningitides, etc.). Ciprofloxacin has a bactericidal effect not only on reproducing cells, but also on resting cells, which are characterized by the longest post-antibiotic effect. Ciprofloxacin demonstrates activity against organisms resistant to penicillins, cephalosporins and aminoglycosides, as well as against Haemophilus influenzae, penicillin-producing N. Gonorrhoa, Campilobacter sp., and pseudomonas. Gram-positive microorganisms, streptococci and pneumococci are weakly inhibited and demonstrate resistance; ciprofloxacin is not used in cases of methicillin-resistant staphylococcal infections [11]. It should be said that the nature of methicillin resistance has not been fully elucidated. The most likely and most proven cause is changes that occur in specific penicillin-binding proteins of the cell wall of staphylococci. Now there are new fluoroquinolones in the arsenal that are active against gram-positive cocci - moxifloxacin, gatifloxacin, clinafloxacin. These PCs demonstrate activity against ciprofloxacin-resistant Gram-positive bacteria that is much greater than that of vancomycin and ceftazidime. Pharmacokinetics. Ificipro®OD – long-acting ciprofloxacin – provides a long-lasting and uniform release of ciprofloxacin. A single dose of Ificipro®OD 0.5 g or 1.0 g provides a concentration of ciprofloxacin equivalent to a double dose of regular ciprofloxacin 250 mg or 500 mg, respectively. After oral administration, ciprofloxacin is rapidly absorbed from the gastrointestinal tract. Ificipro®OD 0.5 g tablets or Ificipro®OD 1.0 g tablets showed comparable rates and duration of absorption compared to immediate absorption of ciprofloxacin 250 mg and 500 mg tablets under the same study conditions. For ciprofloxacin - Ificipro®OD 0.5 g and Ificipro®OD 1.0 g after taking a single dose, peak plasma concentrations of the drug are reached within 6–7 hours and are 0.784 μg/ml and 1.393 μg/ml, respectively. The corresponding values ​​of the area under the pharmacokinetic curve (AUC0–t) are 10.503 and 17.651 μg/h/ml. Binding to plasma proteins is from 20 to 40%. Ciprofloxacin penetrates well into tissues and fluids of the body (lungs, skin, adipose tissue, muscles, cartilage and bone tissue, prostate). In its active form, ciprofloxacin is found in saliva, secretions of the mucous membrane of the nasal cavity and bronchi, semen, lymph, peritoneal fluid and prostate secretions. Ciprofloxacin is partially metabolized in the liver. About 50% of the dose taken orally is excreted in the urine unchanged and about 15% as the active metabolite of oxociprofloxacin. Renal clearance for ciprofloxacin is almost 2 times higher than glomerular filtration, because the drug is actively eliminated by transporter proteins. The remainder of the incoming dose is excreted extrarenally - with bile and through the intestines. The half-life is 3.5–4.5 hours, but it may be prolonged in cases of severe renal failure and in the elderly. Ciprofloxacin is an inhibitor of CYP1A2 and CYP3A4. The combined use of substrates of these isoenzymes and their inhibitors leads to inhibition of substrate metabolism and, as a consequence, to the development of side effects. For example, theophylline is a CYP1A2 substrate [2]. Ciprofloxacin had a less pronounced effect on the pharmacokinetics of theophylline. However, there are reports that a single dose of 500 mg of ciprofloxacin did not affect the pharmacokinetic parameters of theophylline in the stationary stage in healthy people; 5-day administration of ciprofloxacin in low doses (200 mg 3 times a day) only slightly increased serum concentrations of theophylline in healthy people, low doses of ciprofloxacin (11 doses of 250 mg 2 times a day) did not affect the steady-state concentrations of theophylline in the blood of patients with chronic obstructive pulmonary diseases [9]. Resistance. The development of resistance is associated with: 1) changes in the structure of target enzymes: DNA gyrase and topoisomerase IV; 2) disruption of transport systems - disruption of penetration into the cell (impaired entry through porin channels) and active removal from the cell, as well as increased expression of transport proteins. Such changes are encoded by the corresponding genes. Resistance is cross-linked only within the quinolone group and does not affect other AB drugs. Toxicity. When using PC under the influence of sunlight or UV radiation, phototoxic reactions are possible. Photodegradation of quinolone molecules under the influence of UV rays leads to the formation of free radicals and skin damage. It was also noted in experiments that PCs are inhibitors of g-aminobutyric acid receptors; inhibition increases when used together with NSAIDs. This must be taken into account in patients with a tendency to seizures. In experimental animals, when the urine is alkaline, high doses of PC can cause the formation of crystals. In clinical practice, crystalluria is extremely rare. Inhibition of hematopoiesis was also detected, which was brief and reversible. However, clinical observations indicate the safety of using PC in patients with disorders in the hematopoietic system. PCs are low-toxic drugs. Experimental studies revealed the inhibitory effect of PC on the growth of cartilage tissue in immature animals, because they can inhibit the biosynthesis of mitochondrial DNA in chondrocytes. In sexually mature animals, inhibition of cartilage tissue was not observed. Therefore, the use of quinolones is not recommended before 16–18 years of age. However, use is possible in exceptional cases with gram-negative flora resistant to other AB drugs. The use of fluoroquinolones is relevant in children with cystic fibrosis, with severe infections caused by Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens [6]. Clinical application. Today, the use of PC is an alternative to highly active broad-spectrum antibiotics. Ciprofloxacin has acquired the greatest importance in the treatment of severe generalized forms of bacterial infections caused predominantly by gram-negative bacteria and staphylococci with acquired resistance to antimicrobial drugs of other groups, including strains with multidrug resistance. There is no doubt about the proven clinical effectiveness in the treatment of community-acquired and hospital-acquired infections of almost any localization: - upper and lower respiratory tract, - urinary system, - skin and soft tissues, - bones and joints, - liver and biliary tract, - alimentary tract, - intra-abdominal infections, – gynecological infections, – eye infections, – central nervous system infections, – sexually transmitted infections. Lung infections. The use of ciprofloxacin and ofloxacin is relevant for nosocomial early ventilation pneumonia, mild pneumonia in the ICU, as well as for exacerbation of COPD [1]. The use of fluoroquinolones or macrolides for allergies to b-lactam ABs is justified. Ciprofloxacin is used in the elderly for community-acquired pneumonia as monotherapy or in combination with clindamycin or metronidazole or b-lactam ABs, as well as for “late” pneumonia in the elderly in combination with cefepime or piperacillin/tazobactam [4]. The results of one multicenter study in patients with pneumonia, bronchitis, and pulmonary infections in cystic fibrosis demonstrated clinical effectiveness in 60–70% of cases, and bacteriological effectiveness in 81% [5]. The effectiveness of ciprofloxacin in patients with exacerbation of COPD has been proven. The combination of high activity against H. influenzae and M. Catarrhalis, together with good penetration into sputum and bronchial mucosa, gives ciprofloxacin and ofloxacin advantages over b-lactam ABs. FQs demonstrate clinical effectiveness in 80–95% of cases during exacerbation of COPD. Ciprofloxacin is also more effective in terms of bacterial eradication (primarily Haemophilus influenzae) [7]. Urinary tract infections. Ciprofloxacin is often used for complicated and uncomplicated urinary tract infections. The most common lower urinary tract infection is acute cystitis, which statistically affects women most often. Most often this is one pathogen, and, as a rule, E. Coli (70–95%), the second place is occupied by S. Saprophyticus (5–20% of cases), Klebsiella, Proteus, streptococci, enterococci are even more rare. The justified use of ciprofloxacin for lower urinary tract infections is due to the fact that fluoroquinolones are the most active drugs against E. Coli, which has low resistance to this AB. Thus, it was shown that in Russia the resistance of E. Coli to ciprofloxacin is 2.6% versus 33% and 18% to ampicillin and co-trimoxazole, respectively. It should be noted that lower urinary tract infections are prone to self-healing; when choosing an AB, the occurrence of side effects should also be taken into account. The duration of use of ciprofloxacin for this pathology is 3–5 days, and in the presence of risk factors (diabetes mellitus, recurrent urinary tract infections, age over 65 years) up to 7 days 0.5–0.1 g/day. Single-dose positional treatment may be indicated for uncomplicated urinary tract infection without associated risk factors. In this situation, preference should be given to an AB with a long half-life, such as FQ. With the development of acute pyelonephritis, AB therapy is prescribed for a longer period of 10–14 days, and if ineffective – up to 4–6 weeks. In severe cases of pyelonephritis, as well as urosepsis without multiple organ failure, treatment begins with IV administration of AB with further transition to oral forms. For this purpose, ciprofloxacin 0.4–0.6 g/day is used. [5,8]. As a prophylaxis for frequent relapses of urinary tract infections (more than 2 exacerbations within a month or 3 times a year), low doses of ciprofloxacin 0.1 g/day are used, as well as nitrofurans and co-trimoxazole [3]. FQs are widely used in gynecology. It is known that inflammatory diseases of the pelvic organs are caused by various microorganisms that enter through the ascending route from the lower genital tract to the upper genital tract. The main pathogens are Chlamydia trachomatis, Mycoplasma spp., Ureaplasma urealyticum, Neisseria gonorrhoeae, Streptococcus spp., Escherichia coli, Haemophilus influenzae, etc., as well as anaerobes such as Prevotella spp. and Peptostreptococcus. Accurate etiotropic diagnosis is very difficult and takes a lot of time, so in many cases treatment is carried out empirically, and therefore it should cover the majority of likely pathogenic microorganisms. Osteomyelitis remains a disease that is difficult to treat today. Ciprofloxacin shows good efficacy and tolerability (duration of administration from several weeks to a year or more) for this pathology. There is evidence of clinical effectiveness ranging from 75 to 92% [5]. Infections of the skin and soft tissues (cellulitis, subcutaneous abscesses, wound infections (traumatic or postoperative) and infections of ulcers of the lower extremities (usually in patients with diabetes). Along with the usual microorganisms found in cellulitis and subcutaneous abscesses (staphylococci, streptococci), currently time, various gram-negative microbes are often isolated - Pseudomonas, Serratia, Enterobacter, Citrobacter, Acinetobacter, etc. (often in associations and multi-resistant to antibiotics), the treatment of which is very difficult.The use of ciprofloxacin, which penetrates well into tissues, allows you to successfully treat these severe infections , moreover, the effectiveness of ciprofloxacin is not inferior to third-generation cephalosporins (ceftazidime and cefatoxime) [10]. Good results have been obtained regarding the clinical effectiveness of ciprofloxacin for abdominal infections. There are reports that for peritonitis, abscesses, cholecystitis, pancreatitis and other diseases of the abdominal cavity, caused by E. Coli, clinical and bacteriological effect was obtained in more than 90% of cases [5]. Sepsis. One of the most serious and life-threatening infections. Several drugs with a broad spectrum and low level of sensitivity should be noted. These include carbapenems (imipenem, meropenem), IV generation cephalosporins (cefepime), fluoroquinolones (ciprofloxacin, ofloxacin) [10]. Ciprofloxacin is recommended for inclusion as the 3rd, 4th or 5th drug in the treatment of tuberculosis (in combination with other antituberculosis drugs). This is especially important in cases of drug-resistant forms of tuberculosis. An important quality is that the drug is well tolerated; it can be combined with anti-tuberculosis drugs and used for long courses [5]. Ciprofloxacin is active against gonococci and is ineffective against genital non-gonococcal infections. It also demonstrates good effectiveness against enteropathogenic infections. Thus, ciprofloxacin has proven itself well in the treatment of shigilesis and salmonellosis. Ciprofloxacin is used as a reserve drug in the treatment of infections of the central nervous system when standard antibacterial drugs have exhausted themselves. For AIDS patients with M. avium infection, the inclusion of ciprofloxacin in complex antibacterial therapy is indicated, although the effectiveness of such treatment is not yet high enough. Interactions. Activity increases when combined with b-lactam antibiotics, aminoglycosides, vancomycin, clindamycin, metronidazole. Studies conducted with antacids containing aluminum and magnesium ions have shown their pronounced effect on the absorption of fluoroquinolones from the gastrointestinal tract. At the same time, the severity of changes in absorption was ambiguous for different drugs of the PC group. The use of antacids containing metals, especially aluminum and magnesium, with fluoroquinolons leads to the formation of chelat complexes that do not have antibacterial activity, as a result of which the concentration of chinolone in the body can decrease to a level that may affect the results of treatment, significantly reducing the effectiveness of therapy. In connection with the formation of helates in patients who received ciprofloxacin for the treatment of bacteriuria and who had high concentrations of magnesium in the urine (or as a result of taking antacids containing magnesium, or as a result of taking diuretics that increase magnesium excretion), you can not get the expected antibacterial action Hinolon [10]. Due to the fact that the solubility of ciprofloxacin is reduced with alkaline values ​​of the pH, an increased formation of crystals in the urine of patients receiving Bicarbonate salts and other alkylation agents simultaneously with chinolone can be observed. The formation of crystals in acidic urine was not noted when taking NH4CL. The use of antagonists H2 - receptors increases the stomach pH from 2.0 to 6.0. The solubility of fluoroquinolons at these values ​​of the pH is significantly reduced, omeprazole does not affect the FC of Ciprofloxacin. There are reports of the appearance of fluoroquinolons and non -steroidal anti -inflammatory drugs in a number of patients with simultaneous seizures. Probenecide, azlocillin increase the concentration in the blood, as they are inhibitors of transporters in renal tubules. Enhances the action of warfarin and other oral anticoagulants (lengthens the time of bleeding). Increases the nephrotoxicity of cyclosporine. Side effects. Ciprofloxacin is well tolerated by patients, side effects develop in 4–8% of cases and are mild and moderate. Most of the side effects are observed from the gastrointestinal tract (nausea, vomiting, diarrhea, cholestatic jaundice, especially in patients with a history of liver diseases) - no more than 5%, from the part of the central nervous system there is globe, headache, insomnia - about 1.5%, allergic Reactions are found in 1.4% of cases [5]. Contraindications: pseudomembranous colitis; Increased sensitivity to ciprofloxacin or other derivatives of fluoroquinolones. As for the use of ciprofloxacin in children, pregnant and lactating women, these restrictions on the use of fluoroquinolons will be revised, because Over the period of more than 15 years of use, not a single serious complication from the bone -cold system has been revealed in this category [5]. The conclusion of the widespread use of FC is associated with their: 1) antimicrobial activity (the degree of penetration into the microbial cell, good bactericidal activity, preservation of the antimicrobial effect with minimal overwhelming concentration, the plain effect, the ability to accumulate in the cells of the phagocytic system, which is important for the treatment of pathogens with intracellular localization, slow development of stability); 2) pharmacokinetic characteristics (high bioavailability, good penetration into organs and tissues, the creation of high concentrations in the foci of infections, low binding to plasma proteins, slow excretion from the body, which allows you to use a two -time and even single intake per day, elimination of both renal and renal and renal intake Outside ways, the lack of cumulation), in particular, the drug Irf and the OOD is a prolonged cyprofloxacin, which provides the maximum effect of the drug with a single use and good compliance of patients; 3) high clinical efficiency, good tolerance and low frequency of development of side effects. All this makes fluoroquinolones indispensable in the arsenal of a general practitioner. However, one should not forget about the resistance of bacteria to FC. There are reports of increasing resistance to FC S. aureus and P. Aeruginosa, so the purpose of the FC should be justified. Literature 1. Domnikova N.P., Sidorova L.D. Antibacterial therapy of nosocomial pneumonia. RMG, T.3, No. 1–2, 2001, pp. 17–21. 2. Kukes V.G. Medication metabolism: clinical and pharmacological aspects. M., 2004, pp. 36–37, 130–136. 3. Lopatkin N.A., Derevyanko I.I., Strachunsky L.S. et al. Antibacterial therapy of uncomplicated acute cystia and pyelonephritis in adults. Clinical microbiology and antimicrobial chemotherapy. T.2, No. 1, 2000, pp. 69–76. 4. Nonikov V.E. Pneumonia in the elderly and senile age: diagnosis and treatment. Consilium –Mtdicum. T. 5, No. 3, 2003, pp. 691–695. 5. Paseskaya E.N., Yakovlev V.P. Antimicrobial drugs of the Forchinolon group in clinical practice. Logata. M., 1998. 6. Tatochenko V.K., Sereda E.V., Fedorov A.M. Antibacterial therapy of pneumonia in children. Edited by Strachunsky L.S. Clinical microbiology and antimicrobial chemotherapy. T.2, No. 1, 2000, pp. 77–87. 7. Chuchalin A.G. Chronic obstructive lung diseases. Nevsky dialect. S - Petersburg, 1998, pp. 321–337. 8. Yakovlev S.V. Programs of microbiological diagnosis and antibacterial therapy of sepsis. Infections and antimicrobial therapy. Consilium –Medicum. T. 3, No. 3, 2001, pp. 90–91. 9. Yakovlev V.P., Yakovlev S.V. Pharmacokinetic interaction between fluoroquinolons and methylxantins. Antibiotics and chemotherapy, N3, 1999, pp. 35–41. 10. Yakovlev V.P. Pharmacokinetic interaction between fluoroquinolones and other drugs antibiotics and chemotherapy. No. 7, 1998, pp. 36–44. 11. Rang HP, Dale MM, Ritter JM, Moore PK PHARMACOLOGY. Churchill LivingStone, UK, 2003, p. 648.

Indications for use

Infectious and inflammatory diseases caused by sensitive microorganisms:

lower respiratory tract infections (acute bronchitis and chronic bronchitis in the acute stage, pneumonia, bronchiectasis, infectious complications of cystic fibrosis); ENT infections (acute sinusitis); kidney and urinary tract infections (cystitis, pyelonephritis); complicated intra-abdominal infections (in combination with metronidazole); chronic bacterial prostatitis; uncomplicated gonorrhea; typhoid fever, campylobacteriosis, shigellosis, traveler's diarrhea; infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon); infections of bones and joints (osteomyelitis, septic arthritis); infections due to immunodeficiency (occurring during treatment with immunosuppressive drugs or in patients with neutropenia); prevention and treatment of pulmonary anthrax;

Children:

prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis) from 6 years of age.

Directions for use and doses

Inside. The tablets should be swallowed whole with a small amount of liquid after meals. When taking the tablet on an empty stomach, the active substance is absorbed faster.

• For mild and moderate lower respiratory tract infections - 0.5 g 2 times a day, for severe infections - 0.75 g 2 times. The course of treatment is 7-14 days.
• For acute sinusitis - 0.5 g 2 times a day. The course of treatment is 10 days.
• For mild to moderate skin and soft tissue infections - 0.5 g 2 times a day, for severe infections - 0.75 g 2 times. The course of treatment is 7-14 days.
• For infections of bones and joints - mild and moderate - 0.5 g 2 times a day, for severe infections - 0.75 g 2 times. The course of treatment is up to 4-6 weeks.
• For uncomplicated urinary tract infections - 0.25-0.5 g 2 times a day; course of treatment - 7-14 days, for complicated urinary tract infections 0.5 g every 12 hours for 7-14 days.
• For chronic prostatitis - 0.5 g 2 times, course of treatment - 28 days.
• For uncomplicated gonorrhea - 0.25 g once.
• Acute intestinal infections with severe course (salmonellosis, shigellosis, campylobacteriosis, etc.) - 0.5 g 2 times, course of treatment - 5-7 days.
• For typhoid fever - 0.5 g 2 times; course of treatment - 10 days.
• For complicated intra-abdominal infections - 0.5 g every 12 hours for 7-14 days.
• For the prevention and treatment of pulmonary anthrax - 0.5 g 2 times a day for 60 days.
• In patients with immunodeficiency, treatment is prescribed depending on the severity of the infection and the type of pathogen. Therapy is carried out throughout the entire period of neutropenia.
• Chronic renal failure: when creatinine clearance (CC) is more than 50 ml/min, no dose adjustment is required; with CC 30-50 ml/min - 0.25-0.5 every 12 hours; with CC 5-29 ml/min - 0.25-0.5 g every 18 hours. If the patient is undergoing hemodialysis or peritoneal dialysis - 0.25-0.5 g/day, the drug should be taken after the hemodialysis session.
• In pediatrics: for
  pulmonary anthrax (prevention and treatment) - 15 mg/kg 2 times a day. The maximum single dose is 0.5 g, the daily dose is 1 g. The total duration of taking ciprofloxacin is 60 days.

Side effects

anorexia, nausea, vomiting, abdominal pain, flatulence, diarrhea, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis; dizziness, headache, increased fatigue, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (anomaly in the perception of pain), sweating, increased intracranial pressure, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions (rarely progressing to conditions in which the patient may harm himself).

Rarely:

migraine, fainting, thrombosis of cerebral arteries; disturbances of taste and smell, visual disturbances (diplopia, changes in color vision), tinnitus, hearing loss; tachycardia, heart rhythm disturbances, prolongation of the QT interval, decreased blood pressure; leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia; hypoprothrombinemia, increased activity of liver transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia; hematuria, crystalluria (primarily with alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, decreased nitrogen excretory function of the kidneys, interstitial nephritis; pruritus, urticaria, blistering accompanied by bleeding and the appearance of small nodules that form scabs, drug fever, pinpoint hemorrhages on the skin (petechiae), swelling of the face or larynx, shortness of breath, eosinophilia, vasculitis, erythema nodosum, exudative erythema multiforme, Stevens syndrome -Johnson (malignant exudative erythema), toxic epidermal necrolysis (Lyell's syndrome); arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia; general weakness, increased photosensitivity, superinfections (candidiasis, pseudomembranous colitis), “flushes” of blood to the face.

Side effects of the drug Ciprofloxacin

Generally well tolerated, but the following side effects may occur: dizziness, headache, fatigue, agitation, tremor; in isolated cases - peripheral sensitivity disorders, sweating, hot flashes, gait disturbance, increased intracranial pressure, a feeling of fear, depression, visual disturbances; nausea, vomiting, diarrhea, indigestion, abdominal pain, flatulence, hepatitis, necrosis of liver cells; tachycardia, rarely - hypertension (arterial hypertension); skin itching, rash; extremely rarely - Quincke's edema, bronchospasm, arthralgia; anaphylactic shock, petechiae, vasculitis, Stevens-Johnson syndrome, Lyell's syndrome; eosinophilia, leukopenia, anemia, thrombocytopenia; leukocytosis, thrombocytosis, hemolytic anemia; increased levels of creatinine, liver transaminases, alkaline phosphatase, LDH, and bilirubin in the blood serum.

Contraindications

hypersensitivity to ciprofloxacin, other fluoroquinolones, auxiliary components of the drug; simultaneous use with tizanidine (risk of a pronounced decrease in blood pressure, drowsiness); childhood and adolescence up to 18 years of age (until the process of skeletal formation is completed), prevention and treatment of pulmonary anthrax - children up to 6 years of age; pregnancy and lactation; tendon damage due to previous treatment with fluoroquinolones; tendon lesions, including tenosynovitis, tendon rupture, muscle lesions (rhabdomyolysis); pseudomembranous colitis.

Drug interactions Ciprofloxacin

The simultaneous use of ciprofloxacin and theophylline may lead to an increase in the plasma concentration of theophylline and an increase in its half-life. Probenecid slows down the elimination of ciprofloxacin. Antacids containing magnesium hydroxide and/or aluminum hydroxide can slow down the absorption of ciprofloxacin, which leads to a decrease in its concentration in the blood serum and urine, so the interval between doses of these drugs should be at least 4 hours. Ciprofloxacin potentiates the effect of coumarin anticoagulants.

List of pharmacies where you can buy Ciprofloxacin:

• Moscow
• Saint Petersburg

Drug interactions

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and lengthens the half-life of theophylline (and other xanthines, such as caffeine), oral hypoglycemic drugs, and indirect anticoagulants.

When combined with other antimicrobial drugs (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole), synergism is usually observed; can be successfully used in combination with azlocillin and ceftazidime for infections caused by Pseudomonas spp.; with mezlocillin, azlocillin and other beta-lactam antibiotics - for streptococcal infections; with isoxazolylpenicillins and vancomycin - for staphylococcal infections; with metronidazole and clindamycin - for anaerobic infections.

It enhances the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine; in such patients it is necessary to monitor this indicator 2 times a week.

When taken simultaneously, it enhances the effect of indirect anticoagulants and helps reduce the prothrombin index.

Oral administration together with iron-containing drugs, sucralfate and antacid drugs containing magnesium, calcium and aluminum salts leads to decreased absorption of ciprofloxacin, so it should be prescribed 1-2 hours before or 4 hours after taking the above drugs.

Non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of developing seizures.

Fluoroquinolones form chelate compounds with magnesium and aluminum ions contained in the dosage form of didanosine, which sharply reduces the absorption of fluoroquinolone, so ciprofloxacin is taken 2 hours before taking didanosine or 2 hours after taking this drug.

Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its maximum concentration in the blood plasma.

Co-administration of uricosuric drugs leads to a slower elimination (up to 50%) and an increase in plasma concentrations of ciprofloxacin.

Increases the maximum concentration by 7 times (from 4 to 21 times) and the area under the concentration-time curve by 10 times (from 6 to 24 times) of tizanidine, which increases the risk of a pronounced decrease in blood pressure and drowsiness.

Pharmacological properties of the drug Ciprofloxacin

ciprofloxacin is a broad-spectrum antimicrobial agent of the fluoroquinolone group. It has a bactericidal effect, the mechanism of which is due to the inhibition of bacterial DNA gyrase with disruption of DNA synthesis, growth and division of microorganisms. It has an antimicrobial effect with the greatest activity against aerobic gram-negative and gram-positive bacteria: Pseudomonas aeruginosa, Haemophilus influenzae, Escherichia coli, Shigella spp., Salmonella spp., Neisseria meningitidis, N. gonorrhoeae. Active against many strains of Staphylococcus spp. (producing and not producing penicillinase), some strains of Enterococcus spp ., as well as Campylobacter spp., Legionella spp., Mycoplasma spp., Chlamidia spp., Mycobacterium spp. Ciprofloxacin is active against bacteria that produce beta-lactamases. Streptococcus faecium, Ureaplasma urealyticum, Nocardia asteroides, Treponema pallidum are resistant to ciprofloxacin Bacterial resistance to ciprofloxacin develops slowly. When taken orally, it is quickly and completely absorbed from the digestive tract. The maximum plasma concentration is reached 1–2 hours after administration, bioavailability is 70%, and the half-life is 4 hours. Approximately 20–40% of ciprofloxacin is bound to plasma proteins. Ciprofloxacin is well distributed in tissues and biological fluids of the body, and its concentration can significantly exceed the concentration in blood plasma. Penetrates into the cerebrospinal fluid through the placenta, excreted in breast milk, high concentrations are determined in bile. Up to 40% is excreted from the body with urine (unchanged) within 24 hours, partially with bile.

special instructions

Ciprofloxacin is not the drug of choice for suspected or established pneumonia caused by Streptococcus pneumoniae.

To avoid the development of crystalluria, it is unacceptable to exceed the recommended daily dose; sufficient fluid intake and maintaining an acidic urine reaction are also necessary.

Patients with epilepsy, a history of seizures, vascular diseases and organic brain damage due to the threat of adverse reactions from the central nervous system should be prescribed ciprofloxacin only for “vital” indications.

If severe and prolonged diarrhea occurs during or after treatment with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

If pain occurs in the tendons or when the first signs of tenosynovitis appear, treatment should be stopped due to the fact that isolated cases of inflammation and even tendon rupture have been described during treatment with fluoroquinolones.

During treatment with ciprofloxacin, UV radiation (including contact with direct sunlight) should be avoided.

Features of the effect of the drug on the ability to drive a vehicle or other potentially dangerous mechanisms.

During treatment, you should refrain from engaging in potentially hazardous activities that require increased attention and speed of mental and motor reactions.

Release form and packaging

10 tablets with a dosage of 250 mg or 5 tablets with a dosage of 500 mg are placed in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil (PVC/Al) or soft aluminum foil and hard aluminum foil (Al/Al).

1 or 2 blister packs with a dosage of 250 mg or 2 blister packs with a dosage of 500 mg, together with instructions for medical use in the state and Russian languages, are placed in a cardboard pack.