CIPROFLOXACIN TEVA tablet. p/o captivity. 500 mg No. 10
Side effects
From the digestive system: nausea, diarrhea, vomiting, abdominal pain, flatulence, anorexia, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis. From the central nervous system and peripheral nervous system: dizziness, headache, increased fatigue, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (anomaly in the perception of pain), sweating, increased intracranial pressure, anxiety, confusion, depression, hallucinations, manifestations psychotic reactions (sometimes progressing to states in which the patient can harm himself), migraine, fainting, cerebral artery thrombosis. From the senses: disturbances of taste and smell, visual impairment (diplopia, changes in color vision), tinnitus, hearing loss. From the cardiovascular system: tachycardia, heart rhythm disturbances, decreased blood pressure, flushing of the face. From the hematopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia. Laboratory indicators: hypoprothrombinemia, increased activity of liver transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia. From the urinary system: hematuria, crystalluria (primarily with alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, hematuria, decreased nitrogen excretory function of the kidneys, interstitial nephritis. From the musculoskeletal system: arthralgia, arthritis, tenosynovitis, tendon ruptures, myalgia. Allergic reactions: skin itching, urticaria, blistering accompanied by bleeding, papules that form scabs, drug fever, pinpoint hemorrhages (petechiae), swelling of the face or larynx, shortness of breath, eosinophilia, increased photosensitivity, vasculitis, erythema nodosum, exudative erythema multiforme, syndrome Stevens-Johnson, toxic epidermal necrolysis (Lyell's syndrome). Other: arthralgia, arthritis, tenosynovitis, tendon ruptures, general weakness, myalgia, superinfections (candidiasis, pseudomembranous colitis), pain and burning at the injection site, phlebitis.
Ciprofloxacin-Teva tablet p/p/o 500 mg 10 pcs
Pharmacological group:
antimicrobial agent - fluoroquinolone
Pharmacodynamics:
Ciprofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones.
Mechanism of action Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal effect of ciprofloxacin is carried out through the inhibition of bacterial type II topoisomerases (topoisomerase II (DNA gyrase) and topoisomerase IV), which are necessary for the replication, transcription, repair and recombination of bacterial DNA.
Mechanisms of resistance In vitro resistance to ciprofloxacin is often caused by point mutations in bacterial topoisomerases and DNA gyrase and develops slowly through multistep mutations.
Single mutations may result in decreased susceptibility rather than the development of clinical resistance, but multiple mutations generally lead to the development of clinical resistance to ciprofloxacin and cross-resistance to quinolone drugs. Resistance to ciprofloxacin, as to many other antibiotics, can develop as a result of decreased permeability of the bacterial cell wall (as often occurs in the case of Pseudomonas aeruginosa) and/or activation of elimination from the microbial cell (efflux).
The development of resistance caused by the Qnr coding gene localized on plasmids has been reported. Resistance mechanisms that lead to inactivation of penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not likely 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 susceptibility testing Reproducible criteria for susceptibility testing for ciprofloxacin, approved by the European Committee on Antibiotic Susceptibility Testing (EUCAST), are presented in the table below: European Committee on Antibiotic Susceptibility Testing.
Clinical MIC breakpoints (mg/l) for ciprofloxacin Microorganism Susceptible [mg/l] Resistant [mg/l] Enterobacteriaceae 1 Pseudomonas spp. 1 Acinetobacter spp. 1 Staphylococcus1 spp. 1 Streptococcus pneumoniae2 2 Neisseria gonorrhoeae 0.06 Neisseria meningitides 0.06 Haemophilys influenzae u 0.5 Moraxella catarrhalis3 Boundary values, 1 not related to microorganism species4 1. Staphylococcus spp. — breakpoints for ciprofloxacin and ofloxacin are associated with high-dose therapy.
2. Streptococcus pneumoniae - wild type S. pneumoniae is not considered susceptible to ciprofloxacin and ofloxacin and is therefore classified as intermediately susceptible.
3. Strains with MIC values exceeding the sensitive/moderately sensitive threshold ratio are very rare and have not been reported to date. Identification and antimicrobial susceptibility tests should be repeated when such colonies are detected, and the results should be confirmed by colony testing at a reference laboratory. Until evidence of clinical response is available for strains with confirmed MIC values above the currently used resistance threshold, they should be considered resistant.
Haemophilus spp. /Moraxella spp. — it is possible to identify strains of Haemophilus influenzae with low sensitivity to fluoroquinolones (MIC for ciprofloxacin - 0.125-0.5 mg/l). There is no evidence of the clinical significance of low resistance in respiratory tract infections caused by H. influenzae.
4. Non-species-specific breakpoints were determined primarily on the basis of pharmacokinetics/pharmacodynamics data and are independent of species-specific MIC distributions. They are only applicable to species for which a species-specific susceptibility threshold has not been determined, and not to those species for which susceptibility testing is not recommended. For certain strains, the distribution of acquired resistance may vary across geographic regions and over time. Therefore, it is desirable to have local information on resistance, especially when treating serious infections.
Clinical and Laboratory Standards Institute data for MIC breakpoints (mg/L) and diffusion testing (zone diameter [mm]) using discs containing 5 mcg ciprofloxacin are presented in the table below.
Clinical and Laboratory Standards Institute. Breakpoints for MIC (mg/l) and for diffusion testing (mm) using disks Microorganism Sensitive Intermediate Resistant Enterobacteriaceae 4a > 21b 16-20b 4a belonging to the family > 21b 16-20b Epterobacteriaceae Staphylococcus spp 4a > 21b 16-20b 4a > 21b 16-20b 21g — — Neisseria gonorrhoeae 1d > 41d 28–40d 0.12f > 35g 33-34g
V. This reproducible standard is only applicable to susceptibility disk diffusion tests with Haemophilus influenzae and Haemophilus parainfluenzae using broth test medium for Haemophilus spp. (HTM), which is incubated with air at a temperature of 35°C ± 2°C for 20-24 hours.
d. This reproducible standard is only applicable to disc diffusion tests using NTM, which is incubated in 5% CO2 at 35°C ± 2°C for 16-18 hours.
e. This reproducible standard is only applicable to susceptibility tests (zone disc diffusion tests and MIC agar solution) using gonococcal agar and 1% specified growth supplement at 36°C ± 1°C (not to exceed 37°C) in 5% CO2 for 20-24 hours.
e. This reproducible standard is only applicable to broth dilution tests using cationically adjusted Mueller-Hinton broth (CAMHB) supplemented with 5% sheep blood, incubated in 5% CO2 at 35 ± 2 °C for 20-24 h. .
and. This reproducible standard is only applicable to broth dilution tests using cationically adjusted Mueller-Hinton broth (CAMHB) supplemented with a specified 2% growth supplement and incubated with air at 35 ± 2°C for 48 hours.
In vitro susceptibility to ciprofloxacin For certain strains, the distribution of acquired resistance may vary depending on the geographical region and over time. Therefore, it is desirable to have local information on resistance when testing strain susceptibility, especially when treating severe infections. If the local prevalence of resistance is such that the benefit of using the drug, at least against several types of infections, is questionable, it is necessary to consult a specialist.
In vitro activity of ciprofloxacin has been demonstrated against the following sensitive strains of microorganisms:
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., Haemophilius influenzae, Vibrio spp., Legionella spp., Yersinia pestis.
Anaerobic microorganisms: Mobiluncus spp.
Other microorganisms: Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.
Varying degrees of sensitivity to ciprofloxacin have been demonstrated for the following microorganisms: 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 Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enterococcus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (with the exception of Mobiluncus spp., Peptostreptococus spp., Propionibacterium) have natural resistance to ciprofloxacin acnes ).
Pharmacokinetics:
Suction.
After oral administration, ciprofloxacin is rapidly 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 plasma concentration (Cmax) and the area under the concentration-time curve (AUC) increase in proportion to the dose.
Distribution.
The binding of ciprofloxacin to plasma proteins is 20-30%; the active substance is present in blood plasma mainly in non-ionized form. Ciprofloxacin is 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 significantly exceeds the concentration in serum.
Metabolism.
Biotransformed in the liver. Four metabolites of ciprofloxacin can be detected in the blood in small concentrations: diethylciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), formylciprofloxacin (M4), three of which (M1-M3) exhibit antibacterial activity in vitro, comparable to the antibacterial activity of nalidix acids. The in vitro antibacterial activity of the M4 metabolite, present in smaller quantities, is more consistent with the activity of norfloxacin.
Excretion.
Ciprofloxacin is excreted from the body primarily by the kidneys by glomerular filtration and tubular secretion; a small amount - through the gastrointestinal tract. Renal clearance is 0.18-6.3 l/h/kg, total clearance is 0.48-0.60 l/h/kg. Approximately 1% of the administered dose is excreted in bile. Ciprofloxacin is present in bile in high concentrations. In patients with unchanged renal function, the half-life is usually 3-5 hours. If renal function is impaired, the half-life increases.
