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Active ingredients
Tinidazole + Ciprofloxacin
Release form
Pills
Composition
1 tablet contains: Ciprofloxacin hydrochloride monohydrate 582,285 mg, which corresponds to the content of ciprofloxacin 500 mgTinidazol 600 mgVspomogatelnye ingredients: corn starch - 35 mg Sodium croscarmellose - 27,476 mg microcrystalline cellulose - 20.33 mg sodium carboxymethyl starch (type A) - 5 mg, silicon colloidal dioxide - 3.952 mg, talc - 8.952 mg, magnesium stearate - 7 mg. The composition of the shell: opadry white - 40 mg (hypromellose - 55.46%, talc - 19.84%, titanium dioxide - 11.93%, macrogol 6000 - 11.09%, polysorbate 80 - 0.84%, sorbic acid - 0.84%).
Pharmacological effect
A combination drug whose effect is due to its constituent components. Ciprofloxacin is a broad-spectrum antimicrobial agent, a fluoroquinolone derivative, suppresses bacterial DNA gyrase (topoisomerases II and IV, which are responsible for the supercoiling of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), violates the synthesis of DNA, growth and division of bacteria; causes pronounced morphological changes (including the cell wall and membranes) and the rapid death of the bacterial cell. It acts bactericidal on gram-negative organisms during rest and division (because it affects not only DNA gyrase, but also causes lysis of the cell wall), Gram-positive microorganisms - only in the period of division. Low toxicity to cells of the microorganism is explained by the absence of DNA gyrase in them. While receiving ciprofloxacin, parallel development of resistance to other antibiotics that do not belong to the group of gyrase inhibitors does not occur, which makes it highly effective against bacteria that are resistant to aminoglycosides, penicillins, cephalosporins, tetracyclines, antibiotics. : 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, peladeli, sherbella algari, Edwardiella tarda, Providencia spp., Morganella sard. 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: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae). Most methicillin resistant staphylococci are resistant to ciprofloxacin.Resistance develops extremely slowly, since, on the one hand, after the action of ciprofloxacin, there are practically no persistent microorganisms, and on the other hand, bacterial cells do not have inactivating enzymes. , Nocardia asteroides. It is not effective against Treponema pallidum. Tinidazole is an antiprotozoal and antimicrobial agent derived from imidazole. Active against Trichomonas vaginalis, Entamoeba histolitica, Lamblia, and also causative agents of anaerobic infections - Clostridium spp., Bacteroides fragilis, Bacteroides melaninogenicus, Eubacter spp., Fusobacterium spp., Peptococcus spp. and Peptostreptococcus spp. Being a highly lipophilic compound, tinidazole penetrates into Trichomonas and anaerobic microorganisms, where it is reduced by nitroreductase, inhibits synthesis and damages the structure of DNA.
Pharmacokinetics
Suction As ciprofloxacin, and tinidazole are well absorbed from the gastrointestinal tract after oral administration. Food intake slows down the absorption, but does not change the Cmax value and bioavailability. Distribution Ciprofloxacin Bioavailability - 50-85%, Vd - 2-3.5 l / kg, plasma protein binding - 20-40%, Tmax after oral administration - 60-90 min, Cmax after ingestion in a dose of 500 mg - 0.2 mcg / ml. Tinidazol Bioavailability - 100%, binding to plasma proteins - 12%, Tmax after ingestion - 2 hours, Cmax after ingestion in a dose of 500 mg - 47.7 mcg / ml. Metabolism and elimination of Tinidazole penetrates into the cerebrospinal fluid at a concentration equal to that in plasma and undergoes reabsorption in the renal canal Alzah. T1 / 2 - 12-14 h. Tinidazole is metabolized in the liver with the participation of the cytochrome P450 enzyme system (CYP3A4). About 50% is excreted in the bile, 25% in the kidneys, 12% in the form of metabolites. It is reabsorbed in the renal tubules. Ciprofloxacin penetrates well into fluids and tissues of the body (excluding tissue rich in fats, for example, nervous tissue). The concentration in the tissues is 2-12 times higher than in plasma. Therapeutic concentrations are reached in saliva, tonsils, liver, gallbladder, bile, intestines, abdominal organs and small pelvis, uterus, seminal fluid, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary organs, lung tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. In the spinal fluid penetrates in a small amount, where its concentration, in the absence of inflammation of the meninges, is 6-10% of the serum, and when inflamed - 14-37%. Ciprofloxacin also penetrates well into the eye fluid, bronchial secretion, pleura, peritoneum, lymph, through the placenta.The concentration of ciprofloxacin in neutrophils is 2-7 times higher than in plasma. Activity decreases slightly with pH values less than 6. Metabolized in the liver (15-30%) with the formation of low-level metabolites (diethylcyrofloxacin, sulfocyrofloxacin, oxo-cyprofloxacin, formylcyrofloxacin) .T1 / 2 - about 4 hours. canalicular secretion unchanged (40-50%) and in the form of metabolites (15%), the rest - through the gastrointestinal tract. A small amount is excreted in breast milk. Renal clearance - 3-5 ml / min / kg; total clearance - 8-10 ml / min / kg. Pharmacokinetics in special clinical situations. The pharmacokinetic parameters of tinidazole in patients with chronic renal failure (CC above 22 ml / min) do not differ from those in healthy people. Ciprofloxacin with chronic renal failure T1 / 2 increases up to 12 hours. With CRF (CC above 20 ml / min), the percentage of the drug excreted through the kidneys decreases, but does not cumulate in the body due to a compensatory increase in the metabolism of the drug and its elimination through the gastrointestinal tract.
Indications
Mixed bacterial infections caused by susceptible Gram-positive and Gram-negative microorganisms, in association with anaerobic microorganisms and / or protozoa: - respiratory tract infections (acute bronchitis, chronic bronchitis in the acute stage, pneumonia, bronchiectasis); - LOR-organ infections (otitis media, sinusitis, frontal sinusitis, mastoiditis, tonsillitis, pharyngitis); - oral infections (acute ulcerative gingivitis, periodontitis, periostitis); - infections of the kidneys and urinary tract (cystitis, pyelonephritis); - infections of the pelvic organs and genital organs (prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, pelvioperitonitis); - intra-abdominal infections (infections of the gastrointestinal tract, biliary tract, intraperitoneal abscesses); - infections of the skin and soft tissues (infected ulcers, wounds , burns, abscesses, phlegmon, ulcerative skin lesions in diabetic foot syndrome, bedsores); - infections of bones and joints (osteomyelitis, septic arthritis); - postoperative infections.
Contraindications
- blood diseases (in history); - inhibition of bone marrow hematopoiesis; - organic diseases of the central nervous system; - pregnancy; - lactation period (breastfeeding); - concomitant use with tizanidine (risk of marked decrease in blood pressure,drowsiness); - acute porphyria; - children and adolescents under 18 years of age; - hypersensitivity to the drug components; - hypersensitivity to fluoroquinolone or imidazole derivatives.
Precautionary measures
The drug should be prescribed with caution in case of diseases of the central nervous system: epilepsy, lowering the threshold of convulsive readiness (or convulsive seizures in history), while reducing blood flow in the vessels of the brain, organic brain lesions or stroke; mental illness (depression, psychosis); with renal failure (also accompanied by liver failure), elderly patients.
Use during pregnancy and lactation
The drug is contraindicated during pregnancy and lactation (breastfeeding). Tinidazole and ciprofloxacin are excreted in breast milk, therefore, for the period of drug treatment, breastfeeding should be stopped, because tinidazole may have a mutagenic and carcinogenic effect.
Dosage and administration
The drug is prescribed orally, 1 hour before meals or 2 hours after meals. The recommended dose is 1 tab. 2 times / day for 5-10 days. Tablets should be taken with a large amount of water. Do not crush, chew or destroy the tablet.
Side effects
On the part of the digestive system: loss of appetite, dryness of the oral mucosa, metallic taste in the mouth, nausea, vomiting, diarrhea, abdominal pain, flatulence, cholestatic jaundice (especially in patients with past liver disease), hepatitis, hepatonecrosis. On the side of the CNS and peripheral nervous system: headache, dizziness, fatigue, impaired motor coordination (including locomotor ataxia), dysarthria, peripheral neuropathy; rarely - convulsions, weakness, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (anomaly of perception of pain), increased intracranial pressure, confusion, depression, hallucinations, and other manifestations of psychotic reactions, migraine, fainting, cerebral arteries thrombosis , increased sweating. On the part of the senses: taste and smell disturbances, visual disturbances (diplopia, change in color perception), tinnitus, hearing loss. On the part of the cardiovascular system: t hikardiya, arrhythmia, reduced AD.So side of hematopoiesis: leukopenia, granulocytopenia, anemia (includinghemolytic), thrombocytopenia, leukocytosis, thrombocytosis. From the urinary system: hematuria, crystalluria (when alkaline urine and diuresis decrease), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, reduction of nitrogen production, diminution of urine, retention of urine, albuminuria, reduction of nitrogen production, decrease in azoteronephritis, polyuria, retention of urine, albuminuria, reduction of nitrogenous, urinary, recurrent, urinary retention itching, urticaria, skin rash, drug fever, petechiae, angioedema, shortness of breath, eosinophilia, vasculitis, erythema nodosum, multiforme exudative erythema (including Stevens-Johnson syndrome), Sical epidermal necrolysis (Lyell's syndrome). From the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia. From the laboratory indicators: hypoprothrombinemia, increased activity of hepatic transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, unsetting, unsetting, unsetting, unsetting, unsettled superinfections (candidiasis, pseudomembranous colitis), flushing, photosensitivity.
Overdose
Symptoms: in cases of acute overdose, symptoms of reversible damage to the urinary system will prevail, seizures are possible. Treatment: induction of vomiting, gastric lavage. Symptomatic, supportive therapy (including adequate hydration of the body). There is no specific antidote. Using hemo- or peritoneal dialysis, tinidazole can be completely eliminated from the body, and ciprofloxacin - only slightly (less than 10%).
Interaction with other drugs
TsiproletA enhances the effect of indirect anticoagulants. To reduce the risk of bleeding, the dose of CiproletA is reduced by 50%. Enhances the effect of ethanol (disulfiram-like reactions). Phenobarbital speeds up the metabolism of tinidazole. It is not recommended to prescribe TsiproletA concurrently with ethionamide. / 2 theophylline and other xanthines, incl. caffeine, oral hypoglycemic drugs, indirect anticoagulants, helps to reduce the prothrombin index. Amplifies the nephrotoxic effect of cyclosporine, an increase in serum creatinine is noted, in such patients, this indicator should be monitored 2 times a week. Oral administration with iron-containing drugs, sucralfate and antacid drugs containing Mg2 +, Ca2 +, Al3 +, with didanosine leads to a decrease in the absorption of ciprofloxacin.Therefore, CiproletA should be prescribed 1-2 hours before or 4 hours after taking these medicines. When used simultaneously with NSAIDs (excluding acetylsalicylic acid), the risk of seizures increases. means leads to a slower elimination (up to 50%) and an increase in plasma concentration of ciprofloxacin. Ciprofloxacin increases Cmax 7 times (from 4 to 21 times) and AUC of tizanidine, which increases the risk of pronounced a decrease in blood pressure and sonlivosti.TsiproletA compatible with sulfonamides and antibiotics (beta-lactam antibiotics, aminoglycosides, erythromycin, rifampin, cephalosporins), the combination of which is usually observed synergism.
special instructions
Should consider the possibility of cross-allergic reactions. Patients with hypersensitivity to other imidazole derivatives may develop cross-sensitivity to tinidazole; The development of a cross-allergic reaction to ciprofloxacin is also possible in patients with hypersensitivity to other fluoroquinolone derivatives. During treatment, it is recommended to avoid contact with direct sunlight. In the event of photosensitivity reactions, the use of the drug should be immediately discontinued. Ethanol is not recommended during the treatment period (the risk of disulfiram-like reactions on the background of tinidazole, which is part of the drug). To avoid crystalluria, the recommended daily dose should not be exceeded; reactions of urine. The drug causes dark staining of urine, which has no clinical significance. Patients with epilepsy, history of convulsions, Sudden diseases and organic lesions of the brain, due to the threat of adverse reactions from the CNS, the drug should be prescribed only for health reasons. If severe or prolonged diarrhea occurs during or after treatment, diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and administration appropriate treatment. In case of pain in the tendons or at the manifestation of the first signs of tendovaginitis, treatmentshould be stopped. When treating for more than 6 days, the picture of peripheral blood should be monitored. Influence on the ability to drive vehicles and control mechanisms. During treatment, the patient should refrain from practicing potentially hazardous activities that require increased concentration and psychomotor reactions.