Tsiprolet A tablets 500 + 600mg, No. 10

Mixed bacterial infections caused by sensitive gram-positive and gram-negative microorganisms, in association with anaerobic microorganisms and / or protozoa:

• respiratory tract infections (acute and chronic (in the acute stage) bronchitis, pneumonia, bronchiectasis);

• otitis media infections (otitis media, sinusitis, frontal sinusitis, mastoiditis, tonsillitis, pharyngitis);

• oral cavity infections (acute ulcerative gingivitis, periodontitis, periostitis);

• infections of the kidneys and urinary tract (cystitis, pyelonephritis);

• infections of the pelvic organs and genitals (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.

The drug is administered orally, 1 hour before meals or 2 hours after meals. The recommended dose is 1 tab. 2 times / day for 5-10 days.

The tablets should be taken with plenty of water. Do not crush, chew, or break the tablet.

Film-coated tablets from white to almost white, oval in shape, with a dividing line on one side and smooth on the other; cross-sectional view - from white to light yellow.

1 tab.

ciprofloxacin hydrochloride monohydrate 582.285 mg,

which corresponds to the content of ciprofloxacin 500 mg

tinidazole 600 mg

Excipients: corn starch - 35 mg, croscarmellose sodium - 27.476 mg, microcrystalline cellulose - 20.33 mg, sodium carboxymethyl starch (type A) - 5 mg, colloidal silicon dioxide - 3.952 mg, talc - 8.952 mg, magnesium stearate - 7 mg.

• Diseases of the blood (in history);

• oppression of bone marrow hematopoiesis;

• organic diseases of the central nervous system;

• pregnancy;

• lactation period (breastfeeding);

• simultaneous reception with tizanidine (risk of a pronounced decrease in blood pressure, drowsiness);

• acute porphyria;

• children and adolescents up to 18 years old;

• hypersensitivity to drug components;

• hypersensitivity to fluoroquinolone or imidazole derivatives.

  The drug should be used with caution in severe atherosclerosis of cerebral vessels, impaired cerebral circulation, mental illness, epilepsy, indications of a history of convulsions, with severe renal and / or hepatic failure, in elderly patients.

pharmachologic effect

Combined drug, the action of which is due to the components that make up its composition.

Ciprofloxacin - a broad-spectrum antimicrobial agent, a fluoroquinolone derivative, inhibits bacterial DNA gyrase (topoisomerases II and IV, which are 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 the cell wall and membranes) and rapid death of the bacterial cell.

It acts bactericidal on gram-negative organisms during dormancy 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 cells of a macroorganism is explained by the absence of DNA gyrase in them. While taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of gyrase inhibitors, which makes it highly effective against bacteria resistant to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin is active against gram-negative aerobic bacteria: Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvearda, Edwardsiella. 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: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus),Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Most methicillin-resistant staphylococci are also 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 enzymes that inactivate it.

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

Tinidazole is an antiprotozoal and antimicrobial agent, an imidazole derivative. Active against Trichomonas vaginalis, Entamoeba histolitica, Lamblia, as well as pathogens 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 DNA structure.

Pharmacokinetics

Suction

Both ciprofloxacin and tinidazole are well absorbed from the gastrointestinal tract after oral administration. Food intake slows down absorption, but does not change the Cmax value and bioavailability.

Distribution

Ciprofloxacin

Bioavailability - 50-85%, Vd - 2-3.5 l / kg, binding to plasma proteins - 20-40%, Tmax after oral administration - 60-90 minutes, Cmax after oral administration at a dose of 500 mg - 0.2 ?g / ml.

Tinidazole

Bioavailability - 100%, binding to plasma proteins - 12%, Tmax after oral administration - 2 hours, Cmax after oral administration at a dose of 500 mg - 47.7 ?g / ml.

Metabolism and excretion

Tinidazole enters the cerebrospinal fluid at a concentration equal to that in plasma and is reabsorbed in the renal tubules. T1 / 2 - 12-14 hours. Tinidazole is metabolized in the liver with the participation of the cytochrome P450 enzyme system (CYP3A4). About 50% is excreted in the bile, 25% - by the kidneys, 12% - in the form of metabolites. It undergoes reabsorption in the renal tubules.

Ciprofloxacin penetrates well into fluids and body tissues (excluding tissue rich in fats, such as nerve 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, 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. 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 serum, and with inflamed membranes - 14-37%. Ciprofloxacin also penetrates well into the eye fluid, bronchial secretions, pleura, peritoneum,lymph through the placenta. The concentration of ciprofloxacin in neutrophils is 2-7 times higher than in blood plasma. The activity decreases slightly at pH values ??less than 6. It is metabolized in the liver (15-30%) with the formation of low-active metabolites (diethylcyprofloxacin, sulfocyprofloxacin, oxocyprofloxacin, formylcyprofloxacin).

T1 / 2 - about 4 hours. It is excreted mainly by the kidneys by tubular filtration and tubular 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.

In ciprofloxacin in chronic renal failure, T1 / 2 increases up to 12 hours. In chronic renal failure (CC 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 the metabolism of the drug and its excretion through the gastrointestinal tract.

Side effect

From the digestive system: decreased appetite, dryness of the oral mucosa, 'metallic' taste in the mouth, nausea, vomiting, diarrhea, abdominal pain, flatulence, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis.

From the side of the central nervous system and peripheral nervous system: headache, dizziness, increased fatigue, impaired coordination of movements (including locomotor ataxia), dysarthria, peripheral neuropathy; rarely - convulsions, weakness, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (anomaly in the perception of pain), increased intracranial pressure, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions, migraine, fainting, cerebral artery thrombosis , increased sweating.

From the senses: disturbances in taste and smell, visual impairment (diplopia, change in color perception), tinnitus, hearing loss.

From the side of the cardiovascular system: tachycardia, arrhythmia, decreased blood pressure.

From the side of hematopoiesis: leukopenia, granulocytopenia, anemia (including hemolytic), thrombocytopenia, leukocytosis, thrombocytosis.

From the urinary system: hematuria, crystalluria (with an alkaline urine reaction and decreased urine output), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, decreased nitrogen excretion function of the kidneys, interstitial nephritis.

Allergic reactions: pruritus, urticaria, skin rash, drug fever, petechiae, angioedema, shortness of breath, eosinophilia, vasculitis, erythema nodosum, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis syndrome ...

From the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia.

On the part of laboratory parameters: hypoprothrombinemia, increased activity of hepatic transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

Others: asthenia, superinfection (candidiasis, pseudomembranous colitis), flushing, photosensitivity.

Application during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Tinidazole and ciprofloxacin are excreted in breast milk, therefore, breastfeeding should be discontinued for the period of drug treatment, since tinidazole may have mutagenic and carcinogenic effects.

Application for violations of liver function

The drug should be used with caution in severe liver failure.

Application for impaired renal function

The drug should be used with caution in severe renal failure.

Application in children

Contraindication: children and adolescents up to 18 years of age.

Use in elderly patients

The drug should be used with caution in elderly patients.

special instructions

Consideration should be given to the possibility of cross-allergic reactions. In patients with hypersensitivity to other imidazole derivatives, cross-sensitivity to tinidazole may also develop; 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. If photosensitization reactions occur, the drug should be discontinued immediately.

During the period of treatment, it is not recommended to take ethanol (the risk of developing disulfiram-like reactions against the background of tinidazole, which is part of the drug).

In order to avoid the development of crystalluria, the recommended daily dose must not be exceeded; sufficient fluid intake and maintenance of the acidic reaction of urine are also necessary.

The drug causes dark coloration of urine, which has no clinical significance.

Patients with epilepsy, a history of seizures, vascular diseases and organic brain lesions, due to the threat of adverse reactions from the central nervous system, the drug should be prescribed only for health reasons.

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

If pain in the tendons appears or when the first signs of tendovaginitis appear, treatment should be discontinued.

When treating for more than 6 days, the peripheral blood picture should be monitored.

Influence on the ability to drive vehicles and mechanisms.

During treatment, the patient should refrain from engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: in cases of acute overdose, symptoms of reversible damage to the urinary system will prevail, convulsions are possible.

Treatment: induction of vomiting, gastric lavage. Symptomatic, supportive therapy (including adequate hydration of the body). There is no specific antidote. With the help of hemo- or peritoneal dialysis, tinidazole can be completely eliminated from the body, and ciprofloxacin - slightly (less than 10%).

Drug interactions

Effects due to tinidazole

TsiproletЃA enhances the effect of indirect anticoagulants. To reduce the risk of bleeding, the dose of CiproletЃA is reduced by 50%.

Enhances the effect of ethanol (disulfiram-like reactions).

Phenobarbital accelerates the metabolism of tinidazole.

TsiproletЃA is not recommended to be administered concurrently with ethionamide.

Effects due to ciprofloxacin

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and lengthens T1 / 2 of theophylline and other xanthines, incl. caffeine, oral hypoglycemic drugs, indirect anticoagulants, helps to reduce the prothrombin index.

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

Oral administration together with iron-containing drugs, sucralfate and antacid drugs containing Mg2 +, Ca2 +, Al3 +, with didanosine leads to a decrease in the absorption of ciprofloxacin. Therefore, TsiproletЃA should be prescribed 1-2 hours before or 4 hours after taking these drugs.

With simultaneous use with NSAIDs (excluding acetylsalicylic acid), the risk of seizures increases.

Metoclopramide accelerates the absorption of ciprofloxacin, which leads to a decrease in Tmax.

The joint appointment of uricosuric drugs leads to a slowdown in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

Ciprofloxacin increases the Cmax by 7 times (from 4 to 21 times) and the AUC of tizanidine, which increases the risk of a pronounced decrease in blood pressure and drowsiness.

CiproletЃA is compatible with sulfonamides and antibiotics (beta-lactam antibiotics, aminoglycosides, erythromycin, rifampicin, cephalosporins), when combined with which synergism is usually observed.