Ciprolet A, 600 mg+500 mg 10 pcs

Pharmacological action – antimicrobial, antiprotozoal.
Pharmacodynamics

A combined drug, the action of which is due to the components in its composition.

Tinidazole is an antiprotozoal and antimicrobial agent, imidazole derivative, effective against Trichomonas vaginalis, Entamoeba histolytica, 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 drug, it penetrates inside trichomonads and anaerobic microorganisms, where it is reduced by nitroreductase, inhibits synthesis and damages DNA structure.

Ciprofloxacin is an antimicrobial agent of broad spectrum activity, derivative of fluoroquinolone, inhibits bacterial DNA-giase (topoisomerases II and IV, responsible for the process of superspiralization of chromosomal DNA around the nuclear RNA, which is required for reading genetic information), inhibits DNA synthesis, growth and division of bacteria, causes evident morphological changes (including cell wall and membrane membrane).cell wall and membranes) and rapid death of the bacterial cell.

It is bactericidal on Gram-negative organisms during resting and dividing (as it affects not only DNA-giase, but also causes lysis of cell wall), on Gram-positive microorganisms – only during dividing. Low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them. Against the background of ciprofloxacin use there is no parallel development of resistance to other antibiotics which do not belong to gyrase inhibitor group which makes it highly effective against bacteria resistant to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin is sensitive to Gram-negative aerobic bacteria: Enterobacteriaceae (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: 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 very slowly because, on the one hand, after the action of ciprofloxacin there are practically no persistent microorganisms, and on the other hand, bacterial cells have no enzymes that inactivate it. Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides are resistant to the drug. Ineffective against Treponema pallidum.

Pharmacokinetics

Intake

All ciprofloxacin and tinidazole are well absorbed in the GI tract after oral administration. Food intake slows absorption but does not change the maximum concentration and bioavailability.

Distribution

Tinidazole. Bioavailability – 100%, binding to plasma proteins – 12%, Tmax after oral administration – 2 hours, Cmax after 500 mg oral administration – 47,7 µg/ml.

Ciprofloxacin. Bioavailability – 50-85%, Vd – 2-3.5 l/kg, binding to plasma proteins – 20-40%, Tmax after oral administration – 60-90 min, Cmax after 500 mg – 0.2 µg/ml.

Metabolism and excretion

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

Ciprofloxacin penetrates well into the body fluids and tissues (excluding fat-rich tissue, such as nerve tissue). Concentrations in tissues are 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gallbladder, bile, intestine, abdominal and pelvic organs, uterus, seminal fluid, prostatic tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary tract, lung tissue, bronchial secretion, bone tissue, muscles, synovial fluid and joint cartilage, peritoneal fluid, skin. It penetrates into the cerebrospinal fluid in small amounts, where its concentration, in the absence of cerebral membrane inflammation, is 6-10% of serum fluid, and in the case of inflammation – 14-37%.

Ciprofloxacin also penetrates well into the ocular fluid, bronchial secretion, pleura, peritoneum, lymph, and through the placenta. The concentration of ciprofloxacin in neutrophils is 2-7 times higher than in blood plasma. Activity decreases slightly at pH values less than 6. It is metabolized in the liver (15-30%) to form inactive metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin). T1/2 is about 4 hours. It is eliminated mainly by the kidneys by tubular filtration and tubular secretion unchanged (40-50%) and as metabolites (15%), the rest – through the gastrointestinal tract. A small amount is excreted with breast milk. Renal Cl is 3-5 ml/min/kg; total Cl is 8-10 ml/min/kg.

In special cases

The pharmacokinetic parameters of tinidazole in patients with CKD (creatinine Cl above 22 ml/min) do not differ from those in healthy subjects.

The T1/2 of ciprofloxacin in CPN is increased up to 12 hours. In CKD (creatinine Cl above 20 ml/min) the percentage excreted through the kidneys.

Indications

Otitis, Periodontitis, Bronchitis, Urinary tract infections, Prostatitis, Pharyngitis, Biliary tract infections, Osteomyelitis, Tonsillitis, Intestinal infections, Purulent wounds, Adnexitis, Pneumonia, Bedsores, Skin infections, Sinusitis.p> Mixed bacterial infections caused by susceptible gram-positive and gram-negative microorganisms in association with anaerobic microorganisms and/or protozoa:

• respiratory tract infections (acute and chronic (acute stage) bronchitis, pneumonia, bronchiectatic disease);
• infections of the ENT (otitis media, maxillary sinusitis, sinusitis, mastoiditis, tonsillitis, pharyngitis);
• infections of the oral cavity (acute ulcerative gingivitis, periodontitis, periostitis)
• infections of the kidneys and urinary tract (cystitis, pyelonephritis)Infections of the pelvic and genital organs (prostatitis, adnexitis, salpingitis, oophritis, endometritis, tubular abscess, penile peritonitis);
• intra-abdominal infections (GI infections, biliary tract, intra-abdominal abscesses);
• Skin and soft tissue infections (infected ulcers, wounds, burns, abscesses, phlegmon, skin ulcers in diabetic foot syndrome, bedsores);
• bone and joint infections (osteomyelitis, septic arthritis);
• postoperative infections.

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Active ingredient

Tinidazole, Ciprofloxacin

Composition

1 Filmed film-coated tablet:

active ingredients:

ciprofloxacin hydrochloride monohydrate – 582.285 mg (equivalent to 500 mg of ciprofloxacin),

tinidazole – 600.00 mg,

excipients: Corn starch – 35 mg; croscarmellose sodium – 27.476 mg; MCC – 5 mg; sodium carboxymethyl starch (type A) – 5 mg; colloidal silica – 3.952 mg; talc – 8.952 mg; magnesium stearate – 7 mg,

film coating: Hypromellose (6 cps), 21.21 mg; sorbic acid, 0.2095 mg; titanium dioxide, 1 mg; talc, 4.01 mg; macrogol 6000, 4.01 mg; polysorbate 80, 0.2095 mg; dimethicone, 0.295 mg; Sunset Yellow dye (E110), 9.047 mg.

How to take, the dosage

Overly, 1 h before or 2 h after a meal with plenty of water. The tablet should not be crushed, chewed or crushed.

The recommended dose is 1 tablet 2 times daily for 5-10 days.

Interaction

Tinidazole-induced effects. It enhances the effect of indirect anticoagulants. To reduce the risk of bleeding, the dose of the drug Ciprolet®A should be reduced by 50%. It enhances the effect of ethanol (disulfiram-like reactions). Phenobarbital accelerates metabolism of Tinidazole. It is not recommended to use Ciprolet® A with ethionamide.

The effects caused by ciprofloxacin. Due to the decrease of microsomal oxidation processes in hepatocytes it increases the concentration and prolongs T1/2 of theophylline and other xanthines including caffeine, oral hypoglycemic drugs, indirect anticoagulants and decreases prothrombin index. It increases nephrotoxic effect of cyclosporine; an increase of serum creatinine is noted; this index should be controlled 2 times a week in these patients.

The drug Ciprolet®A is compatible with sulfonamides and antibiotics (β-lactam antibiotics, aminoglycosides, erythromycin, rifampicin, cephalosporins) with which synergism is usually observed.

Special Instructions

The possibility of cross-allergic reactions should be considered. Patients with hypersensitivity to other imidazole derivatives may also develop cross-sensitivity to tinidazole; development of cross-allergic reaction to ciprofloxacin is also possible in patients with hypersensitivity to other fluoroquinolone derivatives.

At the time of treatment it is recommended to avoid contact with direct sunlight. If photosensitization reactions occur, the drug should be discontinued immediately.

To avoid taking ethanol during treatment (risk of disulfiram-like reactions with tinidazole, a component of the drug).

In order to avoid the development of crystalluria, the recommended daily dose should not be exceeded, and adequate fluid intake and maintenance of an acidic urine reaction are also necessary. Causes dark staining of the urine, which has no clinical significance.

Patients with epilepsy, history of seizures, vascular disease and organic brain damage, due to the risk of CNS adverse reactions, the drug should be prescribed only for vital signs.

In case of severe and prolonged diarrhea during or after treatment the diagnosis of pseudomembranous colitis should be excluded, which requires immediate withdrawal of the drug and appropriate treatment.

In case of tendon pain or the first signs of tendovaginitis, treatment should be discontinued.

The peripheral blood count should be monitored during treatment for more than 6 days.

Impact on the ability to drive a car or perform work requiring increased speed of physical and mental reactions. During treatment, refrain from engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

• Hypersensitivity (including. to fluoroquinolone or imidazole derivatives;
• blood disorders (in anamnesis);
• inhibition of medullary hematopoiesis;
• organic CNS disorders;
• pregnancy;

pregnancypregnancy;

• lactation period;
• concomitant use with tizanidine (risk of marked BP decrease, drowsiness);
• acute porphyria;
• children under 18 years of age.

With caution: Severe atherosclerosis of cerebral vessels;

disorder of cerebral circulation;

psychiatric conditions; epilepsy; history of seizures;

serious renal and/or hepatic impairment;

older age.

Side effects

Digestive system disorders: decreased appetite, dry mouth, metallic taste in the mouth, nausea, vomiting, diarrhea, abdominal pain, flatulence, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis.

Nervous system disorders: headache, dizziness, increased fatigue, impaired coordination of movements (including locomotor ataxia), dysarthria, peripheral neuropathy; rarely – seizures, weakness, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (abnormal perception of pain), increased IOP, confusion, depression, hallucinations, and other manifestations of psychotic reactions, migraine, fainting states, cerebral artery thrombosis, increased sweating.

Sense organs: disorders of taste and smell, visual impairment (diplopia, change in color perception), tinnitus, decreased hearing.

Systemic system disorders: tachycardia, arrhythmia, decreased blood pressure.

Hematopoietic disorders: leukopenia, granulocytopenia, anemia (including hemolytic), thrombocytopenia, leukocytosis, thrombocytosis.

Urinary system disorders: hematuria, crystalluria (with alkaline reaction of urine and decreased diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, decreased renal nitrogen excretion function, interstitial nephritis.

Allergic reactions: skin itching, urticaria, skin rash, drug fever, petechiae, angioedema, dyspnea, eosinophilia, photosensitization, vasculitis, erythema nodosa, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome).

In laboratory parameters: hypoprothrombinemia, increased liver transaminases and alkaline phosphatase activity, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

Others: arthralgia, arthritis, tendovaginitis, tendon tears, asthenia, myalgia, superinfections (candidiasis, pseudomembranous colitis), flushes of blood to the face.

Overdose

Symptoms: in cases of acute overdose symptoms of reversible damage of 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. With hemo- or peritoneal dialysis tinidazole can be completely eliminated from the body, and ciprofloxacin – slightly (<10%).

Pregnancy use

Tinidazole and ciprofloxacin are excreted into breast milk, so you should stop breast-feeding during treatment with the drug, because tinidazole may have mutagenic and carcinogenic effects.

Similarities

Cifran ST