Kombiflox tablets p / o 500mg + 200mg, No. 20

• mixed bacterial infections caused by sensitive gram-positive and gram-negative microorganisms, in association with anaerobic microorganisms and / or protozoa;

• infectious and inflammatory diseases of the abdominal and biliary tract, kidneys (pyelonephritis), lower urinary tract (cystitis, urethritis), genitals and pelvic organs (endometritis, salpingitis, oophoritis, cervicitis, parametritis, prostatitis, colpitis, orchitis, epididymitis) ...

Inside, 1 hour before meals or 2 hours after meals, drinking plenty of water. Do not crush, chew, or break the tablet.

The recommended dose is 1 tablet 2 times a day for 7-10 days.

Dosing regimen for chronic renal failure (calculation of the dose of ofloxacin): with CC 50-20 ml / min - 200 mg 1 time every 24 hours, with CC less than 20 ml / min, with hemodialysis, peritoneal dialysis - 200 mg 1 time every 48 hours.

In liver failure, the maximum daily dose is 2 tablets (400 mg of ofloxacin).

Film-coated tablets of orange color, capsular, with a score line on one side; at the break - the mass of a yellowish-creamy tablet.

1 tab.

ornidazole 500 mg

ofloxacin 200 mg

Excipients: microcrystalline cellulose 238 mg, sodium carboxymethyl starch 15 mg, croscarmellose sodium 10 mg, colloidal silicon dioxide 10 mg, talc 9 mg, magnesium stearate 12 mg, hypromellose 3.5 mg, quinoline yellow dye 0.1 mg.

• epilepsy (including history);

• lowering the seizure threshold (including after traumatic brain injury, stroke or inflammatory processes in the central nervous system;

• damage to the tendons with previous treatment with fluoroquinolones;

• age under 18;

• pregnancy;

• lactation period;

• hypersensitivity to ofloxacin, ornidazole, other fluoroquinolones and imidazole derivatives, drug components.

With care: atherosclerosis of cerebral vessels, cerebrovascular accident (in history), chronic renal failure, liver disease, liver failure, organic diseases of the central nervous system (including multiple sclerosis), predisposition to convulsive reactions, myasthenia gravis, hepatic porphyria, deficiency glucose-6-phosphate dehydrogenase, diabetes mellitus, congenital lengthening of the QT interval, heart disease (heart failure, myocardial infarction, bradycardia), psychosis and other mental disorders in history; simultaneous administration of drugs that prolong the QT interval (antiarrhythmic classes IA and III, tricyclic and tetracyclic antidepressants, antipsychotics, macrolides, antifungal, some antihistamines, including astemizole, terfenadine, ebastine),drugs for general anesthesia from the group of barbiturates, drugs that lower blood pressure; electrolyte imbalance (eg, hypokalemia, hypomagnesemia), old age, alcoholism

pharmachologic effect

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

Ornidazole is an antiprotozoal and antimicrobial agent derived from 5-nitroimidazole. The mechanism of action consists in the biochemical reduction of the 5-nitro group of ornidazole by intracellular transport proteins of anaerobic bacteria and protozoa. The reduced 5-nitro group of ornidazole interacts with DNA cells of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active against Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, as well as anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Clostridium spp. Aerobic microorganisms are not sensitive to ornidazole.

Ofloxacin is a broad-spectrum antimicrobial agent from the group of fluoroquinolones; it acts on the bacterial enzyme DNA gyrase, which provides supercoiling, etc. stability of bacterial DNA (destabilization of DNA strands leads to their death). It has a bactericidal effect.

The antimicrobial spectrum includes gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive), Staphylococcus epidermidis (methicillin-sensitive), Staphylococcus saprophyticus, Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes

Gram-negative aerobes: Acinetobacter calcoaceticus, Bordetella pertussis, Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella vulriae, Klebsiella oxytoca, vulrisella vulrae, Klebsiella oxyella Morgana , Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa (rapidly developing resistance), Serratia marcescens.

Anaerobes: Clostridium perfringens.

Others: Chlamydia trachomatis, Chlamydia pneumoniae, Gardnerella vaginalis, Legionella pneumophila, Mycoplasma hominis, Mycoplasma pneumoniae, Ureaplasma urealyticum.

In most cases, insensitive: Nocardia asteroides, anaerobic bacteria (including Bacteroides spp., Peptococcus spp., Peptostreptococcus spp., Eubacterium spp., Fusobacterium spp., Clostridium difficile), Enterococcus nonccus spp., Most spp. acts on Treponema pallidum.

Pharmacokinetics

Suction:

Both ofloxacin and ornidazole are well absorbed in the gastrointestinal tract after oral administration. Bioavailability - 90% (ornidazole) - 95% (ofloxacin). Communication with plasma proteins - 13% (ornidazole) - 25% (ofloxacin). TCmax - 1-2 hours, for ornidazole - 3 hours.

Distribution:

Ofloxacin: apparent volume of distribution - 100 liters. Distribution: cells (leukocytes, alveolar macrophages), skin, soft tissues, bones, abdominal and pelvic organs, respiratory system, urine, saliva, bile, prostate secretion; well penetrates the BBB, placental barrier, secreted with breast milk. Penetrates into the cerebrospinal fluid - 14-60%.

Ornidazole: penetrates into most tissues, passes through the BBB and the placenta, and enters breast milk.

Metabolism and excretion:

Ofloxacin: metabolized in the liver (about 5%) to form N-oxidofloxacin and dimethylofloxacin. T1 / 2 - 4.5-7 hours (regardless of dose). It is excreted by the kidneys - 75-90% (unchanged), about 4% - with bile. Extrarenal clearance is less than 20%. After a single dose of 200 mg in the urine, it is detected within 20-24 hours. In renal / hepatic insufficiency, excretion may slow down. Does not cumulate. Hemodialysis removes 10-30% of the drug.

Ornidazole: metabolized in the liver by hydroxylation, oxidation and glucuronidation. T1 / 2 - 12-14 hours. It is excreted in the form of metabolites (60-70%) and unchanged (4%) by the kidneys and intestines (20-25%), cumulates.

Side effect

From the digestive system: gastralgia, decreased appetite, nausea, vomiting, diarrhea, constipation, flatulence, abdominal pain, increased activity of liver transaminases, hyperbilirubinemia, cholestatic jaundice, pseudomembranous colitis, dryness of the oral mucosa, colitis (incl. including hemorrhagic), hepatitis.

From the nervous system: headache, dizziness, insomnia, nervousness, uncertainty of movements, tremor, convulsions, numbness and paresthesia of the extremities, intense dreams, 'nightmares', anxiety, arousal, phobias, depression, confusion, hallucinations, increased intracranial pressure, insomnia, nervousness, drowsiness, epileptic seizures, extrapyramidal disorders, psychotic reactions with suicidal tendencies, sensory or sensory-motor peripheral neuropathy, impaired coordination of movement, temporary loss of consciousness.

From the musculoskeletal system: tendonitis, myalgia, arthralgia, tendosynovitis, tendon rupture, limb pain, muscle stiffness, rhabdomyolysis, muscle weakness.

From the senses: color perception disturbance, diplopia, taste disturbances, perversion of taste sensations, disturbances of smell, hearing and balance.

From the side of the cardiovascular system: tachycardia, increase or decrease in blood pressure, collapse, prolongation of the QT interval, ventricular arrhythmia, incl. arrhythmia ventricular tachysystolic type 'pirouette'.

Allergic reactions: skin rash, itching, urticaria, allergic pneumonitis, allergic nephritis, eosinophilia, fever, angioedema, bronchospasm; exudative erythema multiforme (including Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome), photosensitivity, vasculitis, anaphylactic shock, itching of the external genital organs in women.

On the part of the skin: punctate hemorrhages (petechiae), bullous hemorrhagic dermatitis, papular rash with a crust, indicating vascular lesions (vasculitis).

From the side of hematopoiesis: leukopenia, agranulocytosis, anemia (including aplastic and hemolytic), thrombocytopenia, pancytopenia.

From the urinary system: acute interstitial nephritis, impaired renal function, hypercreatininemia, increased urea concentration, dysuria, urinary retention, acute renal failure.

Others: intestinal dysbiosis, superinfection, hypoglycemia (in patients with diabetes mellitus), vaginitis, chest pain, fatigue, asthenia, general weakness, photosensitivity, vaginal discharge, nosebleeds, thirst, weight loss, pharyngitis, rhinitis, dry cough, acute attack of porphyria (in patients with porphyria).

Application during pregnancy and lactation

The use of the drug during pregnancy and lactation is contraindicated. If necessary, the use of the drug during lactation should stop breastfeeding.

Application for violations of liver function

In patients with impaired liver function, it is necessary to monitor the concentration of ofloxacin in plasma.

Application for impaired renal function

In patients with impaired renal function, it is necessary to control the plasma concentration of ofloxacin.

Application in children

Contraindicated under 18 years of age.

Use in elderly patients

With caution in old age.

special instructions

It is not recommended to be exposed to sunlight, ultraviolet rays (mercury-quartz lamps, solarium).

To prevent hyperconcentration of urine and subsequent crystalluria, it is recommended to carry out adequate hydration during treatment.

In case of side effects from the central nervous system, allergic reactions, pseudomembranous colitis, the development of symptoms of peripheral neuropathy, the drug should be discontinued.

Rarely occurring tendonitis can rupture tendons (mainly the Achilles tendon), especially in older patients. In case of signs of tendinitis, it is necessary to immediately stop treatment, immobilize the Achilles tendon and consult an orthopedist. Ethanol should not be consumed during the treatment period.

When using the drug, women are not recommended to use hygienic tampons due to the increased risk of developing thrush.

Against the background of treatment, a worsening of the course of myasthenia gravis, an increase in porphyria attacks in predisposed patients is possible.

With simultaneous use with drugs that prolong the QT interval, antiarrhythmic classes IA and III, tricyclic and tetracyclic antidepressants, antipsychotics, macrolides, antifungals, some antihistamines, incl. astemizole, terfenadine, ebastine) systematic ECG monitoring is required.

May lead to false negative results in bacteriological diagnosis of tuberculosis (prevents the release of Mycobacterium tuberculosis).

In patients with impaired liver or kidney function, it is necessary to monitor the concentration of ofloxacin in plasma. In severe renal failure, the risk of developing toxic effects increases (a decreasing dose adjustment is required).

When using the drug, both while taking it and 2-3 weeks after stopping treatment, it is possible to develop diarrhea caused by Clistridium difficile (pseudomembranous colitis). In mild cases, it is sufficient to discontinue treatment and use ion-exchange resins (cholestyramine, colestipol), in severe cases, it is shown to replace the loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole.

Do not use drugs that inhibit intestinal motility.

Influence on the ability to drive vehicles and engage in other potentially hazardous activities.

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: dizziness, confusion, lethargy, disorientation, drowsiness, vomiting, epileptiform seizures, depression, peripheral neuritis.

Treatment: gastric lavage, symptomatic therapy (diazepam - for convulsions).

Drug interactions

Ofloxacin:

Reduces the clearance of theophylline by 25% (with simultaneous use, the dose of theophylline should be reduced).

Increases the concentration of glibenclamide in plasma. Increases the serum concentration of cyclosporine.

Cimetidine, furosemide, methotrexate and drugs (drugs) that block tubular secretion increase the concentration of ofloxacin in the blood plasma. When taken simultaneously with indirect anticoagulants (coumarin derivatives, including warfarin), it is necessary to monitor the blood coagulation system. When administered with non-steroidal anti-inflammatory drugs, derivatives of nitroimidazole and methylxanthines, the risk of neurotoxic effects, including seizures, increases.

With simultaneous administration with glucocorticosteroids, the risk of tendon rupture increases, especially in the elderly.

When administered with drugs that alkalize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases. With simultaneous administration with hypoglycemic agents, both hypo- and hyperglycemia are possible, in connection with which it is necessary to control the concentration of glucose in the blood plasma.

With simultaneous use with drugs that prolong the QT interval, antiarrhythmic classes IA and III, tricyclic and tetracyclic antidepressants, antipsychotics, macrolides, antifungals, some antihistamines, incl. astemizole, terfenadine, ebastine) prolongation of the QT interval is possible. Food products, antacids containing ions of aluminum, calcium, magnesium or iron salts, reduce the absorption of ofloxacin, forming insoluble complexes (the time interval between the appointment of these drugs should be at least 2 hours).

Ornidazole:

Strengthens the effect of indirect anticoagulants of the coumarin series, lengthens the muscle relaxant effect of vecuronium bromide.

Compatible with ethanol (does not inhibit acetaldehyde dehydrogenase), unlike other imidazole derivatives (metronidazole).