Ofloksatsin-Tev

General characteristics. Structure:

Active agent mg ofloxacin 200,0/400,0;
excipients: lactoses monohydrate of 105,6/211,2 mg, starch of prezhelatinizirovanny 54,0/108,0 mg, gipromelloza of 20,0/40,0 mg, croscarmellose sodium 16,0/32,0 of mg, silicon dioxide of colloid 0,4/0,8 mg, magnesium mg stearate 4,0/8,0, cover of Opadray the II white 33G28707 (gipromelloza-6sr 6,00/9,60 mg, titanium E171 3,60/5,76 dioxide of mg, lactose monohydrate of 3,30/5,28 mg, macrogoal-3000 of 1,20/1,92 mg, mg triacetin 0,90/1,44).

Description
Tablets of 200 mg: white round biconvex tablets, film coated, with risky on both parties. On one party - an engraving of "FXN" on the one hand from risks and "200" - on the other hand from risks. On cross section - a kernel of white or almost white color.
Tablets of 400 mg: white oval biconvex tablets, film coated, with risky on one party and an engraving of "FXN" and "400" - on another. On cross section - a kernel of white or almost white color.

Pharmacological properties:

Pharmacodynamics. Bactericidal action of an ofloksatsin is connected with inhibition bacterial DNK-girazy that leads to destabilization of DNA of bacteria and death of bacterial cells.
Prevalence of the acquired resistance of separate species of bacteria to an ofloksatsin can vary in different geographical regions and at different times therefore very important existence of information on structure of local resistance, especially at treatment of heavy infections. If structure of local resistance such is that expediency of use of specific drug raises doubts, it is necessary to address for consultation microbiologists.
Ofloxacin possesses the wide range of antimicrobic action including the microorganisms steady against other antibiotics, including strains developing beta lactamelements.
Sensitive microorganisms: aerobic gram-positive microorganisms - Staphylococcus aureus (metitsillinchuvstvitelny), Staphylococcus epidermidis (metitsillinchuvstvitelny), Staphylococcus saprophyticus, Streptococcus pneumoniae (penitsillinchuvstvitelny), Streptococcus pyogenes; aerobic gram-negative microorganisms - Acinetobacter calcoaceticus, Bordetella pertussis, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa (quickly develops stability), Serratia marcescens; anaerobic microorganisms - Clostridium perfringens; other microorganisms - Chlamydia pneumoniae, Chlamydia trachomatis, Gardnerella vaginalis, Legionella pneumophila, Mycoplasma hominis, Mycoplasma pneumoniae, Ureaplasma urealyticum.
Are in most cases insensitive: Nocardia asteroids; anaerobic microorganisms - Bacteroides spp., Clostridium difficile, Eubacterium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Enterococcus spp., most Streptococcus spp.; does not affect Treponema pallidum.
The mechanism of bacterial resistance to an ofloksatsin is connected with one or several mutations of enzymes targets which are generally steady against other ftorkhinolona.

Pharmacokinetics. Absorption after intake bystry and full (about 95%). Bioavailability - 96%. About 25% of the entered dose contact proteins of a blood plasma. The maximum concentration (Cmax) = 2,6 mkg/ml is reached in 1 h after intake of 200 mg of drug. The seeming distribution volume - 100 l. Quickly gets and it is well distributed in many bodies, fabrics and liquids of an organism, gets in cells. Therapeutic the significant concentration exceeding concentration in a blood plasma are observed in intersticial fabric, saliva, a phlegm, lung tissue, a myocardium, bones, a mucous membrane and a wall of intestines, peritoneal liquid, pancreatic juice and tissue of a pancreas, tissue of a prostate gland, semen, bodies of female reproductive system, skin and hypodermic cellulose; gets into leukocytes and alveolar macrophages. Well gets through a blood-brain barrier, reaching therapeutic concentration, in high concentration gets through a gematoplatsentarny barrier, it is allocated with breast milk. 14-60% get into medullispinal liquid. About 5% of the entered dose are exposed to biotransformation in a liver. Main metabolites of an ofloksatsin: N-oxide and N-dimetilofloksatsin. The elimination half-life (F/4) is equal to 5,7-7 h and does not depend on the entered dose. At repeated introductions the cumulative effect is not expressed, plasma concentration increase slightly. Ofloxacin is removed preferential by kidneys in not changed look (80-90% of the entered dose), about 4% - with bile. Extrarenal clearance - 20%. After introduction in a dose of 200 mg the general clearance makes 258 ml/min. In insignificant quantities it is removed through intestines. At patients with a renal failure of T1/2 of an ofloksatsin increases; the general and renal clearance decrease in proportion. At a hemodialysis 10-30% of an ofloksatsin are removed. At a liver failure removal can be slowed down.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to an ofloksatsin, including:
• lower respiratory tracts (exacerbation of chronic bronchitis, pneumonia);
• kidneys and urinary tract, including pyelonephritis, urethritis;
• generative organs and bodies of a small pelvis, including, cervicitis, prostatitis;
• skin and soft tissues.

Route of administration and doses:

Inside. The dose of an ofloksatsin should be selected depending on type and weight of an infection, and also the general condition of the patient and function of a liver and kidneys. A pill is taken entirely, washing down with water, to or during food.
On 200-800 mg a day in 2 receptions through equal intervals of time. The dose to 400 mg a day can be accepted in one step, it is better in the first half of day.
Patients with a renal failure (KK less than 50 ml/min.) need correction of the mode of dosing depending on size KK.

KK                        Concentration of creatinine in       the Dose and frequency rate of introduction
                                  to plasma (mg/dl), / td>
20-50                                                  ml/min. 1,5-5,0 100-200 mg each 24 h
Less than 20                                  ml/min. Not less than 5,0 100 mg each 24 h or 200 mg 
or hemodialysis and                                                        each 48 h
peritoneal dialysis

After a hemodialysis or peritoneal dialysis introduction of additional doses is not required.
The clearance of creatinine can be calculated on the formulas given below.
For men: [the body weight (kg) x (140 - age (full years))] / [72 x concentration of creatinine in plasma (mg/dl)]
For women: 0,85 x KK men
At patients with heavy abnormal liver functions excretion of an ofloksatsin can be lowered. In such cases the daily dose of an ofloksatsin should not exceed 400 mg.
Dose adjustment is not required from patients of advanced age.
Duration of treatment is defined by sensitivity of the activator, weight of an infectious disease and the response to therapy. It is necessary to continue treatment at least 3 more days after full normalization of body temperature or after confirmation of an eradikation of the bacterial agent. Usually duration of treatment makes 7-10 days, except for treatment of gonorrhea, and should not exceed 2 months.

Features of use:

It is not necessary to appoint ofloxacin as drug of the first choice for treatment of the community-acquired pneumonia caused by Streptococcus pneumoniae and Mycoplasma spp., and the acute tonsillitis caused by Streptococcus pyogenes.
Development of superinfection due to growth of microorganisms, insensitive to an ofloksatsin, especially Enterococcus spp is possible. and Candida spp. In this case it is necessary to carry out sensitivity tests to antibiotics and to correct the scheme of treatment. At emergence in time or after treatment ofloksatsiny heavy and long diarrhea it is necessary to exclude a possibility of development of pseudomembranous colitis which confirmation demands drug withdrawal.
Ofloxacin inhibits Mycobacterium tuberculosis growth that can lead to false-negative results of bacteriological tests at patients with tuberculosis.
In spite of the fact that ofloxacin seldom causes a photosensitization, during treatment this drug recommends to avoid long influence of direct sunshine or artificial ultraviolet radiation (UFI) (a sunbed, treatment of UFI). For prevention of excess content of salts in urine and the subsequent crystalluria during treatment it is recommended to carry out adequate hydration.
Seldom arising tendinitis can lead to a rupture of sinews (preferential an Achilles tendon). The risk of a rupture of sinews increases at reception of ftorkhinolon against the background of reception of GKS. Tendinites develop at elderly patients more often. In case of signs of a tendinitis it is necessary to stop immediately treatment, to make an immobilization of an Achilles tendon and to consult at the orthopedist.
At use of an ofloksatsin of the woman should not use hygienic tampons in connection with the increased risk of development of the milkwoman.
At the patients predisposed to development of Bouveret's ventricular disease like "pirouette" or accepting the drugs extending QT interval and also for identification of disturbances of ventricular conductivity before treatment ofloksatsiny it is necessary to conduct a research of the electrocardiogram (ECG) and to regularly carry out monitoring of indicators of an ECG during treatment.
Lasting treatment more than 2 weeks it is necessary to carry out control of indicators of a blood count and biochemical indicators of blood.
During treatment it is impossible to use ethanol.
At simultaneous use with indirect anticoagulants it is necessary to exercise control of coagulant system of blood.
At simultaneous use with hypoglycemic drugs it is possible both hypo - and a hyperglycemia in this connection it is necessary to control concentration of glucose in a blood plasma.
At patients with a renal failure (KK less than 50 ml/min.), a heavy abnormal liver function dose adjustment of an ofloksatsin is necessary (see the section "Route of Administration and Doses").
At a disease of a liver it is necessary ofloksatsiny to define indicators of a functional condition of a liver before treatment, and also to carry out monitoring of these indicators during treatment.
At patients with abnormal liver functions or kidneys control of concentration of an ofloksatsin in plasma is necessary. At a heavy renal and liver failure the risk of development of toxic effects increases (the reducing dose adjustment is required).
Against the background of treatment ofloksatsiny deterioration in a current of a myasthenia of gravis and increase of attacks of a porphyria is possible.
At the patients receiving ftorkhinolona including ofloxacin, it was reported about development of touch and sensory-motor neuropathy which can have quick start. At emergence of symptoms of neuropathy treatment ofloksatsiny has to be stopped that promotes minimization of possible risk of development of irreversible states.
Drug Ofloksatsin-Tev should be used with care at the patients predisposed to development of spasms (patients with damage of the central nervous system (CNS) in the anamnesis, including disturbance of cerebral circulation, the patients accepting NPVP and also other drugs reducing a convulsive threshold of a brain such as theophylline) (see the section "Interaction with Other Medicines").
In case of side reactions from TsNS and allergic reactions drug change is necessary.
Influence on results of laboratory tests: at treatment ofloksatsiny obtaining false positive results when determining opiates and porphyrines in urine is possible.

Influence on ability to driving of the car and to control of mechanisms
During treatment ofloksatsiny it is necessary to be careful during the driving of transport and control of mechanisms in connection with a possibility of development of the side effects from a nervous system (dizziness, drowsiness) influencing ability to concentrate attention and speed of psychomotor reactions.

Side effects:

Frequency of development of side reactions is classified according to recommendations of World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - less than 0,01%, including separate messages.
From the alimentary system: often - nausea, vomiting, diarrhea, an abdominal pain; infrequently - a loss of appetite, a lock, a meteorism; seldom - increase in activity of "hepatic" transaminases, a hyperbilirubinemia, cholestatic jaundice, colitis (including hemorrhagic), dryness of a mucous membrane of an oral cavity; very seldom - hepatitis, pseudomembranous colitis.
From a nervous system: infrequently - a headache, dizziness, sleeplessness, concern, nervousness; seldom - "dreadful" dreams, intensive dreams, psychotic reactions, uneasiness, a condition of excitement, a phobia, a depression, confusion of consciousness, a hallucination, suicide attempts, drowsiness, a tremor, spasms, numbness and paresthesias of extremities, uncertainty of movements, increase in intracranial pressure; very seldom - extrapyramidal frustration, touch or sensory-motor neuropathy, peripheral neuropathy.
From sense bodys: infrequently - conjunctivitis; seldom - disturbance of color perception, a diplopia, disturbances of taste, sense of smell, balance; very seldom - a sonitus, a hearing disorder, including deafness in exceptional cases.
From a musculoskeletal system: very seldom - the tendinitis, mialgiya, muscular weakness at patients with a myasthenia, arthralgias, tendosinovit, a rupture of sinews, muscular and joint symptoms of a rabdomioliz, extremity pain.
From cardiovascular system: infrequently - a heart consciousness; seldom - heart failure, hypotonia; very seldom - ventricular arrhythmia, including Bouveret's ventricular disease like "pirouette", lengthening of an interval of QT, hypertensia.
From respiratory system: infrequently - dry cough, a nasopharyngitis; seldom - an asthma, a bronchospasm; unknown frequency - an allergic pneumonitis.
From skin and hypodermic fabrics: very seldom - petechias, violent hemorrhagic dermatitis, papular rash with a crust, testimonial of defeat of vessels (vasculitis).
From system of blood and bodies of a hemopoiesis: very seldom - a leukopenia, including an agranulocytosis, anemia (including hemolitic and aplastic), thrombocytopenia, a pancytopenia, a porphyria aggravation.
From an urinary system: very seldom - acute intersticial nephrite, renal failures, a giperkreatininemiya, increase in concentration of urea, a dysuria, an ischuria, an acute renal failure.
Allergic reactions: infrequently - skin rash, an itch, a small tortoiseshell; very seldom - a multiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), a photosensitization, an allergic pneumonitis, allergic nephrite, an eosinophilia, fever, a Quincke's disease, a bronchospasm; hypotonia, a hypertension, an acute anaphylaxis, an itch of external genitals at women.
Others: very seldom - an intestinal dysbiosis, superinfection, a stethalgia, hyper - or a hypoglycemia (at patients with a diabetes mellitus against the background of reception of anti-diabetic drugs), nasal bleeding, thirst, decrease in body weight, a vaginitis, allocations from a vagina, fatigue, an adynamy, the general weakness.

Interaction with other medicines:

At simultaneous use of an ofloksatsin with sukralfaty, the antiacid drugs and other drugs containing ions of metals (aluminum, magnesium, zinc or iron) absorption of an ofloksatsin decreases. Ofloxacin should be accepted in 2 hours prior to or in 2 hours after reception of these drugs.
Increase in efficiency of anticoagulating drugs of indirect action (coumarin derivatives), including warfarin is possible, at a concomitant use with ofloksatsiny. It is necessary to exercise control of coagulant system of blood.
At simultaneous use with non-steroidal anti-inflammatory drugs (NPVP), including with fenbufeny, and also with derivatives of a nitroimidazole and methylxanthines the risk of development of neurotoxic effects, including reduction of the threshold of convulsive activity increases.
At simultaneous use of an ofloksatsin and theophylline the clearance of theophylline decreases by 25% and theophylline T1/2 increases.
At simultaneous use with hypoglycemic drugs development both hypo - and a hyperglycemia is possible. At use with Glibenclamidum increases concentration of Glibenclamidum in a blood plasma and causes a condition of a hypoglycemia in this connection it is necessary to control concentration of glucose in a blood plasma.
At simultaneous use with cyclosporine increase in T1/2 and Cmax of cyclosporine in a blood plasma is noted.
Probenetsid, Cimetidinum, furosemide, a methotrexate at simultaneous use with ofloksatsiny reduce canalicular secretion of an ofloksatsin that leads to increase in concentration of an ofloksatsin in a blood plasma.
At simultaneous use with the drugs extending QT interval including the antiarrhytmic drugs IA and III of classes, tricyclic and tetracyclic antidepressants, neuroleptics, macroleads, antifungal drugs derivative of an imidazole, some antihistaminic drugs (астемизол, терфенадин, эбастин) lengthening of an interval of QT is possible.
At simultaneous use with drugs for not inhalation general anesthesia from group of barbiturates, hypotensive drugs perhaps sharp and considerable lowering of arterial pressure therefore in this case carrying out monitoring of indicators of cardiovascular system is required.
At simultaneous use with glucocorticosteroids (GKS) the risk of a rupture of sinews, especially at elderly patients increases.
At use with the medicines alkalizing urine (karboangidraza inhibitors, citrates, Natrii hydrocarbonas) the risk of a crystalluria and nephrotoxic effects increases.
Ofloxacin is not compatible to ethanol.

Contraindications:

Hypersensitivity to an ofloksatsin, other hinolona or other components of drug; age up to 18 years; pregnancy; breastfeeding period; deficit of a glyukozo-6-phosphate-dehydrogenase; epilepsy, including in the anamnesis; decrease in a convulsive threshold, including after a stroke; at a craniocereberal injury, an acute disorder of cerebral circulation, inflammatory diseases of the central nervous system; damages of sinews against the background of earlier carried out reception of ftorkhinolon; lactose intolerance, insufficiency of lactase, glyukozo-galaktozny malabsorption, peripheral neuropathy.

With care
Organic diseases of a brain, including atherosclerosis of vessels of a brain, disturbance of cerebral circulation (in the anamnesis); predisposition to convulsive reactions; gravis myasthenia; renal failure (clearance of creatinine (CC) less than 50 ml/min.); heavy abnormal liver functions; hepatic porphyria; diabetes mellitus; heart diseases, including chronic heart failure, a myocardial infarction, bradycardia, Bouveret's ventricular disease like "pirouette", a syndrome of inborn lengthening of an interval of QT; a concomitant use of the medicines extending QT interval including the antiarrhytmic drugs IA and III of the classes, tricyclic and tetracyclic antidepressants, neuroleptics, macroleads, antifungal drugs derivative of an imidazole, some antihistaminic drugs (астемизол, терфенадин, эбастин); concomitant use of drugs for not inhalation general anesthesia from group of barbiturates, hypotensive drugs; psychoses and other mental disturbances, including in the anamnesis; an electrolytic imbalance (for example, at a hypopotassemia, at a hypomagnesiemia); advanced age.

Overdose:

Symptoms: dizziness, confusion of consciousness, block, disorientation, spasms, drowsiness, vomiting, symptoms of irritation of mucous membranes.
Treatment: gastric lavage, artificial diuresis, symptomatic therapy; for stopping of neurologic disturbances (a convulsive syndrome) use diazepam.

Storage conditions:

To store at a temperature not above 25 °C in the place protected from light. To store in the place, unavailable to children. Period of validity 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 200 mg and 400 mg.
On 10 tablets in blisters from an aluminum foil / PVC / PVDH;
1, 2 or 5 blisters with the application instruction in a cardboard pack.