Ofloxacin

General characteristics. Structure:

Active agent: ofloxacin — 200 mg.

Excipients (kernel): potato starch — 2,100 mg, cellulose microcrystallic — 93,850 mg, magnesium stearate — 3,000 mg, povidone (polyvinylpirrolidone) — 7,410 mg, croscarmellose sodium — 1,640 mg.

Excipients (cover): a gipromelloza — 3,684 mg, a macrogoal — 1,228 mg, titanium dioxide — 2,088 mg.

Pharmacological properties:

Antimicrobic broad-spectrum agent from group of ftorkhinolon, affects bacterial DNK-gidrazu enzyme, the providing superspiralling and, thus, stability of DNA of bacteria (destabilization of chains of DNA leads to their death). Renders bactericidal effect. It is highly active concerning the majority of gram-negative and some gram-positive microorganisms: Ayegogtta-nas hydrophila, Branhamella catarrhalis, Brucella spp., Clostridium perfringens, Escherichia coll, Salmonella spp. Enterobacter spp., Serratia spp., Citrobacter spp., Yersinia spp. Providencia spp. Haemophilus influenzae and parainfluenzae. Haemophilus.ducreyi, Plesiomonas, Legionella, Shigella spp., Proteus spp., including Proteus mirabilis, Proteus vulgaris (indol +, indol-), Moraxella rnorganii, Klebsiella spp. (including Klebsiella pneumonia), Helicobacter pylori, Mycoplasma spp., Vibrio spp. Gardncrella vaginalis. Neisseria gonorrhoeae. Neisseria meningitidis, Chlamydia trachomatis. Staphylococcus aureus methi-S, Staphylococcus coagulase negative. Are moderately sensitive to Acinetobacter spp ofloksatsin., Ureaplasma urealyticum, Bacteroides fragilis, Mycobacterium tuberculosis, Mycobacterium fortuitum, Chlamidia psittaci, anaerobic gram-positive cocci. Enterococcus faecalis, Streptococcus pneumoniae. Pseudomonas spp. Streptococcus spp. (especially beta and hemolitic).
To an ofloksatsin Acinetobacter braumanmii,  Clostridium difficile are insensitive. Enterococci, Listeria onocytogenes, Staphylococci methi-R, Nocardia spp.
Ofloxacin is inactive concerning Treponema pallidum.

Pharmacokinetics. Absorption after intake bystry and full (95%). Bioavailability — over 96%, communication with proteins of plasma — 25%. Time of achievement of the maximum concentration (Tstakh) at oral administration is 1-2 h. The maximum concentration (Experience) after reception in a dose of 100, 200, 300 and 600 mg makes 1, 3, 4 and 6, 9 mg/l respectively and depends on a dose: after a single dose of 200 and 400 mg it makes 2.5 and 5 mkg/ml respectively. Food can slow down absorption, but has no significant effect on bioavailability. Distribution volume — 100 l. Distribution: cells (leukocytes, alveolar macrophages), skin, soft tissues, bones, abdominal organs and small pelvis, respiratory system, urine, saliva, bile, prostate secret; well gets through a blood-brain barrier, a placental barrier, cosecretes with maternal milk. Gets into cerebrospinal fluid (14-60%).
It is metabolized in a liver (about 5%) with formation of N-Oksid of an ofloksatsin and dimetilofloksatsin. An elimination half-life (T1/2) — 4.5-7 h (irrespective of a dose). It is removed by kidneys — 75-90% (in not changed look), about 4% — with bile. Extrarenal clearance — less than 20%.
After single use in a dose of 200 mg in urine it is found during 20-24 h. At a renal/liver failure removal can be slowed down. Does not kumulirut. At a hemodialysis 10-30% of drug are removed.

Indications to use:

Treatment of the infectious and inflammatory diseases caused by microorganisms, sensitive to an ofloksatsin:
— respiratory infections (except for cases of a pneumococcal infection):
— infections of an ear, a throat, a nose (except for cases of acute tonsillitis);
— infections of an abdominal cavity and biliary tract;
— infections of kidneys, urinary tract, prostate, urethra (including gonococcal nature);
— infections of bodies of a small pelvis;
— infections of bones and joints;
— infections of skin and soft tissues;
— prevention of infections at patients with disturbance of the immune status (including at a neutropenia).

Route of administration and doses:

Inside.
The dose of an ofloksatsin and duration of treatment depend on weight and a type of an infection, the general condition of the patient and function of kidneys.
Average daily dose for adults — from 200 mg to 600 mg. Treatment duration — 7-10 days. It is possible to appoint a dose to 400 mg/days in 1 reception, predpochtiktelno in the morning. Doses over 400 mg/days should be divided into 2 receptions with equal periods. A pill should be taken entirely, washing down them with water both to, and during food. It is necessary to avoid a concomitant use together with antacids.
At heavy infections or at treatment of patients with an excess weight the daily dose can be increased to 800 mg At uncomplicated infections of lower parts of urinary tract drug appoint in a dose 200 mg/days within 3-5 days. At gonorrhea appoint 400 mg once. At patients with renal failures the dose has to be reduced depending on clearance of creatinine:

Clearance of creatinine	Single dose	Interval between doses
50-20 ml/min.	100-200 mg	24 hours
less than 20 ml/min. or гемо­диализ	100 mg	24 hours
hemodialysis less than 20 ml/min. or hemodialysis	200 mg	48 hours

At patients with a liver failure it is not recommended to exceed the maximum daily dose of 400 mg.

Features of use:

Because ofloxacin is removed generally through kidneys, at patients with a renal failure dose adjustment of an ofloksatsin is necessary. Due to the risk of emergence of a photosensitization, it is necessary to avoid impact of a sunlight and ultraviolet rays. Emergence of diarrhea, especially in a severe form, persistent and/or with blood impurity, in time or after treatment ofloksatsiny can be display of pseudomembranous colitis. At suspicion on development of pseudomembranous colitis treatment ofloksatsiny has to be immediately stopped, and the corresponding specific antibacterial therapy has to be appointed urgently. In this clinical situation the drugs suppressing an intestines peristaltics are contraindicated.
As well as other hinolona, ofloxacin it has to be appointed with extra care the patient predisposed to development of epileptic seizures (the patients with injury of the central nervous system to the anamnesis accepting фенбуфен and the similar non-steroidal anti-inflammatory drugs or drugs lowering a threshold of convulsive activity, for example, theophylline).
The tendinitis arising very seldom can sometimes lead to a rupture of sinews, is preferential an Achilles tendon, especially at elderly patients. In case of signs of a tendinitis (a sinew inflammation), it is recommended to stop immediately treatment, to make an immobilization of an Achilles tendon and to provide consultation of the orthopedist. A certain care at reception of ftorkhinolon is necessary, including ofloxacin, patients with the known risk factors have lengthenings of an interval FROM, such as:
— advanced age;
— not adjusted imbalance of electrolytes (for example, a hypopotassemia, a hypomagnesiemia);
— inborn lengthening of an interval of QT;
— diseases of cardiovascular system (heart failure, myocardial infarction, bradycardia);
— a concomitant use of the drugs extending QT interval (IA and the III classes of antiarrhytmic drugs, tricyclic antidepressants, macroleads).
Ofloxacin can lead to deterioration in a current of a myasthenia. Increase of attacks of a porphyria is possible. During treatment ofloksatsiny emergence of false positive results when determining opiates and porphyrines in urine is possible. Ofloxacin interferes with Mycobacterium tuberculosis allocation, resulting in false-negative results at bacteriological diagnosis of tuberculosis. Also during treatment it is not recommended to use ethanol. Ofloxacin is not choice drug at the pneumonia caused by pneumococci. It is not shown at treatment of acute tonsillitis. Driving or other mechanisms during treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

- From the alimentary system: gastralgia, loss of appetite, nausea, vomiting, diarrhea, meteorism, abdominal pain, increase in activity of "hepatic" transaminases, hyperbilirubinemia, cholestatic jaundice, pseudomembranous coloenteritis.
- From a nervous system: headache, dizziness, uncertainty of movements, tremor, spasms, numbness and paresthesias of extremities, intensive dreams, "dreadful" dreams, psychotic reactions, uneasiness, condition of excitement, phobia, depression, confusion of consciousness, hallucination, increase in intracranial pressure.
- From a musculoskeletal system: the tendinitis, mialgiya, arthralgias, tendosinovit, a rupture of a sinew.
- From sense bodys: disturbance of color perception, diplopia, disturbances of taste, sense of smell, hearing and balance.
- From cardiovascular system: tachycardia, lowering of arterial pressure (ABP).
- Allergic reactions: skin rash, itch, small tortoiseshell, allergic pneumonitis, allergic nephrite, eosinophilia, fever, Quincke's disease, bronchospasm; multiformny exudative erythema (including Stephens-Johnson's syndrome) and toxic epidermal necrolysis (Lyell's disease), photosensitization, vasculitis, acute anaphylaxis.
- From integuments: dot hemorrhages (petechias), violent hemorrhagic dermatitis, papular rash with a crust, testimonial of defeat of vessels (vasculitis).
- From bodies of a hemopoiesis: leukopenia, agranulocytosis, anemia, thrombocytopenia, pancytopenia, hemolitic and aplastic anemia.
- From an urinary system: acute intersticial nephrite, renal failure, giperkreatininemiya, increase in concentration of urea. Other: an intestinal dysbiosis, superinfection, a hypoglycemia (at patients with a diabetes mellitus), a vaginitis.

Interaction with other medicines:

The antacids containing aluminum hydroxide (including сукральфат) and magnesium hydroxide, aluminum phosphate, zinc, iron reduce absorption of an ofloksatsin. At reception of antacids and an ofloksatsina between their reception it is necessary to observe approximately two-hour interval.
At simultaneous use of antagonists of vitamin K control of coagulant system of blood is necessary. Ofloxacin can slightly increase serumal concentration of Glibenclamidum at simultaneous use.
In case of use of high doses of an ofloksatsin and other medicines which are removed by means of renal tubular secretion such as пробенецид, Cimetidinum, furosemide or a methotrexate, increase in concentration of an ofloksatsin in blood serum is possible.
Noticeable reduction of the threshold of convulsive activity can be observed at purpose of ftorkhinolon in combination with theophylline, fenbufeny or other non-steroidal anti-inflammatory drugs, and also other drugs lowering a threshold of convulsive activity. At appointment together with the non-steroidal anti-inflammatory drugs derivative of a nitroimidazole and methylxanthines the risk of development of neurotoxic effects increases.
At co-administration with glucocorticosteroids the risk of a rupture of sinews, especially at elderly people increases.
At joint appointment with drugs as QT extending an interval (IA and the III classes of antiarrhytmic drugs, tricyclic antidepressants, macroleads) the risk of lengthening QT interval increases.
At appointment with the medicines alkalizing urine (karboangidraza inhibitors, citrates, Natrii hydrocarbonas) the risk of a crystalluria and nephrotoxic effects increases.

Contraindications:

— hypersensitivity to an ofloksatsin, other hinolona or components of drug;
— epilepsy;
— damage of the central nervous system with the lowered convulsive threshold (after a craniocereberal injury, a stroke, inflammatory processes in the central nervous system (CNS);
— damage of sinews at earlier carried out treatment of a hinolonama:
— deficit glyukozo-6-fosfatdegidrogenazy;
— age up to 18 years;
— pregnancy and period of a lactation.

With CARE: at patients with atherosclerosis of vessels of a brain, disturbance of cerebral circulation (in the anamnesis), a chronic renal failure, organic lesions of TsNS, with lengthening of an interval of QT.

Overdose:

Symptoms: dizziness, confusion of consciousness, block, disorientation, drowsiness, vomiting. In case of overdose it is recommended to carry out a gastric lavage and symptomatic therapy. The specific antidote does not exist.

Storage conditions:

List B. To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 200 mg. On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 10, 20, 30 tablets in a container polymeric for medicines.
One container or 1, 2, 3 blister strip packagings together with the application instruction place in a pack from a cardboard.