INSTRUCTION

for medical use of the preparation

OFLOXACIN

Composition:

Active substance: ofloxacin;

100 ml of the solution (1 container) contain ofloxacin 200 mg;

Auxiliary substances: sodium chloride, diluted hydrochloric acid, water for injections.

Medicinal form. Solution for infusions.

Pharmacotherapeutical group. Antibacterial agents for systemic use. Quinolone group. АТС code J01M A01.

Clinical characteristics.

Indications. Infectious and inflammatory diseases, caused by ofloxacin-sensitive causative agents:

•  acute and chronic infections of bronchopulmonary system;
•  acute and chronic infections of upper and lower departments of urinary tracts;
•  infections of skin and soft tissues;
•  infections of bones and joints;
•  sepsis.

Contraindications.

•  hypersensitivity to ofloxacin and other components of the preparation or other preparations of fluoroquinolone group;
•  epilepsy;
•  lesion of the central nervous system with decreased myoclonic threshold (after craniocerebral traumas, stroke, inflammatory processes of brain and brain tunics);
•  medical history of tendinitis;
•  glucose 6-phosphate dehydrogenase deficiency;
•  pregnancy;
•  lactation;
•  children’s age.

Ofloxacin should not be indicated to the patients with prolonged QT interval, to the patients with
noncompensated hypokaliemia, or to the patients taking antidysrhythmic medicinal preparations of class IА (quinidine, procaineamide hydrochloride) or class III (amiodarone, sotalol).

Way of introduction and doses. Used in adults. The preparation is introduced intravenously drop-by-drop. The introduction should be carried out in equal intervals. The dose of 200 mg should be introduced at least for 30 minutes.

Before the beginning of the introduction, skin allergy test should be carried out.

The dose of ofloxacin is indicated individually due to the susceptibility of microorganisms, type and severity of the infectious process.

Infections of bronchopulmonary system: 200 mg twice a day.

Infections of urinary tracts: 200 mg twice a day.

Sepsis: 200 mg twice a day.

At severe or complicated infection the preparation may be introduced in the dose of 400 mg twice a day.

Infections of bones and joints: 400 mg twice a day.

Infections of skin and soft tissues: 400 mg twice a day.

Dosing for patients with disturbed liver function: if creatinine clearance is 20 - 50 ml/min, the dose should be decreased to 100 - 200 mg every 24 hours. If creatinine clearance is <20 ml/min (including for the patients on hemodialysis or peritoneal dialysis), the dose should be 100 mg every 24 hours.

The duration of treatment depends on clinical course and in most cases is 7 - 10 days. After normalization of body temperature and improvement of general condition of the patient, the introduction of the preparation should be continued for 3 more days.

In cases of improvement of patient’s condition, it is recommended to continue the treatment with oral form of the preparation. The duration of treatment should not exceed 2 months.

Side effects.

From the side of the nervous system and psyche: agitation, dizziness, headache, sleep disturbance/insomnia, anxiety; psychotic reactions (with hallucinations), inquietudes, mental confusion, nightmares, depression, sleepiness, tremor, convulsions, disturbances of peripheral sensitivity (paresthesias, ataxia, impairment of taste, smell, sight); hearing impairments, such as tinnitus or hearing loss, photophobia, epileptic attacks, extrapyramidal disorders or other disorders of muscular coordination, increase of intracranial pressure.

From the side of cardiovascular system: possibility of short-term arterial hypotension, vasculitis.

From the side of the digestive system: nausea, vomiting, diarrhoea, dysbiosis, pseudomembranous colitis, hypoglycemia (in diabetic patients).

From the side of kidneys: seldom – increased level of urea and creatinine, in single cases – acute renal insufficiency, interstitial nephritis.

From the side of the liver: increased activity of hepatic enzymes (AST, ALT, LDH, GGT, alkaline phosphatase, bilirubin, cholestatic jaundice, hepatitis, possibly with severe clinical course.

From the side of the hematopoietic system: leucopenia, eosinophilia, thrombocytopenia, anemia, agranulocytosis, pancytopenia, suppression of medullary blood formation.

Musculoskeletal reactions: tendinitis, especially in elderly patients; arthralgias, myalgia.

Allergic and immune-associated reactions: skin rash, itch, photosensitization, face edema, Quincke's edema, and edema of the tongue and/or throat with possible asphyxia.

Local reactions: pain and reddening of the skin at the site of administration, in single cases - trombophlebitis.

Other: weakness, fever, vaginitis.

Overdose.

Symptoms: dizziness, disorientation, sleepiness, mental confusion, lethargy, convulsions, nausea, vomiting, erosion lesions of the mucous membranes.

The treatment is symptomatic.

Ofloxacin is excreted mainly by kidneys (75 - 80% of the administrated dose is excreted in the unchanged state with urine within 24 - 48 hours), its elimination may be accelerated by forced volumetric diuresis. Ofloxacin may be eliminated from the organism only in limited quantity by hemodialysis (on average 15 - 25%) or peritoneal dialysis (less than 2%).

Use during pregnancy and lactation.

The preparation is not used during pregnancy and lactation.

Children.

The preparation is not used in children.

Peculiarities of the use. If it is allowed by patient’s state, transfer to the treatment with appropriate doses of ofloxacin tablets is recommended.

In case of development of allergic reactions or evident side effects from the side of the CNS, the preparation should be discontinued immediatelly.

It is indicated with caution to the patients with CNS diseases (evident cerebral atherosclerosis, history of acute cerebrovascular insufficiency), in case if renal dysfunction.

In patients with acute hepatic insufficiency, the dose should not exceed 400 mg a day.

Patients should consume sufficient quantity of water in order to avoid crystalluria.

During treatment with ofloxacin, it is necessary to avoid solar irradiation.

It is necessary to correct the dose and time of introduction of the preparation in patients with renal insufficiency and elderly patients, taking into consideration prolonged excretion.

The ability to influence the reaction rate when driving or operating other mechanisms.

The use of the preparation may influence activity that requires high rate of mental and physical reactions, fast decision making (for example, when driving, operating machines and mechanisms, working at height, etc.).

Interaction with other medicinal preparations and other forms of interaction.

In case of concomitant use of ofloxacin with nonsteroidal antirheumatic drugs or medicinal preparations that decrease myoclonic threshold, the risk of convulsion development may increase.

Concomitant use of ofloxacin with procaineamide hydrochloride may lead to increased level of the latter – it is necessary to conduct thorough monitoring of procaineamide level in plasma and ECG in patients and, if necessary, to adjust its dosage.

In case of concomitant use of ofloxacin with antihypertensive agents or anesthetic barbiturates, in some case it is possible to observe sudden decrease of arterial pressure.

Concomitant use of ofloxacin with theophylline in single cases may lead to decreased excretion of the latter, which, however, is not clinically significant.

Concomitant use of ofloxacin in large doses with medicinal preparations, which are excreted by tubular secretion, may lead to increased plasma concentrations due to their decreased excretion.

In case of concomitant use with warfarin or its derivatives, it is necessary to control prothrombin time or carry out other appropriate clotting tests.

Taking into account possible hyperglycemia or hypoglycemia in case of ofloxacin administration in patients, who have been treated with antidiabetic agents, it is necessary to monitor the parameters of their compensation. During treatment with ofloxacin, false-positive results of opiate or porphyrin determination in the urine may be observed.

Pharmacological properties.

Pharmacodynamics. Ofloxacin is a synthetic antimicrobial agent of fluorinated quinolone of the broad spectrum of action.

In concentrations, identical to minimal inhibiting concentration (MIC) or higher, it has bactericidal action (by inhibiting DNA-gyrase, the enzyme necessary for replication and transcription of bacterial DNA).

The spectrum of antimicrobial action involves gram-negative and gram-positive bacteria, sensitive to ofloxacin: Enterobacteriaceae (Escherichia coli, species of Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, Yersinia),
Pseudomonas spp, including Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus ducreyi, Branhamella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Acinetobacter spр., Campylobacter spр, Gardnerella vaginalis, Helicobacter pylori, Pasteurella multocida, Vibrio spр, Brucella melitensis; staphylococci, including the strains, which produce penicillinase, and some strains, resistant to methicillin; it is also active against Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Ureaplasma urealyticum
(at limiting values of MIC), Mycobacterium tuberculosis, Mycobacterium leprae and some other microbacteria.

The sensitivity of streptococci of groups А, В and С is limited.

The majority of anaerobes, excluding Clostridium perfringens, are resistant.

Ofloxacin is inactive against Treponema pallidum.

Pharmacokinetics. Ofloxacin penetrates into tissues. It is also distributes well in body fluids, including cerebrospinal fluid. Rather high its concentrations are observed in bile. The volume of its distribution is 1.5 – 2.5 L/kg. Its binding to plasma proteins is 25%.

Ofloxacin in limited degree is transformed into desmethil-ofloxacin and ofloxacin
-N-oxide. Desmethil-ofloxacin has a weak antimicrobial activity.

Plasma half-life of ofloxacin is approximately 5 - 8 hours, in patients with renal insufficiency it is prolonged due to insufficiency degree up to 15 - 60 hours. Ofloxacin is excreted mainly by kidneys, tubular secretion and glomerular filtration. 75 - 80% of the excreted dose is excreted in unchanged state with urine within 24 - 48 hours, less than 5% is excreted as metabolites. 4 - 8% of the excreted dose is excreted with feces. The excretion of ofloxacin may be slowed in patients with severe hepatic lesion (for example, with cirrhosis). Irrespective of the dose, renal excretion of ofloxacin is 173 ml/min, total excretion – up to 214 ml/min. Only insignificant volume may be excreted with hemodialysis (15 - 25%), biological half-life against the background of hemodialysis is approximately 8 - 12 hours. In case of peritoneal dialysis biological half-disintegration is 22 hours.

Ofloxacin has post-antibiotic action.

Pharmaceutical characteristics.

Main physical and chemical properties: transparent, from colorless to yellowish color solution.

Incompatibility. Ofloxacin is incompatible with heparin and mannitol.

No other solutions and medicinal preparations should be added to the container with ofloxacin.

Shelf life. 2 years.

Storage conditions. Store in the original package in protected from light place at temperature below 25ºC.

Keep out of the reach of children.

Packing. 100 ml in a container, 1 container in a package.

Terms of dispensing. On prescription.

Name and location of the Manufacturer. Eurolife Healthcare Pvt. Ltd.

Khasra No. 520, Bhagwanpur, Poorkee, Haridwar, India; 69-А Mittal Chambers, Nariman Point, Mumbai-400021, India.

Name and location of the Applicant. Ananta Medicare Ltd.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, Great Britain.