COMPOSITION:

active substance:

gatifloxacin;

1 tablet contains gatifloxacin sesquihydrate equivalent to gatifloxacin 400 mg;

other ingredients:

Corn starch, povidone K-30, microcrystalline cellulose, magnesium stearate, colloidal anhydrous silica, croscarmellose sodium,

Opadry 03В52014 yellow: hydroxypropylmethicellulose, titanium dioxide (E171), macrogol, quinoline yellow (E104), iron oxide yellow (Е 172).

INDICATIONS:

Treatment of infectious and inflammatory processes caused by microorganisms which are sensitive to the drug, such as:

– acute sinusitis;

– respiratory infections (acute bronchitis, exacerbation of acute bronchitis, community acquired pneumonia);

– complicated infections of kidneys and urinary system (including acute pyelonephritis, cystitis; urethritis, chronicinfectionsof urinary system);

– gonorrhea (uncomplicated urethritis, cervicitis).

DOSAGE:

The drug is taken regardless ofmeals, usually 1 time per day.

Acute bronchitis, exacerbation of chronic bronchitis:

400 mg1 time per day; duration of treatment – 5 – 7 days.

Acute sinusitis:

400 mg1 time per day; duration of treatment – 10 days.

Community acquired pneumonia:

400 mg1 time per day or 200 mg2 times per day; duration of treatment – 7 – 14 days.

Uncomplicatedinfectionsof urinary tract (cystitis):

400 mg1 time per day or 200 mg 2 times per day; duration of treatment – 3 days.

Complicatedinfectionsof urinary tract:

400 mg 1 time per day or 200 mg 2 times per day; duration of treatment – 7 – 10 days.

Acute pyelonephritis:

400 mg 1 time per day; duration of treatment – 7 – 10 days.

Uncomplicated urethral gonorrhea in men, cervical gonorrhea in women:

single dose of 400 mg1 time per day.

As gatifloxacin is excreted primarily by renal excretion, patients with creatinine clearance < 40 mL/min, except for patients on hemodialysis or long-term ambulatory peritoneal dialysis, need adjustment of dosage regimen.

The following changes in dosage regimen are recommended for patients with renal insufficiency:

The scheme with a single dose of the drug of 400 mg (for treatment of uncomplicated infections of urinary tract and gonorrhea) and 200 mg 1 time per dayfor 3 days does not require dosage adjustment in patients with renal dysfunction.

ADVERSE REACTIONS:

The most common adverse effects of gatifloxacin are vertigo, vomiting, diarrhea, vaginitis, abdominal pain, headache. Also possible:

Immune system:

chills, fever, anaphylactoid reactions, anaphylaxis, vasculitis, eczema, angioedema;

skin:skin rush, urticaria, erythema,itching, photosensibilization, phototoxicity, allergic dermatitis, sweating, dry skin, Stevens-Johnson syndrome;

Nervous system:

agitation, excitement, disturbance and loss of consciousness, depression, nervousness, restlessness, anxiety, nightmares paranoia, sleep disorder, insomnia, somnolence, paresthesia, impaired sense of taste, tremors, convulsions, blurred vision, tinnitus, ototoxicity;

cardiovascular system:

palpitation, hypertension or hypotension, peripheral edema, vasodilation, QT prolongation on the ECG, syncope, torsades de pointes;

Digestive system:

Anorexia, constipation, dyspepsia, flatulence, glossitis, gastritis, oral candidiasis, stomatitis, mouth ulcers, heartburn, appetite disturbance, vomiting, nausea, thirst, dry mouth, pancreatitis;

Musculoskeletal system and connective tissue:

arthropathy, arthralgia, myalgia, muscle spasms, impaired articular cartilage, tendonitis, tendovaginitis, tendon rupture;

Hepatobiliary system:

elevated liver enzymes, cholestatic jaundice, hepatitis, pain in right hypochondrium;

Endocrine system:fluctuation in blood glucose – hypoglycemia (including hypoglycemic coma), hyperglycemia (includinghyperosmolar nonketonemic hyperglycemia);

Urinary system:renal dysfunction, includingacute renal failure, crystalluria, transient nephritis,dysuria and hematuria are rare;

Respiratory system:dyspnea, pharyngitis;

Laboratory abnormalities:neutropenia, increased levels of ALT, AST, alkaline phosphatase, bilirubin, amylase, electrolyte disorders, increased prothrombin time, thrombocytopenia;

common disorders: asthenia (weakness), back pain, chest pain.

Other adverse reactionsmay occur when usinggatifloxacinin mono- or combined therapy:

aphronia, impaired tolerance to alcohol, arthritis, asthma (bronchospasm), ataxia, bone pain, bradycardia, cheilitis, colitis, cyanosis, depersonalization, dysphagia, ear pain,ecchymosis, epistaxis, euphoria, eye pain, photosensitivity of eyes, gastrointestinal hemorrhage, generalized edema, gingivitis, hostility, hallucinations, uterine bleeding, hematuria, hyperesthesia, hyperventilation, hypoglycemia, lymphadenopathy, maculopapular rash, metrorrhagia, headache, lips swelling, myalgia, myasthenia, neck pain, panic attacks, paranoia, paraosmiya, photophobia, pseudomembranous colitis, psychosis, ptosis, rectal hemorrhage, stress, substernal pain, vesicle-bullous rash.

Drug interactions:

Administration ofgatifloxacin1 hour after cimetidine (1 time per day,oral dose of 200 mg) has no effect on gatifloxacin pharmacokinetics. These results suggest that, absorption gatifloxacinis not affected histamine H2-receptor antagonists, such as cimetidine and famotidine.

Concomitant administration ofgatifloxacinantacids reduces its bioavailability.

The use ofgatifloxacindoes not affect systemic clearance of intravenous midazolam. Daily intravenous dose of midazolam of 0.0145 mg/kgdoes not affectgatifloxacin pharmacokinetics. These results may be considered in case of insufficient efficacy of gatifloxacinduring studies with CYP3A4 isoenzyme in humans.

Concomitant use of gatifloxacintheophylline had no effect on pharmacokinetics of any of these drugs.

Concomitant use of gatifloxacin and warfarinhad no effect on pharmacokinetics of any of these drugs; there were no changes in prothrombin time.

Concomitant use of gatifloxacinwith hypoglycemic oral drugs can lead to fluctuations in blood glucose (hypoglycemia or hyperglycemia may occur);therefore it is necessary to monitor blood glucose values during treatment with gatifloxacin. In case of health-threatening deviations of blood glucose level, gatifloxacin should be discontinued.

The risk of development of ventricular arrhythmias when usinggatifloxacinincreases and poses a real danger for elderly patients, especially for females,in the presence of heart diseases, concomitant administration of drugs that prolong the QTc interval (cisapride, erythromycin, antipsychotics and tricyclic antidepressants) or slow the heart rate (Class 1A (e.g. Quinidine, procainamide ), or Class 111 (e.g. amiodarone, sotalol) antiarrhythmic agents, which cause kaliopenia), as well as concomitant administration of drugs that have competing metabolic pathways and alter the concentration of each other.

Concomitant administration of gatifloxacinand digoxin did not produce significant alteration of the pharmacokinetics ofgatifloxacin. Patients taking digoxin should, therefore, be monitored for signs and/or symptoms of toxicity.In patients who display signs and/or symptoms of digoxin intoxication, serum digoxin concentrations should be determined, and digoxin dosage should be adjusted as appropriate.

Systemic exposure to gatifloxacin is increased following the concomitant administration of gatifloxacinand probenecid.

Pre-clinical and clinical studies have revealed thatconcomitant administration offluoroquinoloneswith nonsteroidal anti-inflammatory drugs may increase the risk ofcentral nervous system disorders and convulsions.

It is not recommended Levofloxacin concomitant usage with alcohol.

Pregnancy and lactation:

The drug is contraindicated during pregnancy.

During the period of drug therapy, breast-feeding should be stopped.

Children:

The drug is not prescribed to children and adolescents under 18.

Overdose:

abdominal pain, convulsive seizures, tremor, psychosis, impaired vision and hearing, prolongation of QT interval on an electrocardiogram.

Treatment:

gastric lavage. The patient should stay under medical supervision andreceive symptomatic treatment. Rehydration therapy should be applied according to the patient’s condition.Gatifloxacinis not effectively eliminated by hemodialysis (about 14% during 4 h) or by forced hemodialysis (about 11% in 8 days).

Ability to influence reaction velocity while driving or operating any other mechanisms.

The drug should be used with caution when driving and operating complex mechanisms (may cause dizziness).

CONTRAINDICATIONS:

Hypersensitivity togatifloxacinand other fluoroquinolonesin the anamnesisor other components of the drug.

Diabetes mellitus, diseases of the central nervous system (epilepsy, low seizure threshold).

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics.Gatifloxacinis active against a wide range of gram-positive and gram-negativemicroorganisms;therefore, it is indicated for treatment of diseases, caused by the following pathogens:

– gram-positivemicroorganisms:

susceptible – Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenesandrelativelysusceptible – Streptococcus milieri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus cohnii, Staphylococcus epidermidis (includingmethicillin-resistant strains), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae;

– gram-negativemicroorganisms:

susceptible – Haemophillus influenzae (includingstrains that produce β-lactamase), Haemophilias раrаinfluenzae: Klebsiella pneumoniae, Moraxella catarrhalis (includingstrains that produce β-lactamase), Escherichia coli, Enterobacter cloacae, Neisseria gonorrhoеae(includingstrains that produce β-lactamase) andrelativelysusceptible – Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mіrabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii

– relativelysusceptibleanaerobes:

Bacteroides distasonis, Bacteroides eggerthiі, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella spp., Propionibacterium spp., Ctostridium perfringens, Clostridium ramosum;

– susceptibleatypicalpathogens:

C.pneumoniae, C. trachomatis, M.pneumoniae, L. Pneumophilia, Ureaplasma;

– relativelysusceptibleatypicalforms:

Legionella pneumophila, Caxiella burnettii.

Suchpathogens asbacillus Kochii andH. рylori are susceptible to gatifloxacin.

Antibacterial effect ofgatifloxacinis due to suppression of DNA-gyraseand topoisomerase IV. DNA-gyrase is an important enzyme participating in DNA replication of pathogens.

Topoisomerase IV is an enzyme that plays a certain role in the distribution of chromosomes during bacterial cell division.

Gatifloxacinis effective againstbacteria resistant to β-lactam macrolide antibiotics.

Pharmacokinetics. The absolute bioavailability of gatifloxacin is 96%. Peak plasma concentrations of gatifloxacin occur 1-2 hours after oral dosing. Serum protein binding of gatifloxacin is approximately 20%.

Gatifloxacin is widely distributed into many body tissues and fluids. High concentrations are formed inlung tissue, bronchial mucosa, paranasal sinuses, alveolar macrophages, middle ear tissues, skin tissues, prostate tissues and prostatic fluid, saliva, bile, seminal fluid, vagina, womb, endometrium, myometrium, oviduct and ovary.

Gatifloxacin undergoes limited biotransformation in humans with <1% of the dose excreted in the urine.>

Is excreted by kidneys. The mean elimination half-life of gatifloxacin ranges from 7-14 hours and is independent dose and administration regimen.

In animal studies gatifloxacin freely crossed the placenta and appeared in breast milk.

Differences in the pharmacokinetics of gatifloxacin were noted in female subjects. Elderly females had a 21% increase in maximum plasma concentration,a 32% increase in area under the curve “concentration-time” (AUC) (0-) and slower excretion compared with younger females.

Pediatrics.Pharmacokinetics ofgatifloxacinin children has not beenestablished.

Renal failure.In patients with renal failuregatifloxacinclearance is decreased,the systemic effect is more pronounced.

PHARMACEUTICAL CHARACTERISTICS:

General physical-chemical properties:

round biconvex tablets with yellow coating.

Shelf-life:

3 years.

Storage conditions:

Store at a temperature not exceeding 25 °С in a dry place protected from sunlight out of reach of children.

Package:

10 tablets in a blister, 1 blister in a carton, 10 cartons in a box.

Conditions of supply:

By prescription.