INSTRUCTION

for medical use of the preparation

(GATILIN - 200)

(GATILIN - 400)

General characteristic: 

international and chemical names: gatifloxacine; 8-methoxyfluoroquinolone; 

main physical and chemical properties: white or almost white biconvex round (200 mg) film-coated tablets; white or almost white biconvex oblong (400 mg) film-coated tablets with a mark on one side;

composition: 1 tablet contains gatifloxacin 200 mg or 400 mg; 

auxiliary substances: microcrystalline cellulose, starch, calcium hydrophosphate, sodium methylparaben, sodium propylparaben, magnesium stearate, talc, sodium starch glycolate, polyethylenglyol-6000, hydroxipropylmethylcellulose, titanium dioxade, dibutyl phthalate.

Medicinal form. Film-coated tablets. 

Pharmacotherapeutical group. Antibacterial agent of quinolone group. АТС code J01M А16.  

Pharmacological properties. Gatifloxacine is and antimicrobial agent of fluoroquinolone group.

In vitro it is active against a broad spectrum of gram-negative and gram-positive microorganisms. Antibacterial action of gatifloxacine is a result of inhibition of DNA-gyrase and topoisomerase IV. DNA-gyrase is an essential enzyme, which takes part in replication, transcription and reparation of the bacterial DNA. Topoisomerase IV is an enzyme, which plays a key role in decomposition of chromosomal DNA during bacterial cell division.

Gatifloxacine is well absorbed from gastrointestinal tract after oral intake and can be used irrespectively of food intake. Absolute bioavailability of gatifloxacine is 96%. Maximal plasma concentration of gatifloxacine is usually observed in 1-2 hours after oral intake. Oral and intravenous ways of administration of gatifloxacine are usually considered to be interchangeable, as pharmacokinetics of gatifloxacine in 1 hour after intravenous introduction corresponds to its pharmacokinetics after oral intake in the same dose. Gatifloxacine pharmacokinetics is linear in the dose range between 200 and 800 mg used up to 14 days. Equilibrium state is achieved on Day 3 of oral (or intravenous) administration of gatifloxacine. Mean values of maximal and minimal plasma concentrations in equilibrium state when used in the dose of 400 mg once a day is approximately 4.2 and 0.4 g/ml in case of oral intake. Plasma proteins binding of gatifloxacine is approximately 20% and it is not concentration-dependent. Mean volume of gatifloxacine distribution in equilibrium state varies from 1.5 to 2 L/kg. Gatifloxacine is widely spread in many tissues and liquids of the organism. Rapid distribution of gatifloxacine in tissues leads to the achievement of its highest concentrations in most "target" tissues and organs in comparison with serum concentrations. Gatifloxacine is excreted mainly by kidneys in unchanged state (more than 70% within 48 hours after oral and intravenous administration), less than 1% is excreted with urine as ethylene diamine and methylene diamine metabolites; 5% is excreted with faeces. Mean half-life of gatifloxacine varies from 7 to 14 hours and does not depend on the dose or way or introduction. Renal clearance is not dose-dependent and is 124-161 ml/min. 

Indications. Chronic bronchitis in acute condition, acute sinusitis, community-acquired pneumonia, uncomplicated urinary tract infections (cystitis), complicated urinary tract infections, uncomplicated gonococcal urethritis and cervicitis.

Way of introduction and doses. Gatilin is taken once a day (at creatinine clearance > 40 ml/min) irrespectively from food intake, including milk and dietary supplements, which contain calcium. 

As gatifloxacin is excreted mainly with kidney excretion, the patients with creatinine clearance < 40 ml/min, including those on haemodialysis or long-term ambulatory peritoneal dialysis, require adjustment of dose regimen. The following changes of doses of the preparations in patients with renal insufficiency are recommended:

The regimen of single use of the preparation at the dose of 400 mg (for treatment of uncomplicated urinary tract infections and gonorrhoea) and 200 mg once a day for 3 days does not require dose adjustment in the patient with renal function disorder. There is no need to adjust the dose of Gatilin in the patients with moderate liver function disorder (Child-Pugh class C). There are no data on the patient with severe liver function disorder. 

Side effects. The most frequent are nausea, vaginitis, diarrhoea, headache, dizziness. Other clinically significant side effects are: allergic reactions, rigor, fever, backache, chest pain, tachycardia, abdominal pain, constipation, digestive disorders, candidiasis of tunica mucosa of the mouth, stomatitis, mouth ulcers, vomiting, peripheral edema, sleep disorders, insomnia, paresthesia, tremor, vasodilation, dizziness, dyspnoea, pharyngitis, rash, excessive sweating, visual impairment, taste impairment, ear noise, dysuria and hematuria, increased intracranial pressure, psychosis, anxiety, mental confusion, hallucinations, depression, nightmares, pain in tendon area, tendinitis, diarrhoea, pseudomembranous colitis. 

Similar to other quinolones, gatifloxacin can cause the development of arthropathy and/or chondropathy in the experiment.  

Contraindications.  Hypersensitivity to Gatilin or other quinolones. Pregnancy and lactation, children under 18 years old. 

Overdose. In case of acute overdose vomiting should be provoked or gastric lavage should be carried out. The treatment is symptomatic and supportive, as required. Adequate hydration should be provided. Haemodialysis and peritoneal dialysis in case of overdose are ineffective.

Precautions at use. Gatilin should not be indicated to patients with clinically significant bradycardia and myocardial ischemia. In the patients receiving quinolones there was observed increased intracranial pressure and psychoses. Quinolones can influence central nervous system, which can lead to the development of tremor, anxiety, headache, mental confusion, hallucinations, paranoia, depression, nightmares and insomnia. These reactions can develop after first dose intake. If such reactions are further observed, the preparation should be discontinued and corresponding treatment should be indicated. Similar to other quinolones, Gatilin should be used with caution in the patients with expressed cerebral atherosclerosis and epilepsy. Gatilin should be discontinued at the first signs of hypersensitivity. Gatilin should be discontinued, if the patient experiences pain in tendon area, tendinitis or ruptures of tendon. The patients should abstain from physical exercise until the diagnosis of tendinitis or ruptures of tendon is excluded with certainty. The development of pseudomembranous colitis is possible at use of nearly all antibacterial agents, including Gatifloxacin, varying from mild to life-threatening. That is why the probability of the development of pseudomembranous colitis in the patients, who developed diarrhoea during treatment with the preparation, should be taken into consideration. 

Interaction with other medicinal preparations. Gatilin should not be indicated to patients, receiving antiarrhythmic preparations of class IA (such as quinidine and procaineamide) or  class III (such as amiodarone and sotalol). As the studies on pharmacokinetic interaction between gatifloxacin and such preparations as cisapride, erythromycin, antipsychotic agents and tricyclic antidepressants, have not been conducted, Gatilin should be used with caution in such combinations. Gatilin should be taken at least 4 h before administration of iron sulphate, compounds of zinc, magnesium or iron (including those in the composition of multivitamin preparations), antacids, containing aluminium or magnesium, or didanosine as buffer tablets, or solution of the powder for oral suspension preparation. There is no need to adjust the dose of Gatilin at concomitant use of calcium carbonate, cimetidine, theophylline, gliburide or mindazol. Concomitant use of gatifloxacin and digoxin did not cause significant changes of pharmacokinetics of gatifloxacin; but in some patients there is observed increases digoxin concentration. That is why the patients receiving digoxin in combination with gatifloxacin, should be monitored by the doctor as for timely revealing of toxicity signs. Systemic exposition of gatifloxacin increases significantly after single use with probenecid. As there has been observed increased action of warfarin and its derivatives under the influence of some quinolones, at indication of such combination, prothrombin time and other indexes of coagulation blood system should be controlled. 

Storage conditions and shelf-life. Keep out of the reach of children in a dry protected from light place at temperature below 25єC. Shelf-life is 2 years.

Terms of dispensing. On prescription.   

Packing. 10 tablets in a blister, 1 blister in a package.  

Name and Address of the Manufacturer. Ananta Medicare Ltd.

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