INSTRUCTION

for medical use of medicinal product

 

 GATILIN

 

Composition:

active substance: gatifloxacin;

100 ml of solution contains gatifloxacin sesquihydrate equivalent to gatifloxacin 200 mg or 400 mg;

Excipients:

Gatilin (200 mg/100 ml): glucose anhydrous, hydrochloric acid concentrated, water for injection;

Gatilin (400 mg/100 ml): glucose anhydrous, hydrochloric acid concentrated, sodium hydroxide, water for injection.

 

Pharmaceutical form. Solution for infusion.

Basic physical and chemical properties: a clear colourless to pale yellow solution.

 

Pharmacotherapeutic group. Antibacterial agents of quinolone group. Fluoroquinolones

ATC code: J01M A16.

 

Pharmacological properties.

Pharmacodynamics.

Gatifloxacin is a 8-methoxyfluoroquinolone, which has antibacterial activity against a wide range of gram-negative and gram-positive aerobic microorganisms, anaerobes and intracellular pathogens. The antibacterial effect of gatifloxacin is provided by suppressing DNA gyrase and topoisomerase IV. DNA gyrase is an important enzyme involved in the reduplication of DNA pathogens. Topoisomerase IV is an enzyme that plays a leading role in the replication of DNA chromosomes when bacterial cell reduplicated.

Gatifloxacin susceptible microorganisms are as follows:

Gram-positive microorganisms ‒ Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus milieri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus cohnii, Staphylococcus epidermidis (including methicillin-resistant strains), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae;

Gram-negative microorganisms Haemophillus influenzae (including strains producing β-lactamase), Haemophilias раrаinfluenzae_, Klebsiella pneumoniae, Moraxella catarrhalis (including strains producing β-lactamase), Escherichia coli, Enterobacter cloacae, Neisseria gonorrhoеae (including strains producing β-lactamase); Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mіrabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii;

Anaerobes ‒ 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;

Atypical pathogens Сhlamydia pneumoniae, Сhlamydia trachomatis, Mycoplasma pneumoniae, Mycoplasma hominis, Legionella pneumophila, Ureaplasma; Caxiella burnettii.

Tuberculosis mycobacteria such as Helicobacter Pylori are susceptible to gatifloxacin.

Gatifloxacin is effective against bacteria resistant to β-lactam and macrolide antibiotics.

Pharmacokinetics.

Absolute bioavailability of gatifloxacin in patients is 96%.

Oral and intravenous methods of administration are interchangeable because the pharmacokinetic parameters after intravenous administration for 1 hour are similar to the pharmacokinetic parameters after oral administration.

Binding to plasma proteins is about 20% and does not depend on the preparation concentrations in the blood.

Gatifloxacin penetrates into most tissues of the body and distributes in biological fluids rapidly. High concentrations are formed in the pulmonary tissue, mucous bronchi, adnexal cavity of the nose, alveolar macrophages, middle ear tissues, skin tissues, tissues and secretions of prostate, saliva, bile, vaginal fluid, vagina, uterus, endo- and myometrium, fallopian tubes and ovaries.

Gatifloxacin is mainly excreted by the kidneys in the unchanged state. More than 70% of the administered dose of the preparation is excreted unchanged in the urine within 48 hours after intravenous administration and 5% – in feces.

No information is available regarding pharmacokinetics alterations of gatifloxacin in patients with severe hepatic insufficiency.

Pharmacokinetics in patients under 18 years of age have not been studied.

 

Clinical particulars.

Indications.

Treatment of infectious and inflammatory diseases caused by gatifloxacin susceptible microorganisms:

• 1) respiratory tract infections (including exacerbation of chronic bronchitis (only if other antibacterial drugs commonly prescribed for the treatment of these infections are found to be ineffective or inappropriate), acute sinusitis (only if other antibacterial drugs commonly prescribed for the treatment of these infections are found to be ineffective or inappropriate), community-acquired pneumonia);
• 2) kidney and urinary system infections: cystitis, pyelonephritis (with and without complications);
• 3) sexually transmitted diseases: urethral gonorrhea without complications, rectal gonorrhea without complications in women.

Official guidelines for the proper use of antibacterial drugs should be considered.

 

Contraindications.

• 1) Hypersensitivity to gatifloxacin and other fluoroquinolones in anamnesis or other components of the medicinal product.
• 2) Diabetes mellitus.

 

Interaction with other medicinal products and other forms of interaction.

The use of gatifloxacin does not affect the systemic clearance of intravenously administered midazolam. A single intravenous administration of midazolam at the dose of 0.0145 mg/kg does not affect the pharmacokinetics of gatifloxacin. These results do not contradict the fact that during in vitro studies on human isozymes, CYP3A4, gatifloxacin did not show any effect.

The co-administration of gatifloxacin and theophylline did not affect the pharmacokinetics of any of these medicinal products.

The co-administration of gatifloxacin and glyburide (at steady state – once a day) in patients with diabetes mellitus type 2 did not affect the pharmacokinetics and pharmacodynamics of any of these medicinal products. Fasting glucose concentrations have not been changed.

No interaction was determined when above mentioned medicinal products were co-administrated with gatifloxacin. In addition, not every case requires dosage adjustments.

The co-administration of gatifloxacin and digoxin did not gatifloxacin pharmacokinetics significantly. Patients taking digoxin should be monitored for manifestations and/or symptoms of intoxication development. In patients with manifestations and/or symptoms of digoxin intoxication, serum digoxin concentrations should be checked and digoxin doses should be adjusted.

Systemic excretion of gatifloxacin is increased significantly when gatifloxacin and probenecid used concomitantly.

No significant changes in coagulation time were registered when gatifloxacin administrated concomitantly to patients treated with warfarin. However, considering the fact that some quinolones increase the effect of warfarin or its derivatives, the prothrombin time or other appropriate coagulation tests should be strictly controlled if antibacterial quinolone is to be administered in combination with warfarin or derivatives of gatifloxacin.

During preclinical and clinical studies, it has been found that when nonsteroidal anti-inflammatory drugs and quinolones are administrated concomitantly, the quinolones may increase the risk of seizures and central nervous system disorders.

Tricyclic antidepressants, derivatives of phenothiazine, erythromycin, and cisapride increase the risk of heart rhythm disorders.

 

Peculiarities for use.

The medicinal product should not be used in patients with a history of serious adverse reactions to quinolones or fluoroquinolones. Treatment of such patients with levofloxacin should be initiated only in the absence of alternative treatment options and after a thorough benefit/risk assessment.

Long-term, disabling and potentially irreversible adverse reactions.

In very rare cases, patients treated with quinolones and fluoroquinolones, regardless of age and existing risk factors, have experienced prolonged (lasting months or years), disabling and potentially irreversible serious adverse reactions affecting various, and sometimes multiple, body systems (including the musculoskeletal and nervous system, mental health or sensory organs). Treatment should be discontinued immediately at the first sign of any serious adverse reaction, and medical advice should be sought.

Gatifloxacin may increase the QT interval prolongation on ECG in some patients.

Due to insufficient clinical experience, gatifloxacin should not be used for patients with prolonged QT intervals, for hypercalcemia patients and for patients receiving class IA drugs (quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmics.

Pharmacokinetic studies of gatifloxacin and prolonged QT interval drugs, such as cisapride, erythromycin, antipsychotics and tricyclic antidepressants, have not been performed. Gatifloxacin should be used with caution in combination with such drugs.

Caution should be exercised when Gatilin is applied to patients with heart disease, such as bradycardia and acute myocardial ischemia.

The probability of prolongation of the QT interval may be increased due to increased concentration of gatifloxacin. Considering this fact the recommended dose should not be exceeded. Prolongation of the QT interval may increase the risk of ventricular arrhythmias.

Aortic aneurysm and dissection.

Epidemiologic studies indicate an increased risk of aortic aneurysm and aortic dissection after taking fluoroquinolones, especially in elderly patients.

Thus, fluoroquinolones should be used only after a thorough benefit/risk assessment and after considering other therapeutic options for patients with a positive family history of aneurysm and for patients diagnosed with aortic aneurysm and/or aortic dissection, as well as in the presence of risk factors or conditions that cause aortic aneurysm and aortic dissection (e.g., Marfan syndrome, Ehlers-Danlos vascular syndrome, Takayasu arteritis, giant cell arteritis, Behçet's disease, hypertension, known atherosclerosis).

In the event of sudden abdominal pain, chest pain, or back pain, patients should be advised to seek immediate medical attention in an emergency department.

In cases of hypersensitivity to Gatilin and the development of anaphylactic shock, some serious and fatal cases were observed in patients treated with quinolone.

Gatifloxacin should not be used in the first signs of hypersensitivity – skin rashes and other allergic reactions.

Caution should be exercised when gatifloxacin is administrated to patients with renal insufficiency. Careful clinical examination and appropriate laboratory tests should be performed before and during treatment. If necessary, the dose of gatifloxacin should be lowered. Dose adjustment (dose reduction) should be performed in patients with impaired renal function (creatinine clearance < 40 ml/min) to avoid accumulation of gatifloxacin due to reduced clearance.

Blood sugar concentration control is necessary when using Gatilin.

Due to disturbance of blood glucose levels caused by Gatilin application, including symptoms of hyper- and hypoglycemia, especially in patients with diabetes mellitus who receive concomitant hypoglycemic or insulin therapy, permanent laboratory testing is required. If sugar levels become decreased or increased, the use of Gatilin should be discontinued and it is necessary to consult your doctor.

Like other quinolones, gatifloxacin should be used with caution in case of central nervous system pathology in the anamnesis such as mental illness, epilepsy, severe cerebral atherosclerosis (risk of circulatory disorders, stroke), in which the development of convulsions may occur.

Tendonitis and tendon rupture.

Tendonitis and tendon rupture (not limited to the Achilles tendon), sometimes bilateral, may occur within 48 hours after starting treatment with quinolones and fluoroquinolones and, as reported, even for several months after discontinuation of treatment. The risk of tendonitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients with whole-organ transplants, and patients treated concomitantly with corticosteroids. Thus, concomitant use of corticosteroids should be avoided.

At the first signs of tendonitis (e.g., painful swelling, inflammation), the drug therapy should be discontinued and alternative treatment should be considered. The affected limb(s) should be treated appropriately (e.g., immobilization). Corticosteroids should not be used in case of signs of tendinopathy.

Peripheral neuropathy.

In patients treated with quinolones and fluoroquinolones, cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia, or weakness have been reported. In the event of symptoms of neuropathy, such as pain, burning, tingling, numbness, or weakness, patients treated with the medicinal product should inform their physician to prevent the development of a potentially irreversible condition. Quinolones can also stimulate the nervous system, which is manifested by tremors, insomnia, seizures, hallucinations, paranoia, depression, and nighttime delirium. These reactions may occur with the first dose. In this case, the drug therapy should be discontinued.

When quinolones are used, serious anaphylactic reactions may occur, some reactions are accompanied by cardiovascular collapse, arterial hypotension/shock, convulsions, loss of consciousness, tinnitus, angioedema (including tongue, throat, larynx, face), acute respiratory distress, dyspnea, urticaria, pruritus, and other serious skin reactions. In case of these symptoms, the drug therapy should be discontinued and appropriate measures should be taken (oxygen, antihistamines, corticosteroids, pressor amines).

When taking antibiotics the intestinal flora changes and Clostridium difficile may be induced. As a result antibiotic-associated colitis may occur.

The development of pseudomembranous colitis of varying severity has been reported with antibacterial drugs, including gatifloxacin.

Do not drink alcohol during treatment with gatifloxacin.

Avoid exposure to ultraviolet rays due to the high risk of photosensitization.

Gatifloxacin solution should not be used if it is cloudy or if there is a residue. If the container is damaged, i.e., sterility is compromised, the solution should not be used. Use the prepared gatifloxacin solution immediately after preparation.

The rate of intravenous administration is 400 mg of gatifloxacin over 40 to 60 minutes.

 

Pregnancy and lactation.

The use is contraindicated.

If gatifloxacin therapy is required, breastfeeding should be discontinued.

 

Effects on ability to drive and use machines.

Psychomotor reaction speed may be impaired; therefore, patients should refrain from driving or operating precision machinery during treatment.

 

Method of administration and dosage.

Skin tolerance test should be performed before using the preparation.

The drug should be administered every 24 hours by intravenous drip. The dosage and duration of treatment depend on the type and severity of infection.

Exacerbation of chronic bronchitis – 400 mg once a day for 5-7 days.

Acute sinusitis - 400 mg once a day for 10 days.

Community acquired pneumonia – 400 mg once a day for 7-14 days.

Uncomplicated urinary tract infections – 400 mg once or 200 mg once a day for 3 days.

Complicated urinary tract infections, pyelonephritis – 400 mg once a day for 7-10 days.

Uncomplicated urethral gonorrhea in men and uncomplicated vaginal and rectal gonorrhea in women – 400 mg single application.

Dose adjustment for patients with renal insufficiency.

Since gatifloxacin is mainly excreted by the kidneys, patients with creatinine clearance < 40 ml/min, including patients undergoing hemodialysis or long-term outpatient peritoneal dialysis, require dose adjustment.

The following dosages are recommended for patients with renal insufficiency:

Creatinine clearance	Initial dose	Next dose
> 40 ml/min	400 mg	400 mg every day
< 40 ml/min	400 mg	200 mg every day
Hemodialysis	400 mg	200 mg every day
Long-term outpatient peritoneal dialysis	400 mg	200 mg every day

Chronic hepatic failure.

There is no need to adjust the dose regimen of Gatilin for patients with impaired liver function.

The medicinal product should be used by intravenous infusion only. It is not intended for intramuscular, intra-rectal, intraperitoneal or subcutaneous use. Infusion should be continued for 60 minutes.

 

Children.

There is a lack of experience to use the medicinal product for patients under 18 years of age.

 

Overdose.

Clinical symptoms of overdose: changes in the central nervous system such as confusion, dizziness, convulsive seizures and psychosis may occur. Patients should be monitored thoroughly (including ECG). In case of gatifloxacin overdose, a gastric lavage is needed. The patient should receive symptomatic and supportive care. It is necessary to initiate an appropriate hydration therapy considering the patient’s state.

In case of gatifloxacin overdose, hemodialysis is ineffective: approximately 14% of the administered dose is excreted from the blood within 4 hours, and 11% – by using continuous outpatient peritoneal dialysis within 8 days.

 

Adverse reactions.

The most common side effects of the medicinal product are dizziness, vomiting, diarrhea, vaginitis, abdominal pain and headache. In addition, other adverse reactions may occur.

Immune system disorders: fever, anaphylactic reactions, vasculitis, eczema, angioedema.

Skin and subcutaneous tissue disorders: skin rash, itching, photosensitization, phototoxicity, hyperhidrosis, dry skin, Stevens-Johnson syndrome.

Nervous system disorders*: agitation, consciousness disturbance, nervousness, restlessness, anxiety, sleep disorder, insomnia, drowsiness, paresthesia, nightmares or paranoia, tremor, seizures, dizziness, depression, neuropathy.

Ear and labyrinth disorders*: tinnitus, ototoxicity.

Eye disorders*: visual function disorders.

Cardiovascular system disorders: palpation, peripheral edema, chest pain, prolongation of QT interval on ECG, vasodilatation, arterial hypertension or arterial hypotension, syncope.

Gastrointestinal disorders: abdominal pain, anorexia, constipation, dyspepsia, bloating, diarrhea, glossitis, gastritis, oral candidiasis, stomatitis, mouth ulcer, heartburn, flatulence, vomiting, thirst, pancreatitis, dysgeusia.

Musculoskeletal and connective tissue disorders*: arthropathy, arthralgia, myalgia, convulsions, tendinitis, tendovaginitis, increased risk of tendon rupture.

Hepatobiliary system disorders: increased liver enzymes, cholestatic jaundice, hepatitis.

Endocrine system disorders: changes in blood sugar concentrations (hypoglycemia (including hypoglycemic coma), hyperglycemia).

Renal and urinary system disorders: renal dysfunction, including acute renal failure, crystalluria, transient nephritis, dysuria and hematuria occur rarely.

Respiratory system disorders: dyspnea, pharyngitis.

Other disorders*: asthenia, back pain, headache, chest pain.

Investigations: neutropenia, increased levels of ALT, AST, alkaline phosphatase, bilirubin, amylase, disturbed electrolytes levels, increased prothrombin time, thrombocytopenia.

Other adverse reactions may occur due to the use of gatifloxacin in mono-or combination therapy: thinking disturbances, disturbance in alcohol tolerance, arthritis, asthma (bronchospasm), ataxia, bradycardia, colitis, cyanosis, depersonalization, ecchymosis, nosebleed, euphoria, photosensitivity, gingivitis, hostility, hallucinations, uterine bleeding, hyperesthesia, lymphadenopathy, maculopapular rash, myasthenia, rectal hemorrhage, stress, substernal pain, vesicular bullous rash.

* In very rare cases, patients treated with quinolones and fluoroquinolones, regardless of risk factors, have experienced prolonged (months or years), disabling, and potentially irreversible serious adverse reactions affecting various and sometimes multiple body systems and sensory organs (including tendonitis, tendon rupture, arthralgia, limb pain, gait disturbance, paresthesia-related neuropathy, depression, fatigue, memory impairment, sleep disorders, and hearing, vision, taste, and smell disorders).

 

Shelf-life. 3 years.

 

Storage conditions.

Store in a dry place at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

 

Packaging.

100 ml in a container. 1 container with instructions for medical use in a carton.

 

Terms of dispensing.

On prescription.

 

Date of last update.

05.03.2025