Leflock-Darnitsa

APPROVED

By the Order of the Ministry of Health of Ukraine 02.10.2019 No. 2004

Marketing Authorization No. UA/14011/01/01

PACKAGE LEAFLET

for medical use of medicinal product

LEFLOK-DARNITSA

Qualitative and quantitative composition:

active substance: levofloxacin;

1 ml of solution contains levofloxacin hemihydrate equivalent to levofloxacin 5 mg

excipients: sodium chloride, hydrochloric acid dilute, sodium hydroxide, water for injections.

Pharmaceutical form .Solution for infusion

Basic physicochemical properties: clear yellow liquid with green tone.

Pharmacotherapeutic group.

Quinolone antibacterials. Fluoroquinolones. Code: АТC J01M А12.

Pharmacological properties.

Pharmacodynamic properties.

Levofloxacin – synthetical antimicrobial from fluoroquinolones group, S-enantiomer of racemic substance for drug of ofloxacin. Operating as an antimicrobial drug from fluoroquinolones the levofloxacin affects the complex of DNA- DNA- gyrase and topoisomerase IV. The principal mechanism of resistibility is the result of mutation in gyr-A genes.

In vitro there is a perfect resistibility between levofloxacin and other fluoroquinolones.

Boundary values

Recommended by the European Committee for Antimicrobial Sensitivity Testing (EUCAST), the MIC

limit values for levofloxacin separating susceptible micro-organisms from intermediately susceptible organisms (moderately resistant) and intermediate-sensitive from resistant organisms, present in Table 1 the test MIC (mg/l).

Clinical EUCAST MIC for levofloxacin:

Table 1

Pathogen	Susceptible	Resistant
Enterobacteriaceae	≤ 1 mg/l	> 2 mg/l
Pseudomonas spp.	≤ 1 mg/l	> 2 mg/l
Acinetobacter spp.	≤ 1 mg/l	> 2 mg/l
Staphylococcus spp.	≤ 1 mg/l	> 2 mg/l
S. pneumoniae 1	≤ 2 mg/l	> 2 mg/l
Streptococcus A, B, C, G	≤ 1 mg/l	> 2 mg/l
H. influenzae 2, 3	≤ 1 mg/l	> 1 mg/l
M. catarrhalis 3	> 1 mg/l	> 1 mg/l
Non-species boundary values 4	≤ 1 mg/l	> 2 mg/l

_{1 Limit values of levofloxacin refer to high-dose therapy}

_{2 Low levels of resistance to fluoroquinolones (MIC of ciprofloxacin 0.12-0.5 mg/l) are possible, but there is no evidence that such resistance is clinically relevant for respiratory tract infections caused by H. influenzae.}

_{3 Strains with MIC values higher than the cut-off value between sensitive and intermediate-sensitive (moderately resistant) strains are very rare or have not yet been reported. The identification and antimicrobial susceptibility tests of any such isolate should be repeated and, if confirmed, the isolate sent to an authorized laboratory. If there is evidence of a clinical response for confirmed MIC isolates above the current resistance threshold, they should be reported as resistant.}

_{4 Limit values for oral doses of 500 mg once up to 500 mg x 2 times a day and intravenous doses of 500 mg once up to 500 mg x 2 times a day.}

Antibacterial range

Prevalence of resistibility for selected types can vary geographically and in time. It is desirable to get local information about resistibility, especially when treating serious infections.

Usually sensitive types

Aerobian gram-positive bacteria: Staphylococcus methicillin-susceptible S. aureus*, Staphylococcus saprophyticus, Streptococci, С and G group, Streptococcus agalactiae, Streptococcus pneumoniae*, Streptococcus pyogenes*.

Aerobian gram-negative bacteria: Burkholderia cepacia**, Eikenella corrodens, Haemophilus influenzae*, Haemophilus para-influenzae*, Klebsiella oxytoca, Klebsiella pneumoniae*, Moraxella catarrhalis*, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.

Anaerobic bacteria: Peptostreptococcus.

Other: Chlamydophila pneumoniae*, Chlamydophila psittaci, Chlamidia trachomatis, Legionella pneumophila*, Mycoplasma pneumoniae*, Mycoplasma hominis, Ureaplasma urealyticum.

The types whose acquired (secondary) resistance can be a problem.

Aerobian gram-positive bacteria: Enterococcus faecalis*, Staphylococcus aureus, Staphylococcus coagulase spp.

Aerobian gram-negative bacteria: Acinetobacter baumannii*, Citrobacter freundii*, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae*, Escherichia coli*, Morganella morganii*, Proteus mirabilis*, Providencia stuartii, Pseudomonas aeruginosa*, Serratia marcescens*.

Anaerobic bacteria: Bacteroides fragilis, Bacteroides ovatus**, Bacteroides thetaiotamicron**, Bacteroides vulgatus**, Clostridium difficile**.

Naturally resistant strains

Aerobian gram-positive bacteria: Enterococcus faecium.

_{* Clinical response was demonstrated for sensitive isolates in approved clinical indications.}

_{** Natural moderate sensitivity.}

Other data

Hospital infections, induced by Pseudomonas aeruginosa, can require a combination therapy.

Pharmacokinetics properties

Absorption

There are no substantial differences in pharmacokinetics of levofloxacin after intravenous and perioral use. After intravenous introduction the agent in accumulated in mucosa of bronchus and bronchialis secretion of lungs (concentration in lungs exceeds the said in blood plasma), urina. Levofloxacin poorly gets into cerebrospinal fluid.

Distribution

Approximately 30‑40 % of levofloxacin relates to serum protein of blood. Accumulation effect of Levofloxacin repeated use in dosage of 500 mg once per 24 hours practically is absent. There is an insignificant but supposed accumulation effect after using 500 mg twice per 24 hours. The stable state is gained within 3 days.

Penetration into tissues and fluids of the body

Penetration into mucosa of bronchus, bronchialis secret secretion of lungs tissues.

The maximum concentration of levofloxacin in bronchial mucosa and bronchial secretion of the lung after perioral use of 500 mg was 8.3 μg/g and 10.8 μg/ml, respectively. These indicators were achieved within 1 hour after taking the drug.

Penetration into lung tissue

The maximum concentrations of levofloxacin in the lung tissues after perioral use of 500 mg were approximately 11.3 μg/g and were achieved 4-6 hours after application of the drug. Concentration in the lungs exceeds that in the blood plasma.

Penetration into bladder content

Maximum concentrations of levofloxacin (4.0‑6.7 μg/ml) into the bladder content were achieved 2‑4 hours after use of the drug for 3 days of application in doses of 500 mg 1 time or 2 times a day, respectively.

Penetration into the cerebrospinal fluid (spinal fluid)

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After use of 500 mg of levofloxacin once a day for 3 days, the average concentrations in the prostate tissue reached 8.7 μg/g, 8.2 μg/g and 2 μg/g, respectively 2 hours, 6 hours and 24 hours, the average concentration ratio of prostate/plasma was 1.84.

Concentration in urine

The average concentration in the urine 8‑12 hours after a single perioral dose of 150 mg or 300 mg or 500 mg of levofloxacin was 44 mg/L, 91 mg/L and 200 mg/L, respectively.

Biotransformation

Levofloxacin is metabolized to an insignificant degree, metabolites are dysmethyl-levofloxacin and levofloxacin N-oxide. These metabolites make less than 5% of the amount of the drug excreted in the urine. Levofloxacin is stereochemically stable and is not subject to inversion of the chiral structure.

Excretion

After perioral and intravenous administration, levofloxacin is removed from the blood plasma relatively slowly (period of semi-excretion is 6‑8 hours). It is excreted mainly by kidneys (85 % of the administered dose).

There are no significant differences in the pharmacokinetics of levofloxacin after intravenous and perioral administration, indicating that the perioral and intravenous routes of administration are interchangeable.

Linearity

Levofloxacin has a linear pharmacokinetics in the range of 50‑600 mg.

Patients with renal failure

The pharmacokinetics of levofloxacin is affected by renal failure. With a decrease in kidney function, renal excretion and clearance are reduced, and periods of semi-excretion are increased, as can be seen from the following Table 2:

Table 2

Creatinine clearance (ml/min)	< 20	20‑49	50‑80
Renal clearance (ml/min)	13	26	57
Semi-excretion period (h)	35	27	9

Elderly age patients

There are no significant differences in the pharmacokinetics of levofloxacin in young patients and elderly patients, except for differences associated with creatinine clearance.

Gender differences

Separate analysis by groups of female and male patients showed slight differences in the pharmacokinetics of levofloxacin, depending on sex. There is no evidence that these differences in pharmacokinetics are clinically significant.

Clinical particulars.

Therapeutic indications.

Leflock-Darnitsa, a solution for infusion, is prescribed for adults for the treatment of such infectious diseases caused by levofloxacin susceptible microorganisms:

- non-hospital pneumonia*;

- complicated skin and soft tissue infections*;

- acute pyelonephritis and complicated urinary tract infections;

‑ chronic bacterial prostatitis;

- pulmonary form of anthrax: post-contact prophylaxis and radical treatment.

_{* with respect to the above infectious diseases, levofloxacin should only be prescribed in cases where the efficacy of other antibacterial medicinal products, which are predominantly used for the initial treatment of these infections, is insufficient.}

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Contraindications.

• Hypersensitivity to levofloxacin, other quinolones, to any component of the drug.
• Adverse reactions from the tendons after the previous use of quinolones.
• Epilepsy.
• In children or adolescents under 18 years of age.
• Period of pregnancy or lactation.

Interaction with other medicinal products and other forms of interactions.

Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs (NSAIDs)

It is possible to significantly reduce the convulsive threshold with the simultaneous use of quinolones and theophylline, NSAIDs and other substances that reduce the convulsive threshold. The concentration of levofloxacin in presence of fenbufen is approximately 13 % higher than when taking only levofloxacin.

Probenecid and cimetidine

Probenecid and cimetidine statistically significantly affect the excretion of levofloxacin. The renal clearance of levofloxacin decreases in the presence of probenecid by 34 %, and of cimetidine by 24 %. Therefore, both drugs can block tubular excretion of levofloxacin. They should be used with caution in patients with renal impairment

Cyclosporine

The semi-excretion period of cyclosporine is increased by 33 % when administered simultaneously with levofloxacin.

Vitamin K antagonist

At simultaneous application with antagonists of vitamin K (for example with warfarin) values of coagulation tests (PV/international normalization ratio) increase. Severe bleeding is possible. Therefore, patients receiving concurrent antagonists of vitamin K, it is necessary to monitor coagulation rates.

Drugs that extend the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution for patients who receive drugs that extend the QT interval (including antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides, antipsychotics).

Theophylline

Levofloxacin does not affect the pharmacokinetics of theophylline, which is predominantly metabolized by CYP1A2, so it can be considered that levofloxacin is not an inhibitor of CYP1A2.

Glucocorticoids

When used simultaneously with glucocorticoids, the risk of developing a tendon tear increases.

Other

There is no clinically significant effect on the pharmacokinetics of levofloxacin when levofloxacin is used together with the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.

It is not recommended to use levofloxacin concomitantly with alcohol.

Special warnings and precautions for use.

Patients who have experienced serious adverse reactions in the past with quinolones or fluoroquinolones should be avoided. Treatment of these patients with levofloxacin should only be started in the absence of alternatives and after careful benefit/risk assessment.

Prolonged, debilitating and potentially irreversible serious adverse reactions

In very rare cases, patients receiving fluoroquinolones, regardless of age and available risk factors, have reported prolonged (for months or years) disabling and potentially irreversible serious adverse reactions that affect different, and sometimes several, at once body systems (motion, nervous, psyche and sense organs). The drug should be discontinued immediately after the onset of the first signs or symptoms of any serious adverse reaction and should seek medical advice.

Patients with severe renal impairment, as well as severe atherosclerosis of cerebral vessels, disorders of the cerebral circulation should be cautious when using the drug.

During treatment, it is necessary to monitor the function of the kidneys and liver.

When using the drug, you should refrain from drinking.

In the very severe course of pneumonia caused by pneumococci, levofloxacin may not produce the optimal therapeutic effect.

Hospital infections caused by Pseudomonas aeruginosa may require combination therapy.

Duration of introduction

The recommended duration of administration of the drug is at least 60 minutes for 500 mg solution for infusion. Regarding ofloxacin it is known that tachycardia and a temporary increase in blood pressure may occur during infusion. In rare cases, a sudden decrease in blood pressure, circulatory collapse may occur. If a marked decrease in blood pressure is observed with levofloxacin administration, it should be discontinued immediately.

Aortic aneurysm and stratification

Epidemiological studies indicate an increased risk of aneurysm and aortic stratification after administration of fluoroquinolones, especially in the elderly.

Therefore, fluoroquinolones should only be used after careful benefit/risk assessment and after considering other treatment options in patients with a difficult family history of aneurysm disease or in patients with aortic aneurysm and/or stratification of the aorta, or in the presence of risk factors, or with or without risk factors. aneurysm and aortic stratification (e. g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu artery, giant cell arteritis, Behcet's disease, arterial hypertension, established atherosclerosis).

In case of sudden abdominal pain, chest or back pain, patients should be advised to seek immediate medical attention from the emergency room.

Methicillin-resistant staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus is likely to have cross-resistance to fluoroquinolones, levofloxacin. Therefore, levofloxacin is not recommended for the treatment of known or suspected MRSA infections, unless the results of laboratory tests have confirmed the sensitivity of the pathogen to levofloxacin.

E. coli resistance

The resistance of E. coli, the most common pathogen of urinary tract infections, to fluoroquinolones varies in different countries of the European Union. When prescribing levofloxacin, physicians should consider the local prevalence of E. coli resistance to fluoroquinolones.

Pulmonary form of anthrax

Clinical practice is based on studies of the sensitivity of Bacillus anthracis in vitro, as well as experimental data from animal studies, together with limited human research data. Doctors should use agreed national and/or international documents for the treatment of anthrax.

Tendonitis and tendon rupture

Tendonitis and tendon ruptures (not limited to Achilles tendons), sometimes bilateral, may occur as early as 48 hours after initiation of quinolone and fluoroquinolone treatment and have been reported even within months of discontinuation of patients receiving 1000 mg daily doses of lexicon. The risk of tendonitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients with transplantation of whole organs and patients treated with corticosteroids. Therefore, the concomitant use of the drug with corticosteroids should be avoided.

At the first signs of tendinitis (for example, painful swelling, inflammation), treatment should be discontinued, and alternative treatment considered. The damaged limb(s) should be treated properly (e. g. by providing immobilization). Corticosteroids should not be used in the event of signs of tendinopathy.

Diseases caused by Clostridium difficile

Diarrhea, especially severe, persistent, or with blood impurities during or after treatment with levofloxacin, may be a symptom of a disease caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, levofloxacin should be discontinued immediately and appropriate treatment initiated (e. g., vancomycin). Means that suppress intestinal motility are contraindicated in this clinical situation.

Patients with a tendency to convulsion

Quinolones can lower the seizure threshold and provoke seizure development. Levofloxacin is contraindicated in patients with a history of epilepsy.

Like other quinolones, the drug should be used with extreme caution in patients who are susceptible to seizures, such as patients with central nervous system disease, with simultaneous treatment with fenbufen and similar medicines or drugs that increase seizure (lowering seizure). as theophylline (see section "Interactions with other medicinal products and other types of interactions"). Treatment with levofloxacin should be discontinued in the event of a seizure.

Glucose-6-phosphate dehydrogenase deficiency

Patients with latent or advanced glucose-6-phosphate dehydrogenase activity are prone to hemolytic reactions when treated with quinolone antibacterial drugs, so levofloxacin should be used with caution in such patients.

Kidney failure

Because levofloxacin is predominantly excreted by the kidneys, dosage adjustment is required for patients with renal insufficiency (see section “Dosage and administration”).

Hypersensitivity reactions

Levofloxacin can occasionally cause severe potentially fatal hypersensitivity reactions (e. g., angioedema, anaphylactic shock), even after first use. If hypersensitivity reactions occur, it is necessary to discontinue levofloxacin, consult a physician, and initiate appropriate treatment.

Severe bullous reactions

Severe bullous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with levofloxacin administration. If bullous reactions occur, levofloxacin should be discontinued immediately, a physician should be consulted, and appropriate treatment initiated.

Change in blood glucose

Changes in blood glucose (hyperglycemia and hypoglycemia) have been reported with the use of quinolones, especially in patients with diabetes who were simultaneously taking oral hypoglycemic agents (including glibenclamide) or insulin. There were cases of hypoglycemic coma. Patients with diabetes need blood glucose monitoring.

Prevention of photosensitivity reactions

Photosensitivity reactions during treatment with levofloxacin have been reported. In order to prevent photosensitivity reactions, patients receiving levofloxacin should avoid sunlight and UV rays (artificial UV lamps, tanning beds) while taking levofloxacin and within 48 hours of discontinuing levofloxacin.

Patients using vitamin K antagonists should monitor blood clotting rates when co-administered with levofloxacin and vitamin K antagonists (warfarin) because of the potential risk of increased blood clotting rates (prothrombin time/MHV) and/or bleeding.

Psychotic reactions

Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare cases, they have progressed to suicidal ideation and self-destructive behavior, sometimes only after receiving a single dose of levofloxacin. If these reactions occur in the patient, the use of levofloxacin should be discontinued, and appropriate measures taken. It is recommended to use levofloxacin with caution in patients with psychotic disorders and patients with a history of psychiatric illness.

QT lengthening

When receiving fluoroquinolones, cases of QT prolongation have been reported. Caution should be exercised when administering fluoroquinolones, including levofloxacin, to patients with known risk factors for QT prolongation:

- syndrome of congenital or acquired prolonged QT interval.

- simultaneous use of drugs that prolong the QT interval (including antiarrhythmic drugs class IA and III, tricyclic antidepressants, macrolides, antipsychotic drugs);

- electrolyte balance disturbance (hypokalemia, hypomagnesemia);

- heart disease (heart failure, myocardial infarction, bradycardia).

Elderly patients are more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in this group of patients.

Peripheral neuropathy

In patients receiving quinolones and fluoroquinolones, cases of sensory or sensorimotor polyneuropathy have been reported leading to paresthesia, hypesthesia, dysesthesia, or weakness. In the event of symptoms of neuropathy, such as pain, burning, tingling, numbness or weakness, patients treated with the drug should tell their doctor to prevent the development of a potentially irreversible condition.

Hepatobiliary disorders

Cases of hepatic necrosis have been reported with levofloxacin up to life-threatening liver failure, mainly in patients with severe underlying conditions such as sepsis (see section “Adverse reactions”). Patients should be advised to discontinue treatment and consult a physician if they present with anorexia, jaundice, dark urine, itching, or abdominal pain.

Exacerbation of myasthenia gravis

Fluoroquinolones, including levofloxacin, block neuromuscular transmission and can provoke muscle weakness in patients with myasthenia gravis. Serious adverse reactions, including fatalities and the need for respiratory support, have been reported with fluoquinolone in the post-registration period in patients with myasthenia gravis. Levofloxacin is not recommended for patients with a history of myasthenia gravis.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately

Superinfection

The use of levofloxacin, especially for a long time, can lead to excessive growth of insensitive to the action of the microorganism drug. If superinfection develops during therapy, appropriate measures should be taken.

Interference with laboratory tests

In patients treated with levofloxacin, the determination of opiates in the urine may produce a false positive result. It may be necessary to confirm positive results for opiates using more specific methods.

Levofloxacin can inhibit the growth of Mycobacterium tuberculosis, so a false-negative result in bacteriological testing in patients with tuberculosis is possible.

Important information about excipients

This medicine contains 860 mg/dose of sodium. Caution should be exercised when administering the product to patients who follow a sodium-controlled diet.

Fertility, pregnancy and lactation.

Due to the lack of research and possible damage to the articular cartilage by quinolones in the body that grows, the drug is contraindicated for use during pregnancy and lactation. If pregnancy occurs during treatment with the drug, this should be reported to the doctor.

Levofloxacin caused no impairment of fertility or reproductive performance in animal.

Effects on ability to drive and use machines.

Some undesirable effects (e. g. dizziness/vertigo, drowsiness, visual disturbances) may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).

Posology and method of administration.

The dosage depends on the type and severity of the infection, as well as the sensitivity to the possible pathogen.

The drug should be given slowly intravenously 1–2 times daily by drip infusion. The duration of administration of 1 vial of levofloxacin (100 ml intravenous solution with 500 mg of levofloxacin) should be at least 60 minutes.

Mixing with solutions for infusions

The drug is compatible with such solutions for infusion:

0.9 % sodium chloride solution, 5 % glucose monohydrate, 2.5 % dextrose in Ringer's solution, multicomponent solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

The solution should be used within 3 hours after punching the vial.

Treatment with levofloxacin after initial administration of its intravenous form may be completed by oral administration, provided that such treatment is acceptable to the patient. Given the bioequivalence of parenteral and oral dosage forms, the same dose can be administered.

The duration of treatment depends on the course of the disease. As with other antibacterial agents, it is recommended that the drug be continued for at least 48–72 hours after normalization of body temperature or confirmed by microbiological tests for the destruction of pathogens.

Dosage for adult patients with normal renal function who have a creatinine clearance greater than 50 ml/min are shown in Table 3.

Table 3

Indication	Daily dose, (mg)	Daily dose regimen	Total duration of treatment1
non-hospital pneumonia	500	1−2	7–14 days
complicated urinary tract infections	500	1	7–14 days
acute pyelonephritis	500	1	7–10 days
chronic bacterial prostatitis	500	1	28 days
complicated skin and soft tissue infections	500	1−2	7–14 days
pulmonary form of anthrax	500	1	8 weeks

_{1 In accordance with the patient's condition, a transition from the initial intravenous administration of levofloxacin to perioral administration with the same dosage is possible in a few days.}

Since levofloxacin is excreted mainly by the kidneys, the dose should be reduced for patients with impaired renal function.

Dosage for adult patients with impaired renal function, where the creatinine clearance is less than 50 ml/min, are shown in Table 4.

Table 4

Creatinine clearance (ml/min)	Dosing mode (depending on the severity of infection and nosological form)
	250 mg/24 h	500 mg/24 h	500 mg/12 h
	First dose: 250 mg	First dose: 500 mg	First dose: 500 mg
50-20	Following: 125 mg/24 h	Following: 250 mg/24 h	Following: 250 mg/12 h
19-10	Following: 125 mg/48 h	Following: 125 mg/24 h	Following: 125 mg/12 h
< 10 (including hemodialysis and CAPD1)	Following: 125 mg/48 h	Following: 125 mg/24 h	Following: 125 mg/24 h

_{1 No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).}

Dosing for patients with impaired liver function

Correction of the dose is not required, since levofloxacin is to a small extent metabolized in the liver.

Dosage for elderly patients

If the kidney function is not impaired, there is no need for dose adjustment.

Children.

The drug is contraindicated for use in children, since articular cartilage is possible.

Overdose.

Symptoms: dizziness, disturbance / confusion, convulsions, tremors, QT lengthening.

Treatment: In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Hemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body. No specific antidote exists.

Undesirable effects.

Adverse reactions indicated on the system and frequencies: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

In each group, adverse reactions were presented in order of decreasing severity.

Eye disorders*: rare – visual disturbances, blurred vision, temporary loss of sight

Ear and labyrinth disorders*: uncommon – vertigo; rare – noise in the ears; not known – hearing disorder, hearing loss.

Respiratory, thoracic and mediastinal disorders: uncommon – shortness of breath; not known –

bronchospasm, allergic pneumonitis.

Gastrointestinal disorders: common – diarrhea, nausea, vomiting; uncommon – abdominal pain, indigestion, bloating, constipation; not known – diarrhea hemorrhagic, which may indicate enterocolitis, including pseudomembranous colitis, pancreatitis.

Hepatobiliary disorders:  common – ed liver enzymes (ALT/AST, alkaline phosphatase, GGTP); uncommon – increased bilirubin; not known – jaundice and severe liver damage, including cases of acute hepatic insufficiency, mainly in patients with severe basic diseases, hepatitis

Renal and urinary disorders:  uncommon – increased serum creatinine; not known – acute renal failure (e. g. due to interstitial nephritis).

Metabolism and nutrition disorders:  uncommon – anorexia; rare – hypoglycemia, especially in patients with diabetes; not known – hyperglycemia, hypoglycemic coma. Signs of hypoglycemia can be increased appetite, nervousness, increased sweating, trembling of the limbs.

Nervous system disorders*: common – headache, dizziness; uncommon – numbness, drowsiness, tremor, dysgeusia; rare – convulsions, paresthesia; not known – peripheral sensory or sensorimotor neuropathy, decreased sense of touch; parosmia, including anosmia, agevia, dyskinesia, extrapyramidal disorders, other movement coordination disorders, including walking, fainting, benign intracranial hypertension.

Psychiatric disorders*: common – insomnia; uncommon – agitation, confusion, irritability; rare – psychotic disorders (including hallucinations, paranoia), depression, anxiety, anxiety, jelly, pathological dreams, nightmares; not known – psychotic reactions with self-destructive behavior, including suicidal tendencies of thinking or actions (see section "Special warnings and precautions for use").

Cardiac disorders: rare – tachycardia, palpitation; not known – ventricular tachycardia, which can lead to cardiac arrest; ventricular arrhythmia and arrhythmia of the torsade de pointes type (predominantly in patients with risk factors for prolonging the QT interval) prolongation of the QT interval on the ECG, hypotension, collapse, vasculitis, phlebitis.

Blood and lymphatic system disorders: uncommon – leukopenia, eosinophilia; rare – neutropenia, thrombocytopenia, which causes an increased tendency to extravasation or bleeding.; not known – agranulocytosis, pancytopenia, hemolytic anemia.

Immune system disorders: rare – angioedema, hypersensitivity reactions, including anaphylactic shock, anaphylactoid shock (anaphylactic and anaphylactoid reactions can sometimes occur even after the first dose).

Skin and subcutaneous tissue disorders: uncommon – angioedema, hives, reddening of skin, itching, urticaria, hyperhidrosis; not known – exudative erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity, hypersensitivity to sun and ultraviolet radiation, leukocytoplastic vasculitis, stomatitis.

Musculoskeletal and connective tissue disorders*: uncommon – arthralgia, myalgia; rare – tendon involvement, including their inflammation (tendinitis) (e. g. Achilles tendon), muscle weakness, which may be of particular importance for patients with severe myasthenia gravis; not known – rhabdomyolysis, tear of tendons, ligaments, muscles, arthritis.

Infections and invasions: uncommon – fungal infections, including fungi of the genus Candida, reproduction of other resistant microorganisms.

General disorders and administration site conditions*: common – changes at the injection point, including redness, pain; uncommon – asthenia; rare – general weakness; increased body temperature; pain (including pain in the back, chest and extremities); as with the use of other fluoroquinolones, porphyria attacks are possible in patients with porphyria.

_{* In very rare cases, patients receiving quinolones and fluoroquinolones, regardless of the available risk factors, have reported prolonged (for months or years), disabling and potentially irreversible serious adverse reactions that affect different, and sometimes several, organism systems. sensory organs (including reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy associated with paresthesia, depression, fatigue, memory impairment, sleep disturbance, hearing impairment, vision, taste) and odor).}

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after registration of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk ratio for the respective drug. Healthcare providers should be informed of any suspected adverse reactions through the national alert system.

Shelf life .3 years.

Special precautions for storage.

Do not store above 25 ºC. Store in the original package. Do not freeze.

Keep out of reach of children.

Incompatibilities.

The solution should not be mixed with heparin or alkaline solutions (e.g. sodium hydrogencarbonate), with other medicines.

Nature and contents of container.

100 ml in a bottle; 1 bottle in a pack or without it.

Category of release.

Prescription only medicine.

Manufacturer.

PrJSC "Pharmaceutical firm "Darnitsa".

The manufacturer's location and address of the place of business

13, Boryspilska Street, Kyiv, 02093, Ukraine.