Ofloxacin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OFLOXACIN (OFLOXACIN)

Composition:

active substance: ofloxacin;

1 tablet contains 0.2 g of ofloxacin;

excipients: lactose monohydrate, potato starch, magnesium stearate, stearic acid, sodium croscarmellose.

Pharmaceutical form. Tablets.

Main physico-chemical properties: white tablets with a yellowish tint.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Antibacterial agents of the quinolone group. Ofloxacin. ATC code J01MA01.

Pharmacological Properties

Pharmacodynamics

A broad-spectrum antimicrobial agent of the fluoroquinolone group. The bactericidal effect of ofloxacin is due to its ability to inhibit the bacterial enzyme DNA gyrase, thereby disrupting bacterial DNA function. The antimicrobial spectrum includes most Gram-negative and some Gram-positive microorganisms.

Organisms sensitive to ofloxacin include: Staphylococcus aureus (including methicillin-resistant strains); Staphylococcus epidermidis; Neisseria gonorrhoeae; Neisseria meningitidis; Escherichia coli; Salmonella spp.; Shigella spp.; Morganella morganii; Yersinia spp.; Haemophilus influenzae; Citrobacter; Klebsiella oxytoca; Enterobacter; Hafnia; Proteus (both indole-positive and indole-negative species); Campylobacter jejuni; Aeromonas hydrophila; Plesiomonas; Vibrio cholerae; Vibrio parahaemolyticus; Chlamydia; Legionella; Helicobacter pylori; and aerobic Gram-positive bacteria—staphylococci, including penicillinase-producing strains.

Less sensitive organisms: Enterococcus; Streptococcus (S. pyogenes, S. pneumoniae, S. viridans); Serratia marcescens; Acinetobacter; Mycoplasma hominis; Mycoplasma pneumoniae; Pseudomonas aeruginosa; Mycobacterium tuberculosis; and Mycobacterium fortuitum.

Synergistic activity of ofloxacin and rifabutin against Mycobacterium leprae has been demonstrated.

In most cases, resistant organisms include anaerobic bacteria (Bacteroides, Peptococcus, Peptostreptococcus, Eubacterium, Fusobacterium, Clostridium difficile); Ureaplasma urealyticum; and Nocardia asteroides.

Ineffective against Treponema pallidum.

Pharmacokinetics

After oral administration, ofloxacin is rapidly and readily absorbed from the gastrointestinal tract (GIT). The maximum plasma concentration of ofloxacin after a single 200 mg oral dose is 2.5–3 mg/mL, reached within 1–2 hours. The bioavailability of the drug is 96–100%. Plasma protein binding is approximately 25%. Ofloxacin penetrates through the placenta and into breast milk. Approximately 5% of ofloxacin undergoes metabolism. Elimination occurs within 5–8 hours. Up to 80% of the administered dose is excreted unchanged by the kidneys. Elimination of ofloxacin may be delayed in patients with renal or hepatic impairment.

In elderly patients, administration of a single oral dose of ofloxacin results in an increased elimination half-life, while maximum serum concentration remains unchanged. In patients with renal insufficiency, elimination half-life increases proportionally to the reduction in creatinine clearance, and both total and renal clearance are reduced.

Clinical characteristics.

Indications.

Infectious and inflammatory diseases caused by microorganisms sensitive to ofloxacin:

• Exacerbation of chronic bronchitis and chronic obstructive pulmonary disease;
• Community-acquired pneumonia;
• Acute pyelonephritis and complicated urinary tract infections;
• Nongonococcal/gonococcal urethritis and cervicitis;
• Complicated skin and soft tissue infections.

This medicinal product should be used to treat the above-mentioned infections only when other antibacterial agents, typically prescribed for initial treatment of these infections, cannot be used.

Official recommendations regarding appropriate use of antibacterial agents should be taken into account.

Contraindications.

• Hypersensitivity to the active substance, other components of the medicinal product, or to other fluoroquinolones.
• Epilepsy, including history of epilepsy, central nervous system disorders with reduced seizure threshold (following head trauma, stroke, inflammatory processes of the brain and meninges).
• History of tendinitis.
• Glucose-6-phosphate dehydrogenase deficiency.
• Pregnancy and breastfeeding.

The medicinal product must not be used in patients with QT interval prolongation, uncompensated hypoglycemia, or in patients who are concurrently using medicinal products capable of prolonging the QT interval (antiarrhythmic agents of classes IA and III, tricyclic antidepressants, macrolides, antipsychotics).

Interaction with other medicinal products and other types of interactions.

When ofloxacin is used concomitantly with other medicinal products, the following interactions are possible:

with warfarin or its derivatives – prothrombin time or other appropriate coagulation tests should be monitored to assess blood coagulation status;

with medicinal products capable of prolonging the QT interval (e.g., antiarrhythmic agents of classes IA and III, tricyclic antidepressants, macrolides, antipsychotics) – additional QT interval prolongation may occur; therefore, concomitant use is contraindicated;

antacids, sucralfate, metal cations – antacids containing aluminium/magnesium, sucralfate, zinc or iron preparations may reduce ofloxacin absorption when administered concomitantly; therefore, ofloxacin should be taken at least 2 hours before administration of these agents;

with nonsteroidal anti-inflammatory drugs, medicinal products capable of reducing seizure threshold (e.g., theophylline) – additional reduction in central nervous system seizure threshold; if seizures occur, ofloxacin should be discontinued. Ofloxacin is considered not to undergo pharmacokinetic interaction with theophylline, unlike other fluoroquinolones;

with glyburide – concomitant use of ofloxacin may cause a slight increase in serum glyburide concentrations; careful monitoring of patients receiving this combination is recommended;

with antidiabetic medicinal products – fluctuations in blood glucose levels (hypoglycemia or hyperglycemia); blood glucose levels should be monitored during concomitant use;

with indirect anticoagulants – prolonged bleeding time; careful monitoring of coagulation parameters is required during concomitant use;

with medicinal products excreted via tubular secretion (e.g., probenecid, cimetidine, furosemide, methotrexate) – impaired elimination and increased plasma levels of ofloxacin.

Effect on laboratory test results: false-positive results in urine tests for opioids or porphyrins may occur during ofloxacin treatment. Confirmation of positive opioid or porphyrin test results using more specific methods may be necessary.

Vitamin K antagonists – in patients receiving ofloxacin in combination with vitamin K antagonists (e.g., warfarin), cases of increased coagulation test parameters [prothrombin time / international normalized ratio (INR)] and/or bleeding, which could be severe, have been reported.

Close monitoring of coagulation parameters is required in patients taking vitamin K antagonists due to the potential for enhanced effect of coumarin derivatives.

Ofloxacin may inhibit the growth of Mycobacterium tuberculosis and lead to false-negative results in bacteriological testing for tuberculosis diagnosis.

When high doses of the drug are used, increased serum concentrations of ofloxacin are possible.

Concomitant use of ofloxacin with caffeine, theophylline, cimetidine, cyclosporine, oral anticoagulants, and drugs metabolized via cytochrome P450 may enhance adverse effects.

Special precautions for use.

Avoid using ofloxacin in patients who have experienced serious adverse reactions in the past with quinolones or fluoroquinolones (see section "Adverse reactions"). Treatment with ofloxacin in these patients should be initiated only if no alternative treatment options are available and after careful benefit/risk assessment (see also section "Contraindications").

Alcoholic beverages are not recommended during treatment.

Patients with a history of severe adverse reactions (tendinitis, severe neurological reactions) to other quinolones have an increased risk of developing similar reactions to ofloxacin.

Use the drug with caution in patients with central nervous system disorders (severe atherosclerosis of cerebral vessels, previous acute cerebral circulation disorders) and in patients with renal impairment. Patients should drink sufficient fluids to prevent crystalluria.

Dosage and dosing intervals should be adjusted in patients with renal insufficiency and in elderly patients due to delayed elimination.

Ofloxacin is not a first-line agent for the treatment of pneumonia caused by pneumococci or mycoplasma, or acute tonsillitis caused by β-hemolytic streptococci.

Allergic and hypersensitivity reactions have been reported after administration of the initial dose of fluoroquinolones. Anaphylactic and anaphylactoid reactions may progress to life-threatening shock, even after the first dose. In such cases, ofloxacin should be discontinued immediately and appropriate treatment initiated (e.g., treatment of shock).

For methicillin-resistant S. aureus (MRSA), there is a very high likelihood of concomitant resistance to fluoroquinolones, including ofloxacin. Therefore, ofloxacin is not recommended for the treatment of known or suspected infections caused by MRSA, except when laboratory results confirm susceptibility of the microorganism to ofloxacin (and when antibacterial agents usually recommended for MRSA infections cannot be used).

Infections caused by Escherichia coli

Resistance of Escherichia coli—the most common pathogen in urinary tract infections—to fluoroquinolones varies across countries of the European Union. Prescribers are advised to consider local prevalence of E. coli resistance to fluoroquinolones.

Infections caused by Neisseria gonorrhoeae

Due to increasing resistance of Neisseria gonorrhoeae, ofloxacin should not be used for empirical antibacterial therapy in suspected gonococcal infections (gonococcal urethritis, pelvic inflammatory disease, epididymo-orchitis), but only when the pathogen has been identified and its susceptibility to ofloxacin confirmed. If no clinical improvement is observed after 3 days of treatment, the therapy should be re-evaluated.

Pelvic inflammatory disease

For the treatment of pelvic inflammatory disease, ofloxacin should be used only in combination with agents active against anaerobic microorganisms.

Severe bullous reactions

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported during ofloxacin therapy (see section "Adverse reactions"). If skin and/or mucosal reactions occur, patients should be advised to contact their physician immediately before continuing treatment.

Prolonged, disabling, and potentially irreversible serious adverse reactions

In patients receiving fluoroquinolones, regardless of age, very rare cases of prolonged (lasting several months or years), disabling, and potentially irreversible serious adverse reactions affecting various body systems (musculoskeletal, nervous, and sensory) have been reported. Ofloxacin therapy should be discontinued immediately at the first signs or symptoms of any serious adverse reaction, and medical advice should be sought.

Clostridium difficile-associated disease

Diarrhea during or after treatment with ofloxacin (including several weeks after treatment), especially if severe, persistent, and/or accompanied by bleeding, may be a symptom of pseudomembranous colitis. The severity of Clostridium difficile-associated diseases ranges from mild to life-threatening, with pseudomembranous colitis being the most severe form (see section "Adverse reactions"). It is therefore important to consider this diagnosis in patients who develop severe diarrhea during or after ofloxacin therapy. If pseudomembranous colitis is suspected, ofloxacin should be discontinued immediately. Appropriate specific antimicrobial therapy should be initiated promptly (e.g., oral vancomycin, oral teicoplanin, or metronidazole). In this clinical situation, drugs that inhibit intestinal peristalsis are contraindicated.

Patients with seizure predisposition

Quinolones may lower the seizure threshold and provoke seizures. Ofloxacin is contraindicated in patients with a history of epilepsy (see section "Contraindications"). As with other quinolones, it should be used with extreme caution in patients predisposed to seizures and in those receiving concomitant medications that lower the seizure threshold, such as theophylline (see section "Interaction with other medicinal products and other forms of interaction").

If seizures occur, ofloxacin should be discontinued.

QT interval prolongation

In very rare cases, QT interval prolongation has been reported in patients taking fluoroquinolones. Fluoroquinolones, including ofloxacin, should be used with caution in patients with risk factors for QT interval prolongation, including:

• advanced age;
• uncorrected electrolyte imbalance (hypokalemia, hypomagnesemia);
• congenital long QT syndrome;
• acquired QT prolongation;
• cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia).

Elderly patients and women may be more sensitive to drugs that prolong the QT interval. Therefore, caution should be exercised when prescribing fluoroquinolones, including ofloxacin, to these patient groups.

During treatment, avoid unnecessary exposure to intense sunlight and ultraviolet radiation (mercury-quartz lamps, tanning beds).

Aortic aneurysm and dissection, and cardiac valve regurgitation/insufficiency

Epidemiological studies have shown an increased risk of aortic aneurysm and dissection, particularly in elderly patients, as well as aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and cardiac valve regurgitation/insufficiency have been reported in patients receiving fluoroquinolones (see section "Adverse reactions").

Therefore, fluoroquinolones should be used only after careful benefit/risk assessment and consideration of alternative treatment options in patients with a history of aortic aneurysm or congenital heart valve defects, in those diagnosed with aortic aneurysm and/or dissection or heart valve disease, or in the presence of other risk factors:

• risk factors for both aortic aneurysm/dissection and cardiac valve regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome, Turner syndrome, Behçet’s disease, hypertension, rheumatoid arthritis;
• risk factors for aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren’s syndrome;
• risk factors for cardiac valve regurgitation/insufficiency: infective endocarditis.

The risk of aortic aneurysm, dissection, and rupture is increased in patients receiving systemic corticosteroids concomitantly.

Patients should seek immediate medical attention in case of sudden abdominal, chest, or back pain.

Patients should be advised to seek immediate medical help if acute dyspnea, new-onset palpitations, or development of abdominal or lower limb edema occurs.

Tendinitis and tendon rupture

Tendinitis, which may lead to tendon rupture including the Achilles tendon, may rarely occur during ofloxacin therapy. Tendinitis and tendon ruptures, sometimes bilateral, may occur within 48 hours after starting ofloxacin or even several months after discontinuation.

The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, and patients receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided. At the first signs of tendinitis (e.g., swelling, inflammation), ofloxacin should be discontinued immediately and appropriate therapeutic measures taken for the affected tendon (e.g., immobilization).

Patients with a history of psychotic disorders

Psychotic reactions have been reported in patients taking fluoroquinolones. In some cases, these reactions progressed to suicidal thoughts or self-destructive behavior, including suicide attempts, sometimes even after a single dose. If such reactions occur, ofloxacin should be discontinued and appropriate treatment initiated. Ofloxacin should be used with caution in patients with a history of psychotic disorders or psychiatric illness.

Patients with hepatic impairment

Ofloxacin should be used with caution in patients with hepatic impairment due to the potential for liver injury. Cases of fulminant hepatitis, sometimes leading to liver failure (including fatal cases), have been reported during fluoroquinolone therapy. Patients should be advised to discontinue treatment and contact their physician if symptoms or signs of liver disease occur, such as anorexia, jaundice, darkening of urine, pruritus, or abdominal tenderness on palpation.

Patients taking vitamin K antagonists

Due to the possible increase in coagulation test parameters (prothrombin time/international normalized ratio) and/or bleeding in patients receiving fluoroquinolones, including ofloxacin, in combination with vitamin K antagonists (e.g., warfarin), coagulation parameters should be monitored when these two drug groups are used concomitantly.

Myasthenia gravis

Fluoroquinolones, including ofloxacin, have neuromuscular blocking effects and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including fatal cases and conditions requiring respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis.

Ofloxacin is not recommended for use in patients with a history of myasthenia gravis.

Prevention of photosensitization

Cases of photosensitization have been reported during ofloxacin therapy (see section "Adverse reactions"). Patients taking ofloxacin should avoid exposure to intense sunlight and ultraviolet radiation (mercury-quartz lamps, tanning beds) during treatment and for 48 hours after discontinuation of the drug to prevent photosensitization.

Superinfection

Antibiotic use, especially prolonged, may lead to overgrowth of resistant microflora; therefore, patients should be monitored periodically during treatment. If secondary infection occurs, appropriate measures should be taken.

Peripheral neuropathy

Cases of peripheral sensory or sensorimotor polyneuropathy leading to paresthesia, hyposthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones (including ofloxacin). If symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, patients should be advised to inform their physician promptly to prevent development of potentially irreversible conditions (see section "Adverse reactions").

Dysglycemia

Alterations in blood glucose levels, including both hypoglycemia and hyperglycemia, have been reported with all quinolones (see section "Adverse reactions"), usually in diabetic patients receiving concomitant oral hypoglycemic agents (e.g., glyburide) or insulin. Cases of hypoglycemic coma have been reported. Diabetic patients are advised to closely monitor blood glucose levels.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or confirmed glucose-6-phosphate dehydrogenase deficiency may be susceptible to hemolytic reactions during quinolone therapy. Therefore, ofloxacin should be prescribed with caution in these patients.

Visual disturbances

If any visual disturbances or ocular adverse reactions occur during ofloxacin therapy, patients should seek immediate ophthalmological consultation (see sections "Ability to affect driving and use of machinery" and "Adverse reactions").

Effect on laboratory test results

During ofloxacin therapy, false-positive results in urine opiate or porphyrin tests may occur. More specific methods may be required to confirm positive opiate or porphyrin test results.

Patients with rare hereditary disorders

This medicinal product contains lactose monohydrate. Patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding

Animal studies have shown joint cartilage damage in immature animals, but no teratogenic effects. Therefore, ofloxacin is contraindicated during pregnancy.

Ofloxacin is excreted in breast milk in small amounts. Due to the potential for arthropathy and other serious toxicities in the breastfed infant, breastfeeding should be discontinued during ofloxacin therapy.

Ability to affect driving and use of machinery

During ofloxacin therapy, patients should refrain from activities requiring high concentration and rapid psychomotor responses (e.g., driving vehicles).

Method of Administration and Dosage.

The medicinal product should be taken orally. Tablets should be swallowed with liquid. The interval between administration of ofloxacin and administration of sucralfate, zinc or iron preparations, or aluminum/magnesium-containing antacids should be at least 2 hours, since absorption of ofloxacin may be reduced when co-administered with these agents.

Dosage.

The dose of the drug depends on the type and severity of the infectious disease. The dosage range for adults is 200 mg to 800 mg per day. Doses up to 400 mg may be administered once daily, preferably in the morning; higher doses should be taken in two divided doses evenly spaced throughout the day.

Exacerbation of chronic bronchitis and chronic obstructive pulmonary disease, community-acquired pneumonia: the drug should be administered at a dose of 400 mg once daily; if necessary, up to 400 mg twice daily.

Complicated urinary tract infections, acute pyelonephritis: the drug should be administered at a dose of 200 mg twice daily. If necessary, up to 400 mg twice daily.

Complicated skin and soft tissue infections: the drug should be administered at a dose of 400 mg twice daily.

Uncomplicated urethral or cervical gonorrhea: the drug should be administered as a single dose of 400 mg. Total course dose – 400 mg.

Urethritis and cervicitis of nongonococcal etiology: the drug should be administered at a dose of 300 mg twice daily.

Patients with renal impairment.

The drug should be administered at the usual initial dose; however, subsequent doses should be reduced according to creatinine clearance:

Creatinine clearance (plasma creatinine level)	Initial dose of the drug	Subsequent doses of the drug
20–50 mL/min (SCr – 1.5–5 mg/dL)	normal	100*–200 mg once daily
<20 mL/min (SCr – >5 mg/dL)	normal	100 mg* every 24 hours
Haemodialysis/Peritoneal dialysis	normal	100 mg* every 24 hours

* Use the drug at the appropriate dosage.

Serum ofloxacin concentrations should be monitored in patients with severe renal impairment and in patients undergoing dialysis.

When creatinine clearance cannot be measured, it can be calculated from serum creatinine using the Cockcroft formula given below for adults:

Weight (kg) × (140 ‒ age (years))

For males: ClCr (mL/min) = --------------------------------------------

72 × serum creatinine (mg/dL)

or

Weight (kg) × (140 ‒ age (years))

ClCr (mL/min) = -----------------------------------------------------

0.814 × serum creatinine (μmol/L)

For females: ClCr (mL/min) = 0.85 × (value in males)

Patients with hepatic impairment.

Drug elimination may be reduced in patients with severe hepatic impairment. Therefore, daily doses exceeding 400 mg are not recommended.

Elderly patients.

Dosage adjustment is not required (see section "Special precautions"), except in cases related to the patient's hepatic or renal function.

Duration of treatment.

The duration of treatment depends on the severity of infection and the patient's response to therapy. After normalization of body temperature and improvement in the patient's general condition, treatment should be continued for an additional 48–72 hours. The usual course of treatment is 7–10 days, except in cases of uncomplicated gonorrhea, for which a single 400 mg dose is recommended.

The duration of treatment should not exceed 2 months.

Children.

The medicinal product should not be used in children.

Overdose.

Symptoms. The most important expected signs of acute overdose are symptoms related to the central nervous system, including confusion, dizziness, impaired consciousness, seizures, hallucinations, tremor, QT interval prolongation, as well as gastrointestinal reactions such as nausea and erosive mucosal damage.

Treatment. In case of overdose, appropriate measures should be taken to eliminate unabsorbed ofloxacin, for example, gastric lavage, administration of adsorbents and sodium sulfate, preferably within the first 30 minutes after overdose. Antacids are recommended to protect gastric mucosa.

Elimination of ofloxacin can be enhanced by forced diuresis.

ECG monitoring should be performed due to possible QT interval prolongation.

Adverse Reactions

Infectious and parasitic diseases: superinfection, development of secondary infection (including fungal infections), development of resistance in pathogenic microorganisms.

Blood and lymphatic system disorders: anemia, hemolytic anemia, leukopenia, neutropenia, eosinophilia, thrombocytopenia, agranulocytosis, bone marrow suppression (which resolves after discontinuation of the drug), pancytopenia. Petechiae, bruising, and epistaxis may also occur.

Immune system, skin and subcutaneous tissue disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema (including tongue, larynx, pharynx swelling, facial swelling/edema), anaphylactic/anaphylactoid shock; skin rashes (including pustular, hemorrhagic), pruritus, urticaria, flushing, hyperhidrosis, erythema, Lyell’s syndrome, photosensitization reactions, drug-induced dermatitis, purpura, vasculitis, which may exceptionally lead to skin necrosis; Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, drug rashes, exfoliative dermatitis, skin hyperpigmentation, changes in nail color or nail separation.

Endocrine system disorders: syndrome of inappropriate antidiuretic hormone secretion.

Metabolism and nutrition disorders: hyperglycemia, hypoglycemia in patients with diabetes mellitus receiving hypoglycemic agents, increased plasma levels of triglycerides, cholesterol, and potassium, acidosis, hypoglycemic coma (see section "Special precautions").

Psychiatric disorders*: agitation, sleep disorders, insomnia, psychotic disorders (including hallucinations, paranoia, manic thoughts), restlessness, confusion, nightmares, depression, psychotic disorders and depression with self-destructive behavior, including suicidal ideation or suicide attempts; euphoria, phobias, irritability, anxiety, disorientation, rarely delirium.

Nervous system disorders*: headache, drowsiness, paresthesia, dysgeusia, parosmia, peripheral sensory neuropathy, peripheral sensorimotor neuropathy, seizures, exacerbation of myasthenia gravis, extrapyramidal disorders or other muscle coordination disturbances, development of epileptic seizures, ataxia, tremor, decreased reaction speed, increased intracranial pressure, vertigo.

Eye disorders*: eye mucous membrane irritation, conjunctivitis, nystagmus, decreased visual acuity, visual disturbances (including diplopia, photophobia), color blindness, uveitis.

Ear and labyrinth disorders*: dizziness, tinnitus, decreased hearing acuity, hearing loss, movement coordination disturbances.

Cardiovascular system disorders**: tachycardia, arterial hypotension, ventricular arrhythmias, polymorphic ventricular tachycardia of the "torsades de pointes" type (these reactions occurred predominantly in patients with risk factors for QT interval prolongation); QT interval prolongation on ECG, arterial hypertension, cerebral thrombosis, cardiac arrest, shock.

Respiratory, thoracic and mediastinal disorders: cough, nasopharyngitis, dyspnea, bronchospasm, allergic pneumonia, rhinorrhea, wheezing, allergic alveolitis, sensation of air hunger, respiratory arrest, dyspnea, severe asthma.

Gastrointestinal disorders: anorexia, abdominal pain, nausea, vomiting, diarrhea, enterocolitis (sometimes hemorrhagic), pseudomembranous colitis, dryness or burning in the mouth, dyspepsia, heartburn, flatulence, constipation, intestinal colic, intestinal perforation, intestinal bleeding, pancreatitis.

Hepatobiliary disorders: increased levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase, and/or alkaline phosphatase), increased blood bilirubin levels, jaundice (including cholestatic, parenchymatous), hepatitis. Severe liver damage has been reported, including cases of fatal acute liver failure, primarily in patients with severe underlying liver diseases. Necrosis.

Musculoskeletal and connective tissue disorders*: tendinitis, arthralgia, myalgia, tendon ruptures (including Achilles tendon), which may be bilateral and occur within 48 hours of starting treatment, rhabdomyolysis and/or myopathy, muscle weakness, muscle cramps, muscle tears, muscle ruptures, tendon pain, muscle strain.

Renal and urinary disorders: increased plasma creatinine levels, acute renal failure, acute interstitial nephritis, polyuria, dysuria, anuria, frequent urination, urinary retention, hematuria, albuminuria, candiduria, kidney stone formation.

Reproductive system and breast disorders: irritation, burning, and painful rashes on external genitalia in women. Vaginitis, dysmenorrhea, hypermenorrhea, and metrorrhagia may also occur.

Congenital, familial and genetic disorders: acute attacks of porphyria in patients with porphyria.

Other*: general weakness, increased fatigue, malaise, asthenia, edema (including pulmonary edema), back pain, fever, chills, increased pain sensitivity, weight loss, taste disturbances, smell disturbances.

* Very rare cases of long-term (lasting several months or years), disabling, and potentially irreversible serious adverse reactions affecting multiple organ systems have been reported (see section "Special precautions"). These include tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances, neuropathies manifesting as paresthesia and neuralgia, fatigue, psychiatric symptoms (including sleep disturbances, anxiety, panic attacks, depression, and suicidal thoughts), memory and concentration impairment, hearing, vision, taste, and smell disturbances. In some cases, these reactions occurred in patients without risk factors.

** Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Special precautions").

Shelf life. 3 years.

Storage conditions. Keep out of reach of children. Store in the original packaging at a temperature not exceeding 25 °C.

Packaging. 10 tablets in a blister pack, 1, 50, or 100 blisters per carton.

Prescription category. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhym-Kharkiv". PJSC "Tekhnolog".

Manufacturer's address and location of business activity.

Ukraine, 61115, Kharkiv region, city of Kharkiv, Severin Pototskogo Street, 36.

Ukraine, 20300, Cherkasy region, city of Uman, Staroproryznaya Street, 8.