Ofloxacin euro

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OFLOXACINEURO

Composition:

Active substance: ofloxacin;

1 tablet contains 200 mg or 400 mg of ofloxacin;

Excipients: lactose monohydrate, sodium croscarmellose, maize starch, magnesium stearate, hydroxypropylmethylcellulose, hydroxypropylcellulose, titanium dioxide (E 171), talc, polyethylene glycol 6000.

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties:

200 mg tablets: white or almost white, round, biconvex film-coated tablets;

400 mg tablets: white or almost white, capsule-shaped, biconvex film-coated tablets.

Pharmacotherapeutic group. Antimicrobials for systemic use. Fluoroquinolones. ATC code J01MA01.

Pharmacological Properties

Pharmacodynamics

A broad-spectrum antimicrobial agent of the fluoroquinolone group. The bactericidal effect of ofloxacin is associated with inhibition of bacterial DNA gyrase enzyme. Highly active against most Gram-negative bacteria: Escherichia coli, Salmonella spp., Shigella spp., Proteus spp., Morganella morganii, Klebsiella spp. (including Klebsiella pneumoniae), Enterobacter spp., Serratia spp., Citrobacter spp., Yersinia spp., Providencia spp., Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Mycoplasma spp., Legionella pneumophila, Acinetobacter spp., as well as Chlamydia spp. Also active against some Gram-positive microorganisms (including Staphylococcus spp., Streptococcus spp.). Enterococcus faecalis, Streptococcus pneumoniae, Pseudomonas spp., and anaerobic bacteria (except Bacteroides ureolyticus) are less susceptible to ofloxacin. Active against bacteria producing beta-lactamases.

Pharmacokinetics

Absorption. After oral administration, ofloxacin is rapidly and easily absorbed from the gastrointestinal tract. Maximum plasma concentration of ofloxacin is reached within 1–2 hours. The bioavailability of the drug is 96–100%.

Distribution. Approximately 25% bound to plasma proteins. Ofloxacin penetrates through the placenta and is excreted into breast milk.

Metabolism. About 5% of ofloxacin undergoes metabolism. Eliminated within 5–8 hours. Up to 80% of ofloxacin is excreted unchanged by the kidneys.

Pharmacokinetics in special clinical cases. Elimination of ofloxacin may be delayed in patients with hepatic or renal impairment.

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, or central nervous system (CNS) disorders with lowered 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 drug should not be administered to patients with QT interval prolongation, uncompensated hypoglycemia, or to patients who are concurrently using medicinal products capable of prolonging the QT interval (antiarrhythmic agents of class IA and III, tricyclic antidepressants, macrolides, antipsychotics).

Interaction with other medicinal products and other types of interactions.

Concomitant use of quinolones with medicinal products that reduce seizure threshold, such as theophylline, may result in additional reduction of cerebral seizure threshold, although ofloxacin is considered not to exhibit pharmacokinetic interaction with theophylline, unlike some other fluoroquinolones.

Concomitant administration of ofloxacin with antihypertensive agents may lead to sudden decrease in arterial pressure. In such cases, or when ofloxacin is used during barbiturate anesthesia, monitoring of cardiovascular function is required.

Concomitant use of ofloxacin with nonsteroidal anti-inflammatory drugs (including phenylpropionic acid derivatives), nitroimidazole derivatives, and methylxanthines increases the risk of nephrotoxic effects and reduction of seizure threshold, which may lead to seizures.

Possible interactions when ofloxacin is used concomitantly with other medicinal products include:

• with warfarin or its derivatives – prothrombin time or other appropriate coagulation tests should be monitored to assess blood coagulation status;
• with medicinal products known to prolong the QT interval (e.g., antiarrhythmic agents of classes IA and III, tricyclic antidepressants, macrolides, antipsychotics) – additional QT interval prolongation; concomitant use is contraindicated;
• antacids, sucralfate, metal cations – antacids containing aluminum/magnesium, sucralfate, zinc or iron preparations may reduce absorption of ofloxacin; therefore, ofloxacin should be taken at least 2 hours before administration of these products;
• with nonsteroidal anti-inflammatory drugs, medicinal products known to reduce seizure threshold (e.g., theophylline) – additional reduction in cerebral seizure threshold; if seizures occur, ofloxacin should be discontinued; ofloxacin is considered not to exhibit 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 (hypo- or hyperglycemia); blood glucose levels should be continuously 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.

When used concomitantly with urine-alkalinizing agents (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

Effect on laboratory test results. During treatment with ofloxacin, false-positive results in urine tests for opioids or porphyrins may occur. Confirmation of positive test results for opioids or porphyrins using specific methods may be necessary.

Vitamin K antagonists. Careful monitoring of coagulation parameters is required in patients taking vitamin K antagonists due to possible enhancement of the effect of coumarin derivatives. Cases of increased coagulation test parameters [prothrombin time/international normalized ratio (INR)] and/or bleeding, which could be severe, have been reported in patients receiving ofloxacin in combination with vitamin K antagonists (e.g., warfarin).

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

With high-dose administration, increased serum concentration of the drug is possible.

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

Special precautions for use

There have been reports (22 cases worldwide) of retinal detachment associated with the use of fluoroquinolone antibiotics. If visual disturbances occur during or after administration of the drug, patients should immediately consult a physician.

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

Alcoholic beverages should not be consumed during treatment.

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

The drug should be administered with caution in patients with CNS disorders (e.g., significant atherosclerosis of cerebral vessels, history of acute cerebral circulation disorders), renal impairment. Patients should drink sufficient fluids to prevent crystalluria.

Dosage and dosing intervals should be adjusted in patients with renal insufficiency and 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 beta-hemolytic streptococci.

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

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 treatment of known or suspected MRSA infections, except when laboratory results confirm susceptibility of the microorganism to ofloxacin (and when antibacterial agents typically recommended for MRSA infections cannot be used).

Infections caused by Escherichia coli

Resistance of Escherichia coli — the most common causative agent of urinary tract infections — to fluoroquinolones varies across European Union countries. 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, therapy should be re-evaluated.

Pelvic inflammatory disease

For 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 with ofloxacin use (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 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 ofloxacin treatment, especially if severe, prolonged, and/or with 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 treatment. If pseudomembranous colitis is suspected, ofloxacin should be immediately discontinued. Appropriate specific antibiotic therapy should be initiated promptly (e.g., oral vancomycin, oral teicoplanin, or metronidazole). In this clinical situation, antiperistaltic agents 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.

Patients with hypotension

In case of severe arterial hypotension, the drug should be discontinued.

QT interval prolongation

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

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

Elderly patients and younger 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, exposure to intense sunlight and ultraviolet radiation (e.g., mercury-quartz lamps, solariums) should be avoided unless absolutely necessary.

Tendinitis

Tendinitis occurs rarely but may lead to tendon rupture, particularly of the Achilles tendon. Tendinitis and tendon ruptures, sometimes bilateral, may occur within 48 hours after ofloxacin administration or even several months after discontinuation.

The risk of tendinitis and tendon rupture is increased in elderly patients and in patients receiving corticosteroids concomitantly with this medicinal product. If tendinitis is suspected, ofloxacin should be discontinued immediately and appropriate therapeutic measures initiated for the affected tendon (e.g., immobilization).

Patients with hepatic impairment

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

Patients receiving 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), monitoring of coagulation parameters is recommended when these two groups of medicinal products 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.

Phototoxicity prevention

Cases of photosensitization have been reported with ofloxacin use (see section "Adverse reactions"). Patients taking ofloxacin should avoid exposure to intense sunlight and ultraviolet radiation (e.g., mercury-quartz lamps, solariums) 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.

During ofloxacin treatment, as with other agents in this group, resistance in some strains of Pseudomonas aeruginosa may develop rapidly.

Peripheral neuropathy

Peripheral sensory or sensorimotor neuropathy has been reported in patients receiving fluoroquinolones, including ofloxacin. If neuropathy symptoms occur, ofloxacin should be discontinued to prevent irreversible damage.

Patients experiencing symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness should inform their physician immediately to prevent potentially irreversible conditions (see section "Adverse reactions").

Dysglycemia

Changes 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 prone to hemolytic reactions during quinolone therapy. Therefore, ofloxacin should be prescribed with caution in such patients.

Patients with rare hereditary disorders

This medicinal product should not be administered to patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Aneurysm/aortic dissection and cardiac valve regurgitation/incompetence

Epidemiological data suggest an increased risk of aortic aneurysm or dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/incompetence of any cardiac valve 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 therapeutic options in patients with a positive family history of aneurysm or congenital heart valve defects, or in patients with existing diagnoses of aneurysm and/or aortic dissection, or heart valve disease, or in the presence of other risk factors or predisposing conditions:

• for both aortic aneurysm/dissection and cardiac valve regurgitation/incompetence (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis), or additionally
• for aortic aneurysm/dissection (e.g., vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome), or additionally
• for cardiac valve regurgitation/incompetence (e.g., infective endocarditis). The risk of aortic aneurysm and dissection and their rupture may be increased in patients receiving systemic corticosteroids concomitantly.

In case of sudden abdominal pain, chest pain, or back pain, patients should seek immediate emergency medical assistance.

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

Visual disturbances

If any visual disturbances or adverse reactions affecting the eyes occur during ofloxacin administration, patients should immediately consult an ophthalmologist (see sections "Ability to affect reaction rate when driving or operating machinery" and "Adverse reactions").

Effect on laboratory test results

False-positive results for urinary opiates or porphyrins may occur during ofloxacin treatment. More specific methods may be required to confirm positive opiate or porphyrin test results.

Important information on excipients

The medicinal product contains sodium; therefore, patients on a sodium-restricted diet should use it with caution.

Use during pregnancy or breastfeeding

Animal studies have shown damage to articular cartilage in immature animals, but teratogenic effects were absent. 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 treatment.

Ability to affect reaction rate when driving or operating machinery

Patients are advised to refrain from activities requiring psychomotor speed (e.g., driving, operating potentially hazardous machinery), considering possible adverse reactions affecting the nervous system. If adverse reactions affecting the nervous system or vision occur, driving or operating complex machinery should be avoided.

Administration and Dosage

The medicinal product should be administered 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 dosage 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 daily doses should be divided into two equal doses administered at regular intervals.

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

Administer 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
Hemodialysis / peritoneal dialysis	normal	100 mg* every 24 hours

* Administer the drug in the appropriate dosage.

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

In cases where creatinine clearance cannot be measured, it can be calculated from serum creatinine using the following Cockcroft formula for adults:

Weight (kg) × (140 ‒ age (years))

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

72 × serum creatinine (mg/dL)

or

Weight (kg) × (140 ‒ age (years))

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

0.814 × serum creatinine (μmol/L)

For women: ClCr (mL/min) = 0.85 × (value in men)

Patients with hepatic impairment

Drug elimination may be reduced in patients with severe hepatic dysfunction. Therefore, the daily dose should not exceed 400 mg.

Elderly patients

Dose 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 lasts 7–10 days, except for uncomplicated gonorrhea, for which a single 400 mg dose is recommended.

The total duration of treatment should not exceed 2 months.

Children

The medicinal product should not be used in children.

Overdose.

Symptoms. The most significant expected signs of acute overdose are symptoms related to the central nervous system (CNS), including confusion, dizziness, disturbances of 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 to eliminate unabsorbed ofloxacin should be taken, 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 is required due to the potential for QT interval prolongation.

Adverse Reactions

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

Skin and subcutaneous tissue disorders: hypersensitivity reactions (usually with skin manifestations), drug-induced dermatitis, pruritus, rash; urticaria, blistering, flushing, hyperhidrosis, pustular eruptions; erythema multiforme, vasculitis, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), acute generalized exanthematous pustulosis; photosensitization, photosensitivity reactions resembling sunburn, skin discoloration, or nail separation.

Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema (including tongue, larynx, pharynx swelling, facial swelling or puffiness), anaphylactic/anaphylactoid shock; skin eruptions (including pustular, hemorrhagic), pruritus; urticaria; flushing; hyperhidrosis; erythema; Lyell's syndrome; photosensitization reactions; drug-induced dermatitis; vasculitis; Stevens-Johnson syndrome; acute generalized exanthematous pustulosis; drug rashes; exfoliative dermatitis; skin hyperpigmentation; nail discoloration or separation. Immediately after administration of ofloxacin, anaphylactic/anaphylactoid reactions may develop, including signs of anaphylaxis, tachycardia, fever, dyspnea, shock, angioedema, vasculitis (which in rare cases may lead to necrosis), eosinophilia. In such cases, the drug should be discontinued and alternative therapy initiated.

Endocrine system disorders: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Cardiovascular system disorders**: tachycardia, transient hypotension, collapse (if severe hypotension develops, treatment with the drug should be discontinued); ventricular arrhythmia, ventricular flutter (mainly observed in patients with risk factors for QT interval prolongation on ECG), QT interval prolongation; hypertension, cerebral thrombosis, cardiac arrest, shock.

Psychiatric disorders*: agitation, sleep disturbances, 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, spatial disorientation, rarely delirium.

Nervous system disorders*: headache, dizziness, depression with self-destructive behavior, including suicidal ideation or suicide attempts, epileptic seizures, sleep disturbances, insomnia, somnolence, restlessness, excitement, convulsions, confusion, loss of consciousness, night terrors, slowed reaction time, increased intracranial pressure, paresthesia; peripheral sensory or peripheral sensorimotor neuropathy, tremor and other extrapyramidal symptoms, muscle coordination disorders (impaired sense of balance, unsteady gait), psychotic reactions, hallucinations, vertigo, ataxia, exacerbation of myasthenia gravis, dysgeusia, parosmia.

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

Hepatobiliary disorders: elevated levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase, and/or alkaline phosphatase) and bilirubin; jaundice (including cholestatic, parenchymal); hepatitis; necrosis. Severe liver injury has been reported, including cases of fatal acute liver failure, primarily in patients with severe underlying liver disease.

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

Reproductive system and breast disorders: irritation, burning, and painful eruptions on the external genital organs in women. Vaginitis, dysmenorrhea, hypermenorrhea, and metrorrhagia may also occur.

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

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

Sensory organ disorders*: photophobia, color vision defects; cases of retinal detachment have been reported (see section "Special Warnings and Precautions for Use"), eye mucous membrane irritation; vertigo; visual, taste, and smell disturbances; conjunctivitis; nystagmus; decreased visual acuity; visual disturbances (including diplopia, photophobia); tinnitus; hearing loss; dizziness; decreased hearing acuity; motor coordination disorders; uveitis.

Respiratory, thoracic and mediastinal disorders: cough; nasopharyngitis; dyspnea; bronchospasm; allergic pneumonitis; severe wheezing; shortness of breath; rhinorrhea; wheezing; allergic pulmonitis; sensation of air hunger; respiratory arrest.

Metabolism and nutrition disorders: hypoglycemia or hyperglycemia (in diabetic patients taking antidiabetic medications), elevated plasma triglycerides, cholesterol, and potassium levels, acidosis, hypoglycemic coma (see section "Special Warnings and Precautions for Use").

Infections: vaginitis, fungal infections, candidiasis, resistance in pathogenic microorganisms.

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

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

* Very rare cases of prolonged (lasting several months or years), disabling, and potentially irreversible serious adverse reactions affecting various organ systems (including tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances, neuropathy associated with paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, taste, and smell disorders) have been reported, sometimes regardless of the presence of risk factors (see section "Special Warnings and Precautions for Use"); anxiety, suicidal ideation, panic attacks, neuralgia, and concentration difficulties have also been reported as potential features of long-term, disabling adverse reactions associated with fluoroquinolones.

** 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 Warnings and Precautions for Use").

Reporting of suspected adverse reactions after drug registration is of great importance. It allows ongoing monitoring of the benefit-risk balance of the drug. Healthcare professionals, pharmacists, and patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging.

Tablets 200 mg: 10 tablets in a blister; 1 blister in a cardboard box.

Tablets 400 mg: 5 tablets in a blister; 1 blister in a cardboard box.

Prescription category. Prescription only.

Manufacturer. FDS Limited.

Manufacturer’s address and location of business operations.

L-56/57, Phase II-D, Verna Industrial Estate, Verna, Salcette, Goa - 403 722, India.