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

Composition:

Active substance: ofloxacin;

100 ml of solution contain 200 mg of ofloxacin;

Excipients: sodium chloride, disodium edetate, concentrated hydrochloric acid, sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, colorless to slightly yellow solution.

Pharmacotherapeutic group. Antibacterial agents for systemic use. Fluoroquinolones. ATC code J01MA01.

Pharmacological Properties

Pharmacodynamics

Ofloxacin is a synthetic broad-spectrum antimicrobial agent of the fluoroquinolone class.

At concentrations equal to or slightly higher than the minimum inhibitory concentration (MIC), it exerts a bactericidal effect by inhibiting DNA gyrase—an enzyme essential for bacterial DNA replication and transcription.

The antimicrobial spectrum includes: Gram-negative and Gram-positive bacteria sensitive to ofloxacin: Enterobacteriaceae (Escherichia coli, species of Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, Yersinia), Pseudomonas spp., including Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus ducreyi, Branhamella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Acinetobacter spр., Campylobacter spр., Gardnerella vaginalis, Helicobacter pylori, Pasteurella multocida, Vibrio spр., Brucella melitensis; staphylococci, including penicillinase-producing strains and some methicillin-resistant strains; it is also active against Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Ureaplasma urealyticum (at borderline MIC values), Mycobacterium tuberculosis, Mycobacterium leprae, and some other mycobacteria.

Streptococci of groups A, B, and C exhibit borderline sensitivity.

Most anaerobes, with the exception of Clostridium perfringens, are resistant.

Ofloxacin is inactive against Treponema pallidum.

Pharmacokinetics

Ofloxacin penetrates tissues and distributes well into body fluids, including cerebrospinal fluid. Relatively high concentrations are achieved in bile. The volume of distribution is 1.5–2.5 L/kg. Plasma protein binding is approximately 25%.

Ofloxacin is partially metabolized to desmethyl-ofloxacin and ofloxacin-N-oxide. Desmethyl-ofloxacin has weak antimicrobial activity.

The plasma half-life of ofloxacin is approximately 5–8 hours. In renal impairment, it is prolonged depending on the severity of the condition to 15–60 hours. Ofloxacin is primarily eliminated by the kidneys via tubular secretion and glomerular filtration. Within 24–48 hours, 75–80% of the administered dose is excreted unchanged in urine, less than 5% as metabolites. 4–8% of the administered dose is excreted in feces. Elimination of ofloxacin may be delayed in patients with severe hepatic impairment (e.g., cirrhosis). Renal clearance of ofloxacin is 173 mL/min and total clearance is up to 214 mL/min, independent of dose. Only a small fraction can be removed by hemodialysis (15–25%); the biological half-life during hemodialysis is approximately 8–12 hours. During peritoneal dialysis, the biological half-life is 22 hours.

Ofloxacin exhibits a post-antibiotic effect.

Clinical characteristics.

Indications.

Infectious and inflammatory diseases caused by microorganisms sensitive to ofloxacin:

exacerbation of chronic obstructive pulmonary disease (including chronic bronchitis)*, community-acquired pneumonia*;
uncomplicated acute cystitis*, urethritis*, acute pyelonephritis, and complicated urinary tract infections;
complicated skin and soft tissue infections*.

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

*when it is not possible to use other antibacterial agents commonly used for treatment of these infections.

Contraindications.

Hypersensitivity to ofloxacin, other components of the drug, or other agents of the fluoroquinolone group;
epilepsy;
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;
children or adolescents during growth phase, as well as pregnant or breastfeeding women, since experimental data in animals indicate that a negative effect on the joint cartilage of growing organisms cannot be completely excluded.

Ofloxacin must not be administered to patients with QT interval prolongation, patients with uncompensated hypokalemia, or patients receiving class IA (quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmic agents.

Interaction with other medicinal products and other forms of interaction.

Like other fluoroquinolones, ofloxacin should be used with caution in patients receiving drugs known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section "QT interval prolongation" under "Special precautions for use***"***).

Increased bleeding time has been reported when ofloxacin is used concomitantly with anticoagulants.

The risk of neurotoxic effects increases when ofloxacillin is used together with nonsteroidal anti-inflammatory drugs (NSAIDs), nitroimidazole derivatives, and methylxanthines.

Concomitant use with glucocorticosteroids increases the risk of tendon rupture, particularly in elderly patients.

Simultaneous administration of ofloxacin and procainamide may lead to elevated procainamide levels in patients; careful monitoring of plasma procainamide levels and ECG is required, and dosage adjustment may be necessary.

A sudden drop in blood pressure may be observed in individual cases when ofloxacin is used concomitantly with antihypertensive agents or anesthetic barbiturates.

If quinolones are taken simultaneously with other drugs that lower the seizure threshold, such as theophylline, an additional decrease in the cerebral seizure threshold may occur. However, ofloxacin, unlike some other fluoroquinolones, is not considered to have pharmacokinetic interactions with theophylline.

An additional decrease in the cerebral seizure threshold may also occur when ofloxacin is used concomitantly with certain NSAIDs and other agents that lower the seizure threshold.

If seizures occur, ofloxacin should be discontinued.

Ofloxacin may cause a slight increase in serum concentrations of glyburide (glibenclamide); careful monitoring of patients receiving this combination is recommended.

Renal elimination of quinolones may be impaired and serum levels increased when administered simultaneously with other drugs undergoing tubular secretion (e.g., probenecid, cimetidine, furosemide, and methotrexate).

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

Mycobacterium tuberculosis is moderately susceptible to ofloxacin, which may lead to false-negative results in bacteriological diagnosis of tuberculosis.

Close monitoring is required when insulin, caffeine, theophylline, cimetidine, cyclosporine, NSAIDs, anticonvulsants, or drugs metabolized by cytochrome P450 are administered concomitantly.

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.

Special precautions for use.

The use of the drug should be avoided in patients who have previously experienced serious adverse reactions to quinolones or fluoroquinolones (see section "Adverse reactions"). Treatment with ofloxacin in these patients should be initiated only when there are no alternative treatment options and after careful assessment of benefit/risk (see also section "Contraindications").

If the patient's condition permits, it is recommended to switch to treatment with appropriate doses of ofloxacin tablets.

The drug should be discontinued immediately in case of development of allergic reactions or pronounced adverse effects on the central nervous system (CNS).

The drug should be administered with caution in patients with CNS disorders (severe atherosclerosis of cerebral vessels, history of acute cerebral circulation insufficiency), and in patients with impaired renal function.

Patients with acute hepatic insufficiency should not exceed a dose of 400 mg per day.

Patients should drink sufficient amounts of fluid to avoid crystalluria.

Ofloxacin should be administered only by slow intravenous infusion over 60 minutes. Rapid or bolus injections may lead to arterial hypotension. Ofloxacin is not a first-line agent for the treatment of pneumococcal or mycoplasma pneumonia, or acute tonsillitis caused by β-hemolytic streptococci.

If ofloxacin is administered intravenously concomitantly with antihypertensive agents, a sudden drop in blood pressure may occur. In such cases, or when the drug is administered concomitantly with barbiturate anesthetics, monitoring of cardiovascular function is required.

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

Infections caused by Escherichia coli

Resistance of E. coli—the most common cause of 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 N. gonorrhoeae, ofloxacin should not be used as an empirical approach to antibacterial therapy in suspected gonococcal infection (gonococcal urethritis, pelvic inflammatory disease, epididymo-orchitis), except 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 the treatment of pelvic inflammatory disease, ofloxacin should be used only in combination with agents active against anaerobic microorganisms.

Hypersensitivity and allergic reactions

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 for shock).

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"). In case of skin and/or mucosal reactions, patients should be advised to contact their physician immediately before continuing treatment.

Clostridium difficile-associated disease

Diarrhea during or after ofloxacin treatment (including several weeks after treatment), especially if severe, persistent, 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"). Therefore, this diagnosis should be considered in patients who develop severe diarrhea during or after ofloxacin treatment. If pseudomembranous colitis is suspected, ofloxacin should be discontinued immediately. Appropriate specific antibiotic therapy should be initiated promptly (e.g., oral vancomycin, oral teicoplanin, or metronidazole). In this clinical situation, drugs that inhibit intestinal motility are contraindicated.

Patients with predisposition to seizures

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.

Prolonged, disabling, and potentially irreversible serious adverse reactions

In very rare cases, patients receiving quinolones and fluoroquinolones, regardless of age or existing risk factors, have reported prolonged (lasting months or years), disabling, and potentially irreversible serious adverse reactions affecting various systems of the body, sometimes multiple systems simultaneously (e.g., musculoskeletal, nervous, psychiatric, and sensory organs). The drug should be discontinued immediately upon the first signs or symptoms of any serious adverse reaction, and medical advice should be sought.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (not limited to the Achilles tendon), sometimes bilateral, may occur within 48 hours of starting quinolone or fluoroquinolone therapy and have been reported even several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients with organ transplants, and patients receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

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

Patients with impaired renal function

The drug should be administered with caution in patients with impaired renal function. Dose and dosing interval adjustments are necessary in patients with renal insufficiency and in elderly patients due to delayed elimination (see section "Dosage and administration").

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, including:

uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
congenital long QT syndrome;
acquired QT prolongation;
cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia);
concomitant use of medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
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.

Aortic aneurysm and dissection, and valvular regurgitation/incompetence

Epidemiological studies indicate 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 valvular regurgitation/incompetence 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 therapies in patients with a history of aneurysm or congenital valvular heart disease, or in patients diagnosed with aortic aneurysm and/or aortic dissection or valvular heart disease, or in the presence of other risk factors:

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

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

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

Patients should be advised to seek immediate medical attention if they experience acute dyspnea, new onset of rapid heartbeat, or development of abdominal or lower limb edema.

Patients with history of psychiatric 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. If such reactions occur, ofloxacin should be discontinued and appropriate therapeutic measures taken. Ofloxacin should be used with caution in patients with a history of psychiatric disorders or mental illness.

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 contact their physician if symptoms or signs of liver disease occur, such as anorexia, jaundice, dark urine, pruritus, or abdominal tenderness on palpation (see section "Adverse reactions").

Patients taking vitamin K antagonists

Due to possible elevation of coagulation parameters (prothrombin time/international normalized ratio (INR)) and/or bleeding in patients receiving fluoroquinolones, including ofloxacin, in combination with vitamin K antagonists (e.g., warfarin), monitoring of coagulation parameters is required when these two drug groups are used concomitantly (see section "Interaction with other medicinal products and other forms of interaction").

Myasthenia

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 photosensitivity have been reported with ofloxacin use (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 photosensitivity.

Superinfection

Antibiotic use, especially over prolonged periods, may lead to overgrowth of resistant microflora; therefore, the patient's condition 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, hypoesthesia, 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 inform their physician to prevent the development of potentially irreversible conditions (see section "Adverse reactions").

Dysglycemia

Disturbances in blood glucose levels, including both hyperglycemia and hypoglycemia, have been reported during use of quinolones, including ofloxacin, particularly in diabetic patients receiving concomitant therapy with 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 (see section "Adverse reactions").

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 administered with caution in these patients, with monitoring for potential hemolysis.

Visual disturbances

If any visual disturbances or adverse reactions affecting the eyes occur during ofloxacin administration, immediate consultation with an ophthalmologist is required (see sections "Effect on ability to drive and use machines" and "Adverse reactions").

Effect on laboratory test results

False-positive results in urine opiate or porphyrin tests may occur during ofloxacin treatment. More specific methods may be required to confirm positive opiate or porphyrin test results.

Patients with rare hereditary disorders

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

The medicinal product contains 365.47 mg of sodium per dose; therefore, caution should be exercised when administering to patients on a sodium-restricted diet.

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 possibility of arthropathy and other serious toxicities in the breastfed infant, breastfeeding should be discontinued during ofloxacin treatment.

Effect on ability to drive and use machines.

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

Since drowsiness, impaired ability to operate machinery, dizziness, and visual disturbances have been reported in individual cases after drug administration, patients should be aware of their individual response to ofloxacin before driving or operating machinery.

Method of Administration and Dosage.

For use in adults. Administer by intravenous infusion. Prior to initiation of infusion, a skin allergy test should be performed.

The physician determines the dose of ofloxacin individually, depending on the susceptibility of microorganisms, type and severity of the infectious process.

Exacerbation of chronic obstructive pulmonary disease (including chronic bronchitis), community-acquired pneumonia: 200 mg twice daily.

Uncomplicated acute cystitis, urethritis, acute pyelonephritis, and complicated urinary tract infections: 200 mg twice daily.

Complicated skin and soft tissue infections: 400 mg twice daily.

The infusion time should be no less than 30 minutes for each 200 mg. Individual doses should generally be administered at equal intervals. The dose of 400 mg twice daily may be used in severe or complicated infections.

Dosing in patients with renal impairment. Patients with impaired renal function may require dose reduction depending on creatinine clearance. If creatinine clearance is 20–50 mL/min, the dose should be reduced to 100–200 mg every 24 hours. When creatinine clearance is < 20 mL/min, the dose should be 100 mg every 24 hours. For patients undergoing hemodialysis or peritoneal dialysis, the ofloxacin dose should be 100 mg every 24 hours.

The duration of ofloxacin treatment depends on the type of infection and clinical response. After normalization of body temperature and improvement in the patient's general condition, treatment should be continued for an additional 3 days.

In most cases of acute infection, the duration of treatment is 7–10 days. The physician may switch the patient from parenteral to oral administration without changing the dose.

The total duration of treatment should not exceed 2 months.

Children.

The drug is contraindicated in children and adolescents.

Overdose.

The most significant expected signs of acute overdose include symptoms related to the central nervous system (CNS), such as dizziness, disorientation, drowsiness, confusion, lethargy, seizures, QT interval prolongation, as well as gastrointestinal reactions such as nausea, vomiting, and erosive mucosal damage.

There is no specific antidote. Treatment is symptomatic. Ofloxacin is primarily excreted by the kidneys (75–80% of the administered dose is excreted unchanged in urine within 24–48 hours). Elimination can be accelerated by forced diuresis. Hemodialysis removes only a limited amount of ofloxacin (on average 15–25%), and peritoneal dialysis removes less than 2%.

ECG monitoring is required due to the potential for QT interval prolongation. Antacids are recommended to protect the gastric mucosa.

Adverse Reactions

The adverse reactions listed below are classified by organ systems and frequency of occurrence. Frequency of occurrence is categorized as follows: 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), frequency not known (cannot be estimated from the available data).

Infections and parasitic diseases: uncommon – fungal infections; resistance of pathogenic organisms.

Blood and lymphatic system disorders: very rare – anaemia, haemolytic anaemia; leucopenia, eosinophilia; thrombocytopenia; frequency not known – agranulocytosis, bone marrow dysfunction.

Immune system disorders: rare – hypersensitivity reactions, including anaphylactic/anaphylactoid reactions**, angioedema** (including tongue, larynx, pharynx swelling, swelling/face puffiness); very rare – anaphylactic/anaphylactoid shock**.

Metabolism and nutrition disorders: rare – anorexia; frequency not known – hypoglycaemia in diabetic patients taking antidiabetic agents, hyperglycaemia, hypoglycaemic coma.

Psychiatric disorders*: uncommon – agitation, sleep disturbances, insomnia; rare – psychotic disorders (e.g. hallucinations); restlessness, confusion, nightmares, depression, delirium; frequency not known – psychotic disorders and depression with self-destructive behaviour, including suicidal thoughts or suicide attempts, nervousness.

Nervous system disorders*: uncommon – dizziness, headache; rare – somnolence, paraesthesia, dysgeusia, parosmia; very rare – peripheral sensory neuropathy**, peripheral sensorimotor neuropathy**, muscle seizures**, extrapyramidal symptoms or other muscle coordination disorders; frequency not known – tremor, dyskinesia, ageusia (loss of taste sensation), syncope, benign intracranial hypertension.

Eye disorders*: uncommon – eye mucous membrane irritation; rare – visual disturbances; frequency not known – uveitis.

Ear and labyrinth disorders*: uncommon – vertigo; very rare – tinnitus, hearing loss; frequency not known – hearing impairment.

Cardiac disorders**: rare – tachycardia; frequency not known – ventricular arrhythmias, polymorphic ventricular tachycardia of the torsades de pointes type (these reactions have been reported mainly in patients with risk factors for QT interval prolongation); QT interval prolongation on ECG.

Vascular disorders**: common – phlebitis; rare – arterial hypotension; frequency not known – tachycardia and arterial hypotension may occur during ofloxacin infusion. In very rare cases, such hypotension may be severe.

Respiratory, thoracic and mediastinal disorders: uncommon – cough, nasopharyngitis; rare – dyspnoea, bronchospasm; frequency not known – allergic pneumonitis, severe dyspnoea.

Gastrointestinal disorders: uncommon – abdominal pain, diarrhoea, nausea, vomiting; rare – enterocolitis, sometimes haemorrhagic; very rare – pseudomembranous colitis*; frequency not known – dyspepsia, flatulence, constipation, pancreatitis.

Hepatobiliary disorders: rare – increased levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase and/or alkaline phosphatase), increased blood bilirubin levels; very rare – cholestatic jaundice; frequency not known – hepatitis, which may sometimes be severe**, severe liver damage has been reported, including cases of fatal acute liver failure, primarily in patients with severe underlying liver diseases (see section "Special precautions").

Skin and subcutaneous tissue disorders: uncommon – pruritus, rash; rare – urticaria, flushing, increased sweating, pustular rash; very rare – erythema multiforme, toxic epidermal necrolysis, photosensitivity reactions**, drug dermatitis, vasculitis, vasculitis which in exceptional cases may lead to skin necrosis; frequency not known – Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, drug rash, stomatitis, exfoliative dermatitis.

Musculoskeletal and connective tissue disorders*: rare – tendinitis; very rare – arthralgia, myalgia, tendon ruptures (particularly Achilles tendon), which may be bilateral and occur within 48 hours of starting treatment; frequency not known – rhabdomyolysis and/or myopathy, muscle weakness, muscle strain, muscle rupture, ligament rupture, arthritis.

Renal and urinary disorders: rare – increased serum creatinine levels; very rare – acute renal failure; frequency not known – acute interstitial nephritis.

Congenital, familial and genetic disorders: frequency not known – porphyria attacks in patients with porphyria.

General disorders and administration site conditions*: common – infusion site reaction (pain, redness); frequency not known – asthenia, pyrexia, pain (including back, chest and limb pain).

* Cases of very rare, prolonged (several months or years), disabling and potentially irreversible serious adverse reactions affecting various, and sometimes multiple, organ systems have been reported (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disturbances, hearing impairment, visual disturbances, taste and smell disturbances), associated with the use of quinolones and fluoroquinolones, regardless of the presence of risk factors (see section "Special precautions").

** Data from post-marketing surveillance.

*** 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”).

Description of selected adverse reactions

Anxiety, suicidal thoughts, panic attacks, neuralgia, and attention disturbances have been reported with fluoroquinolone use as potential features of prolonged and disabling adverse reactions.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions.

Store at temperatures not exceeding 25 ºC in the original packaging.

Keep out of the reach of children.

Unused medicine should be destroyed.

Incompatibilities.

Ofloxacin solution must not be mixed with heparin and other infusion solutions except those with which ofloxacin compatibility has been studied.

When administered with drugs that alkalinize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

The medicine is compatible with the following infusion solutions: 0.9% sodium chloride solution, Ringer's solution, and 5% glucose solution.

Packaging. 100 ml of the product in a container, 1 container in a polyvinyl chloride film, together with the instructions for medical use in a carton.

Prescription category. Prescription only.

Manufacturer.

Euro Life Healthcare Pvt. Ltd.

Manufacturer's address and place of business.

Plot No. 520, Bhagwanpur, Roorkee, Haridwar, Uttarakhand, India.

Marketing Authorisation Holder.

Ananta Medikare Ltd.

Address of the Marketing Authorisation Holder and/or its representative.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.