Ofloxacin

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

Composition:

Active substance: ofloxacin;

100 ml of solution contains ofloxacin (calculated as 100% dry substance) 0.2 g;

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

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: clear liquid of light yellow-green or light yellow color. Theoretical osmolarity approximately 300 mosmol/L.

Pharmacotherapeutic group. Antibacterial agents of the quinolone group. Fluoroquinolones.

ATC code J01M A01.

Pharmacological properties.

Pharmacodynamics.

Ofloxacin is a synthetic antimicrobial agent of the fluoroquinolone class with broad-spectrum activity against both Gram-negative and Gram-positive organisms.

Its mechanism of action is based on inhibition of DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, leading to a bactericidal effect.

Fluoroquinolones exhibit concentration-dependent bactericidal activity and display a moderate post-antibiotic effect. Activity primarily depends on the ratio between the maximum serum concentration (Cmax) and the minimum inhibitory concentration (MIC) of the corresponding pathogen, or on the ratio between AUC (area under the pharmacokinetic curve) and MIC of the corresponding pathogen.

Mechanism of resistance

Resistance to ofloxacin and other fluoroquinolones develops through sequential mutations in the target sites of both types of topoisomerases, DNA gyrase and topoisomerase IV. Other resistance mechanisms, such as reduced cellular penetration (common in Pseudomonas aeruginosa) or enhanced cellular efflux, may also affect sensitivity to ofloxacin.

Plasmid-mediated acquired resistance has been observed in Escherichia coli, Klebsiella spp., and Enterobacteriaceae.

For ofloxacin, partial or complete cross-resistance exists with other fluoroquinolones.

Breakpoints in antimicrobial susceptibility testing

Breakpoints distinguish susceptible strains from those with intermediate susceptibility and resistant strains.

Breakpoints established by EUCAST (European Committee on Antimicrobial Susceptibility Testing):

Breakpoint MIC values (mg/l)
Microorganisms	Susceptible ≤	Resistant >
Enterobacteriaceae	0.5	1
Staphylococcus spp.	1	1 a
Streptococcus pneumoniae b	0.125	4
Haemophilus influenzae	0.5	0.5
Moraxella catarrhalis	0.5	0.5
Neisseria gonorrhoeae	0.125	0.25

a. The breakpoints refer to high-dose therapy.

b. Wild-type S. pneumoniae is considered intrinsically non-susceptible to ofloxacin; therefore, this species is generally classified as moderately susceptible.

Susceptibility

The prevalence of resistance may vary geographically and over time for individual bacterial species; therefore, local information on resistance should be sought, especially when treating severe infections. When necessary, consultation with a specialist is recommended, particularly if the local resistance prevalence raises doubts about the utility of the drug, at least for certain infections.

Usually susceptible species, including microorganisms with moderate susceptibility

Aerobic gram-positive microorganisms Bacillus anthracis, Bordetella pertussis, Corynebacterium, Streptococci.

Aerobic gram-negative microorganisms Enterobacter, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Morganella morganii, Proteus vulgaris, Salmonella, Shigella, Yersinia.

Other microorganisms Chlamydia, Chlamydophila pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae, Ureaplasma urealyticum.

Species for which acquired resistance may be a problem

Aerobic gram-positive microorganisms Staphylococci (coagulase negative), Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumoniae.

Aerobic gram-negative microorganisms Acinetobacter baumannii, Citrobacter freundii, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Neisseria gonorrhoeae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia.

Microorganisms with natural resistance to the drug

Aerobic gram-positive microorganisms Enterococci, Listeria monocytogenes, Nocardia, Staphylococci (methicillin-resistant).

Anaerobic microorganisms Bacteroides spp., Clostridium difficile.

Therapeutic doses of ofloxacin have no pharmacological effect on the somatic or autonomic nervous system.

Pharmacokinetics.

After oral administration, ofloxacin is almost completely absorbed. Maximum serum concentration after a single oral dose of 200 mg is 2.5–3 µg/mL and is reached within 1 hour. The serum half-life is 6–7 hours and is linear. The volume of distribution is 120 liters. With repeated administration, the drug concentration in serum does not significantly increase (accumulation ratio is approximately 1.5). Concentrations of ofloxacin in urine and at the site of urinary tract infections exceed serum levels by 5–100 times. Ofloxacin is primarily excreted unchanged in urine. Urinary clearance decreases in renal insufficiency.

Clinical characteristics.

Indications.

The drug Ofloxacin is indicated in adults for the treatment of the following bacterial infections:

• acute pyelonephritis and complicated urinary tract infections;
• bacterial prostatitis, epididymo-orchitis;
• salmonellosis;
• pelvic inflammatory disease in combination with other antibacterial agents;
• urosepsis.

For the following indications, ofloxacin should be used only when the use of other antibacterial agents, which are usually recommended for the treatment of these infections, is considered inappropriate:

• bone and joint infections;
• complicated skin and soft tissue infections;
• acute bacterial sinusitis;
• exacerbation of chronic obstructive pulmonary disease, including bronchitis;
• community-acquired pneumonia.

Ofloxacin is not effective against Treponema pallidum.

Official recommendations on the appropriate use of antibacterial agents and local pathogen susceptibility should be taken into account.

Contraindications.

Ofloxacin must not be administered:

• to patients with hypersensitivity to ofloxacin, other quinolones, or any of the excipients;
• to patients with epilepsy or with a lowered seizure threshold of the central nervous system (CNS);
• to patients with a history of tendinitis associated with the use of quinolones;
• to children or adolescents under 18 years of age;*
• during pregnancy;*
• during breastfeeding;*
• to patients with glucose-6-phosphate dehydrogenase deficiency (which may predispose to hemolytic reactions when treated with quinolones).

*Experimental use of the drug in animals indicates that a negative effect on the joint cartilage of growing organisms cannot be completely ruled out.

Interaction with other medicinal products and other forms of interaction.

Antihypertensive agents, barbiturates

If ofloxacin is administered concomitantly with medicinal products having a potential antihypertensive effect, a sudden drop in blood pressure may occur. Therefore, in such cases and in patients receiving concomitant barbiturate anesthetics, monitoring of cardiovascular function is recommended.

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

No pharmacokinetic interactions between ofloxacin and theophylline have been observed. However, a significant reduction in the seizure threshold may occur when quinolones are used concomitantly with theophylline, NSAIDs, or other agents that reduce the seizure threshold.

If seizures occur, treatment with ofloxacin should be discontinued.

Medicinal products known to prolong the QT interval

Ofloxacin, like other quinolones, should be used with caution in patients receiving medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Prolongation of bleeding time has been reported during concomitant administration of ofloxacin and anticoagulants.

Vitamin K antagonists

Increased coagulation test parameters (prothrombin time/international normalized ratio (INR)) and/or bleeding, which may be severe, have been reported in patients taking ofloxacin together with vitamin K antagonists (e.g., warfarin). In patients receiving vitamin K antagonists, coagulation test parameters should be monitored due to the potential enhancement of the effect of coumarin derivatives.

Glibenclamide

Ofloxacin may cause a slight increase in serum glibenclamide concentrations when used concomitantly; careful monitoring of patients receiving this combination is recommended.

Probenecid, cimetidine, furosemide, methotrexate

Probenecid reduces the total clearance of ofloxacin by 24% and increases the AUC by 16%. The likely mechanism is competition or inhibition of active transport during renal tubular excretion. Caution should be exercised when administering ofloxacin concomitantly with drugs affecting renal tubular secretion, such as probenecid, cimetidine, furosemide, and methotrexate.

Special precautions for use.

The use of ofloxacin should be avoided in patients who have previously experienced serious adverse reactions to quinolones or fluoroquinolones. Treatment with ofloxacin in these patients should be initiated only if no alternative treatment options are available and after careful assessment of benefit/risk.

Prolonged, disabling and potentially irreversible serious adverse reactions

Very rarely, in patients receiving quinolones and fluoroquinolones, regardless of age and existing risk factors, prolonged (lasting for months or years), disabling and potentially irreversible serious adverse reactions affecting various systems of the body, and sometimes several systems simultaneously (including musculoskeletal, nervous, psychiatric, and sensory organs), have been reported. The drug should be discontinued immediately upon the first signs or symptoms of any serious adverse reaction, and medical advice should be sought.

Methicillin-resistant Staphylococcus aureus (MRSA)

MRSA is very likely to be resistant to fluoroquinolones, including ofloxacin. Therefore, ofloxacin is not recommended for the treatment of known or suspected MRSA infections, except when laboratory results have confirmed microbial susceptibility to ofloxacin (and when usually recommended antibacterial agents for MRSA infections are considered inappropriate).

Escherichia coli

Resistance of E. coli, the most common pathogen causing urinary tract infections, to fluoroquinolones varies across all European Union countries. When using ofloxacin, local prevalence of E. coli resistance to fluoroquinolones should be taken into account.

Neisseria gonorrhoeae

Due to increasing resistance of N. gonorrhoeae, ofloxacin should not be used for empirical treatment of 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 within 3 days of treatment, the therapy should be re-evaluated.

Pelvic inflammatory disease

In pelvic inflammatory disease, ofloxacin should be used only in combination with anaerobic coverage.

P. aeruginosa

Hospital-acquired and other serious infections caused by P. aeruginosa may require combination therapy. In specific infections caused by P. aeruginosa, resistance levels should be tested to ensure treatment efficacy.

Streptococci

Ofloxacin is not indicated for the treatment of acute tonsillitis caused by β-hemolytic streptococci.

Resistance risk

For certain bacterial species, resistance prevalence may vary depending on geographical region and over time; therefore, obtaining local resistance data is advisable. Microbiological diagnosis, including pathogen isolation and susceptibility testing, should be established, especially when treating severe infections or in cases of lack of response to therapy.

Bone and joint infections

In bone and joint infections, the need for combination therapy with other antimicrobial agents should be considered.

Serious bullous reactions

Cases of serious bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported during ofloxacin therapy. Patients should be advised to contact their physician immediately before continuing treatment if skin and/or mucosal reactions occur.

Hypersensitivity and allergic reactions

Allergic and hypersensitivity reactions have been reported after the first 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., shock management, including antihistamines, corticosteroids, sympathomimetics, and, if necessary, respiratory support).

Clostridium difficile-associated disease

Diarrhea occurring during or after ofloxacin treatment (even several weeks after therapy) — particularly if severe, prolonged, and/or accompanied by bleeding — may be a symptom of pseudomembranous colitis (Clostridium difficile-associated disease). The severity of Clostridium difficile-associated diarrhea may range from mild to life-threatening. The most severe form of this condition is pseudomembranous colitis. Therefore, this diagnosis should be considered in patients with severe diarrhea during or after ofloxacin therapy. 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 predisposed to seizures

Quinolones may lower the seizure threshold and provoke seizures. Ofloxacin is contraindicated in patients with a history of epilepsy. As with other quinolones, ofloxacin should be used with extreme caution in patients predisposed to seizures, such as those with CNS disorders or those concurrently taking phenylbutazone and similar NSAIDs, or drugs that lower the central nervous system seizure threshold (e.g., theophylline).

If seizures occur, treatment should be discontinued and appropriate standard measures initiated (e.g., maintaining airway patency and administration of anticonvulsants such as diazepam or barbiturates).

Tendinitis and tendon rupture

Tendinitis and tendon rupture (not limited to the Achilles tendon), sometimes bilateral, may occur as early as 48 hours after initiation of 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 renal impairment, organ transplant recipients, and patients receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

If signs of tendinitis (e.g., painful swelling, inflammation) occur, ofloxacin therapy should be discontinued and alternative treatment options considered. The affected limb should be appropriately managed (e.g., immobilized). Corticosteroids should not be used if signs of tendinopathy appear.

Patients with renal impairment

Ofloxacin is primarily eliminated via the kidneys; therefore, dose adjustment of ofloxacin is required in patients with renal impairment, and renal function should be monitored during therapy.

Patients with history of psychiatric 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 therapeutic measures initiated. 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 signs or symptoms of liver disease occur, such as anorexia, jaundice, dark 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 (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 classes are used concomitantly.

Myasthenia gravis

Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. The use of fluoroquinolones in patients with myasthenia gravis during the post-marketing period has been associated with serious adverse reactions, including fatalities and the need for respiratory support. Ofloxacin is not recommended for use in patients with a history of myasthenia gravis.

Photosensitivity warning

Cases of photosensitivity have been reported during ofloxacin therapy. Patients are advised to avoid exposure to intense sunlight and artificial ultraviolet radiation (e.g., mercury-vapor lamps, tanning beds) during treatment and for 48 hours after discontinuation of ofloxacin to prevent photosensitivity.

Superinfection

As with other antibiotics, prolonged use of ofloxacin may lead to overgrowth of resistant microorganisms; therefore, the patient's condition should be monitored regularly. If secondary infection occurs during treatment, appropriate measures should be taken.

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 known risk factors for QT prolongation, including:

• congenital long QT syndrome;
• concomitant use of drugs known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
• cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia);
• elderly patients and women may be more sensitive to QT-prolonging drugs. Therefore, caution is advised when using fluoroquinolones, including ofloxacin, in these patient groups.

Dysglycemia

As with other quinolones, disturbances in blood glucose levels, including both hypoglycemia and hyperglycemia, have been reported, usually in diabetic patients receiving concomitant hypoglycemic agents (e.g., glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Close monitoring of blood glucose levels is recommended in diabetic patients.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hyposthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients receiving ofloxacin should be warned to inform their physician before continuing treatment if they experience neuropathic symptoms such as pain, burning, tingling, numbness, or weakness, to prevent the development of potentially irreversible conditions.

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 medication.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or diagnosed glucose-6-phosphate dehydrogenase deficiency may be susceptible to hemolytic reactions during treatment with quinolones. Therefore, ofloxacin should be administered with caution in such patients. If ofloxacin must be used in these patients, monitoring for possible hemolysis should be performed.

Visual disturbances

If visual disturbances or any ocular symptoms occur, patients should seek immediate ophthalmological evaluation.

Effect on laboratory test results

Patients receiving ofloxacin may have false-positive results in urine tests for opiates or porphyrins. Confirmation of positive opiate or porphyrin test results may require more specific testing methods.

Aortic aneurysm or dissection, valvular regurgitation/insufficiency

Epidemiological studies suggest an increased risk of aortic aneurysm and dissection, particularly in elderly individuals, as well as an increased risk of aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and valvular 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 treatments in patients with a family history of aneurysm or congenital heart valve defects, patients with diagnosed aortic aneurysm or aortic dissection, patients with heart valve disease, and in the presence of other risk factors, including:

• risk factors for aortic aneurysm, aortic dissection, or valvular 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, giant cell arteritis, atherosclerosis, Sjögren’s syndrome;
• risk factors for valvular regurgitation/insufficiency: infective endocarditis.

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

If sudden abdominal, chest, or back pain occurs, patients should seek immediate medical attention.

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

Other considerations

Patients who have previously experienced serious adverse reactions (e.g., severe neurological reactions) to other quinolones have an increased risk of developing similar reactions during ofloxacin therapy.

If severe hypotension occurs during infusion, the infusion should be stopped immediately.

This medicinal product contains 15.427 mmol (or 354.7 mg) of sodium per 100 ml. Caution should be exercised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy

Limited human data suggest that fluoroquinolone therapy during the first trimester of pregnancy is not associated with an increased risk of major congenital malformations or other adverse pregnancy outcomes. Animal studies have shown cartilage damage in immature animals, but no teratogenic effects. Therefore, ofloxacin is contraindicated during pregnancy.

Breastfeeding

Ofloxacin passes into breast milk in small amounts. Due to the potential risk of arthropathy and other serious toxic effects in infants, breastfeeding should be discontinued during ofloxacin therapy.

Ability to affect reaction speed when driving or operating machinery.

Some adverse reactions (e.g., dizziness/vertigo, somnolence, visual disturbances) may impair a patient's ability to concentrate and reduce reaction speed, thereby posing a risk in situations where these abilities are particularly important (e.g., driving vehicles, operating machinery, working at heights). Patients should be aware of how they react to the drug before driving or operating machinery. These effects may be enhanced by alcohol consumption.

Method of administration and dosage.

The dosage, route of administration, and duration of treatment are determined by the type and severity of the infection.

Dosage for patients with normal renal function

Indications	Daily dosage (depending on severity)	Duration of treatment (depending on severity)
Complicated urinary tract infections	200 mg twice daily (may be increased to 400 mg twice daily)	7–21 days
Acute pyelonephritis	200 mg twice daily (may be increased to 400 mg twice daily)	7–10 days (may be extended to 14 days)
Bacterial prostatitis	200 mg twice daily (may be increased to 400 mg twice daily)	2–4 weeks*, 4–8 weeks*
Epididymo-orchitis	200 mg twice daily (may be increased to 400 mg twice daily)	14 days
pelvic inflammatory disease	400 mg twice daily	14 days
Urosepsis	200 mg twice daily	See general information in the section "Duration of treatment"
Bone and joint infections	200 mg twice daily	for 3–4 days (may be prolonged in individual cases)
Complicated skin and soft tissue infections	200 mg twice daily	See general information in the section "Duration of treatment"
Acute bacterial sinusitis	200 mg twice daily	See general information in the section "Duration of treatment"
Acute exacerbation of COPD, including bronchitis	200 mg twice daily	See general information in the section "Duration of treatment"
Community-acquired pneumonia	200 mg twice daily	See general information in the section "Duration of treatment"

*in prostatitis, treatment duration may be considered for extension after careful re-evaluation of the patient.

For completion of treatment in patients who have shown improvement during initial intravenous ofloxacin therapy, oral ofloxacin may be used.

In individual cases, when treating severe infections caused by pathogens with varying sensitivity (e.g., respiratory tract or bone infections) or in case of inadequate patient response to treatment, it may be necessary to increase the dose. In such cases, the dose may be increased to 400 mg twice daily. The same applies to infections with accompanying cofactors.

It is important to maintain approximately equal dosing intervals.

Geriatric patients

Dosage adjustment is not required for geriatric patients, except when taking into account possible renal function impairment.

Renal function impairment

In patients with moderate and severe renal function impairment, as determined by creatinine clearance or serum creatinine levels, the following dosage adjustments are recommended:

The dose should be reduced as follows:

Creatinine clearance	Single dose*	Interval
50–20 ml/min	100–200 mg	24 hours
≤ 20 ml/min ** or hemodialysis or peritoneal dialysis	100 mg or 200 mg	24 hours 48 hours

* Depending on the indication or dosing interval.

** In patients with severe renal function impairment and in patients undergoing dialysis, serum ofloxacin concentrations should be monitored.

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

Men:

or

Women:

However, in individual cases (see above), it may be necessary to increase the dose stated above.

Hepatic impairment

In patients with severe hepatic dysfunction (e.g., cirrhosis with ascites), ofloxacin excretion may be reduced. In such cases, exceeding the maximum daily dose of ofloxacin of 400 mg is not recommended.

Method of administration

Ofloxacin is intended for slow intravenous infusion. Before use, the cap should be removed and the stopper surface disinfected with a suitable disinfectant.

The infusion time for 200 mg of the drug should be no less than 30 minutes. This is particularly important when ofloxacin is administered concomitantly with medicinal products that may lead to a reduction in arterial pressure or with barbiturate-containing anesthetics.

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

Ofloxacin may only be mixed with solutions whose compatibility has been confirmed.

Ofloxacin should not be mixed with heparin and mannitol.

Ofloxacin should only be administered as a freshly prepared solution.

If the patient's condition improves, the intravenous form of ofloxacin may be switched to the oral form at the same dose.

Duration of treatment

The duration of treatment depends on the pathogen response and clinical presentation. Typically, treatment should continue for at least 2–3 days after defervescence and resolution of other symptoms.

For acute infections, the duration of treatment is usually 7–10 days.

The duration of treatment should not exceed 2 months.

Children.

The drug is contraindicated in children and adolescents (under 18 years of age).

Overdose.

Signs of intoxication

The most important signs of acute overdose include, but are not limited to, symptoms related to the CNS (confusion, dizziness, lethargy, seizures), QT interval prolongation, and gastrointestinal disturbances such as nausea or mucosal erosion.

In the post-marketing period, CNS-related adverse events have been observed, including confusion, seizures, hallucinations, and tremor.

Treatment of intoxication

In case of overdose, symptomatic treatment should be initiated. Due to the potential for QT interval prolongation, ECG monitoring should be performed. Monitoring and stabilization of vital functions of other organs in the intensive care unit may be required.

If seizures occur, immediate treatment with anticonvulsant agents is recommended. Elimination of ofloxacin in overdose may be accelerated by forced diuresis. A portion of ofloxacin may be removed from the body by hemodialysis. Peritoneal dialysis and continuous ambulatory peritoneal dialysis are ineffective in removing ofloxacin from the body. There is no specific antidote.

Side effects

The frequency of adverse reactions is defined according to the following conventional classification: common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from available data).

Infectious and parasitic diseases. Uncommon: fungal infections, pathogen resistance.

Blood and lymphatic system disorders. Very rare: anaemia, haemolytic anaemia, leucopenia, eosinophilia, thrombocytopenia, pancytopenia. Frequency not known: agranulocytosis, bone marrow dysfunction.

Immune system disorders. Rare: anaphylactic reactions, anaphylactoid reactions, angioneurotic oedema. Very rare: anaphylactic shock, anaphylactoid shock.

Metabolism and nutrition disorders. Rare: anorexia. Frequency not known: increased serum cholesterol levels, increased serum triglyceride levels, hyperglycaemia, hypoglycaemia in patients with diabetes mellitus receiving antidiabetic medicinal products, hypoglycaemic coma.

Nervous system disorders*. Uncommon: psychomotor agitation, sleep disorders, insomnia. Rare: psychotic disorders (e.g., hallucinations), restlessness, confusion, nightmares, depression, delirium. Frequency not known: psychotic disorders and depression with self-harming 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, seizures, extrapyramidal symptoms or other disturbances of muscular coordination. Frequency not known: tremor, dyskinesia, ageusia, loss of consciousness.

Eye disorders*. Uncommon: eye irritation, burning eyes, conjunctivitis. Rare: visual disturbances (e.g., blurred vision, diplopia, chromatic vision disturbances). Frequency not known: uveitis.

Ear and labyrinth disorders*. Uncommon: vertigo. Very rare: tinnitus, hearing loss. Frequency not known: worsening of hearing.

Cardiac disorders**. Uncommon: palpitations. 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, arterial hypertension. Frequency not known: severe arterial hypotension or collapse with loss of consciousness.

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 (ALT, AST, LDH, GGT and/or alkaline phosphatase), increased blood bilirubin levels. Very rare: cholestatic jaundice. Frequency not known: hepatitis, which may sometimes be severe; severe liver injury, including cases of acute liver failure (sometimes fatal), has been reported during ofloxacin therapy, primarily in patients with severe underlying liver disease.

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, vasculitic purpura, 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 of the Achilles tendon), which may be bilateral and occur within 48 hours of initiating treatment. Frequency not known: rhabdomyolysis and/or myopathy, muscle weakness, muscle tears, muscle ruptures, ligament ruptures, 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 reactions (pain, redness). Frequency not known: general weakness, fever, pain (including back, chest and limb pain).

* In very rare cases, serious, long-lasting (months or years), disabling and potentially irreversible adverse reactions have been reported in patients receiving quinolones and fluoroquinolones, regardless of age and presence of risk factors, affecting various systems and sensory organs, sometimes multiple simultaneously (including reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy-related paraesthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, taste and smell disturbances).

** Cases of aneurysm or dissection of the aorta, sometimes complicated by rupture (including fatal cases), and cases of regurgitation/insufficiency of any heart valve have been reported in patients treated with fluoroquinolones (see section "Special warnings and precautions for use").

Shelf life. 4 years.

Storage conditions. Store at temperatures not exceeding 25 °C, protected from light and out of reach of children.

Incompatibilities.

Other solutions or medicinal products should not be added to the vial containing the medicinal product.

Ofloxacin is incompatible with heparin and mannitol.

Ofloxacin is compatible with the following solutions and medicinal products: 0.9% sodium chloride solution, 5% glucose solution, Ringer's solution.

Packaging. 100 ml or 200 ml in a vial, 1 vial in a carton.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Infuziya".

Manufacturer's address and location of business activity.

Ukraine, 21034, Vinnytsia, Voloshkova St., 55

or Ukraine, 23219, Vinnytsia region, Vinnytsia district, village Vinnytski Khutory, Nemirovskе Highway, 84A.