Levofloxacin

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

Composition:

active substance: levofloxacin;

1 ml of infusion solution contains: levofloxacin hemihydrate equivalent to levofloxacin – 5 mg;

excipients: sodium chloride, disodium edetate, hydrochloric acid, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear solution of yellowish-green color.

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

ATC code J01MA12.

Pharmacological properties.

Pharmacodynamics.

Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone group, the S-enantiomer of the racemic mixture of the drug ofloxacin.

Mechanism of action. As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA gyrase and topoisomerase IV complex.

Pharmacokinetic/pharmacodynamic relationship. The degree of antibacterial activity of levofloxacin depends on the ratio of maximum serum concentration (Cmax) or area under the concentration-time curve (AUC) to minimum inhibitory (suppressive) concentration (MIC).

Mechanism of resistance. The primary mechanism of resistance is due to mutations in the gyr-A genes. In vitro, cross-resistance exists between levofloxacin and other fluoroquinolones.

Due to its mechanism of action, cross-resistance between levofloxacin and other classes of antibacterial agents is generally not observed.

Breakpoints

The recommended breakpoints of levofloxacin MIC values established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which distinguish susceptible microorganisms from moderately susceptible (moderately resistant) organisms and intermediate susceptible from resistant organisms, are shown in Table 1 of MIC testing (mg/L).

Clinical breakpoints for levofloxacin (version 10.0, 01-01-2020).

Table 1

1 only uncomplicated urinary tract infections

2 Susceptibility can be inferred based on sensitivity to ciprofloxacin

Resistance prevalence may vary geographically and over time for selected species. Local information on resistance should be sought, especially when treating severe infections. Advice from a specialist should be sought when local resistance prevalence is such that the utility of the drug is at least questionable for certain types of infections.

*Methicillin-resistant S. aureus is highly likely to exhibit co-resistance to fluoroquinolones, including levofloxacin.

Pharmacokinetics.

Steady state is achieved within 48 hours with a dosing regimen of 500 mg once or twice daily.

The mean volume of distribution of levofloxacin is approximately 100 L after single and repeated 500 mg doses, indicating extensive distribution into body tissues. Tissue and fluid penetration.

Levofloxacin penetrates well into bronchial mucosa, epithelial lining fluid, alveolar macrophages, lung tissue, skin (vesicle content), prostatic tissue, and urine. However, penetration into cerebrospinal fluid is poor.

Metabolism. Levofloxacin undergoes minimal metabolism, with metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the total drug excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.

Elimination. Following oral and intravenous administration, levofloxacin is eliminated from plasma relatively slowly (elimination half-life is 6–8 hours), primarily via the kidneys (over 85% of the administered dose).

The mean total systemic clearance of levofloxacin after a single 500 mg dose was 175 ± 29.2 mL/min.

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration, indicating that these routes (oral and intravenous) are interchangeable.

Linearity.

Levofloxacin exhibits linear pharmacokinetics over the range of 50–1000 mg.

Patients with renal impairment.

Renal impairment affects the pharmacokinetics of levofloxacin. With decreased renal function, renal elimination and clearance are reduced, and elimination half-life is prolonged, as shown in Table 1.

Table 1.

Geriatric Patients

There are no significant differences in the pharmacokinetics of levofloxacin in younger and elderly patients, except for differences related to creatinine clearance.

Gender Differences

Separate analysis of male and female patients demonstrated minor differences in the pharmacokinetics of levofloxacin depending on gender. There is no evidence that these gender differences are clinically significant.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to the drug:

• Community-acquired pneumonia*;
• Complicated skin and soft tissue infections*;
• Acute pyelonephritis and complicated urinary tract infections;
• Chronic bacterial prostatitis;
• Pulmonary form of anthrax: post-exposure prophylaxis and treatment.

*For the above-mentioned infectious diseases, levofloxacin should be prescribed only when other antibacterial agents, primarily used for initial treatment of these infections, are insufficiently effective.

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

Contraindications.

Hypersensitivity to any component of the drug, to levofloxacin, or to other quinolones. Epilepsy, tendon-related adverse reactions following prior quinolone therapy. Pregnancy or breastfeeding. Pediatric age (under 18 years).

Interaction with other medicinal products and other forms of interactions.

Theophylline, fenbufen, or similar nonsteroidal anti-inflammatory drugs (NSAIDs). Levofloxacin showed no pharmacokinetic interactions with theophylline (a marker substrate for the CYP1A2 enzyme), indicating that levofloxacin is not a CYP1A2 inhibitor. However, a marked reduction in the cerebral seizure threshold may occur when quinolones are administered concomitantly with theophylline, NSAIDs, or other agents that lower the seizure threshold. Levofloxacin concentrations were approximately 13% higher in the presence of fenbufen compared to administration of levofloxacin alone.

Probenecid and cimetidine. Both exhibit statistically significant effects on levofloxacin elimination; renal clearance of levofloxacin was reduced when administered with cimetidine (by 24%) and probenecid (by 34%). This is because both agents can block tubular secretion of levofloxacin. However, at the doses tested in the study, it is unlikely that statistically significant kinetic differences would have clinical relevance. Levofloxacin should be administered with caution concomitantly with drugs affecting renal tubular secretion (probenecid and cimetidine), especially in patients with impaired renal function.

Cyclosporine. The elimination half-life of cyclosporine increases by 33% when administered concomitantly with levofloxacin.

Vitamin K antagonists. In patients receiving levofloxacin concomitantly with vitamin K antagonists (e.g., warfarin), prolonged prothrombin time (increased international normalized ratio/decreased Quick's prothrombin index) and/or even bleeding events have been reported. Such bleeding may be severe. Therefore, coagulation parameters should be monitored in patients undergoing treatment with vitamin K antagonists (see section "Special precautions for use").

Medicinal products that prolong the QT interval. Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products capable of prolonging the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants and macrolides, antipsychotics).

The pharmacokinetics of levofloxacin were not altered when coadministered with calcium carbonate, digoxin, glyburide, ranitidine, warfarin.

No effect of levofloxacin on theophylline pharmacokinetics (a substrate of the CYP1A2 enzyme) was observed, confirming that levofloxacin is not a CYP1A2 inhibitor.

Concomitant use of levofloxacin with alcohol is not recommended.

Concomitant use with glucocorticoids increases the risk of tendon rupture.

Special precautions for use.

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

Patients with pronounced cerebral atherosclerosis or cerebrovascular disorders should exercise caution when using the drug.

An aneurysm and dissection of the aorta and regurgitation/insufficiency of heart valves

Epidemiological data suggest an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and regurgitation of aortic and mitral valves, following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any heart 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 an existing diagnosis of aneurysm and/or dissection of the aorta, or heart valve disease, or in the presence of other risk factors or predisposing conditions:

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

If sudden abdominal, chest, or back pain occurs, patients should immediately seek medical attention at an emergency department.

Patients should be advised to seek immediate medical help if they experience acute shortness of breath, a new episode of palpitations, or develop abdominal or lower limb edema.

Renal impairment.

Levofloxacin is primarily excreted via the kidneys; therefore, dose adjustment is required in patients with renal impairment.

Renal and hepatic function should be monitored throughout the treatment course. If adverse effects occur, particularly those affecting the central nervous system (CNS) or allergic reactions, which may occur after the first dose, levofloxacin should be discontinued.

Patients with seizure predisposition.

Quinolones may lower the seizure threshold and provoke seizures.

Levofloxacin is contraindicated in patients with a history of epilepsy. As with other quinolones, levofloxacin should be used with extreme caution in patients predisposed to seizures or those concurrently taking medicinal products that lower the cerebral seizure threshold, such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). If seizures occur, treatment with levofloxacin should be discontinued.

Concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs or agents that lower the cerebral seizure threshold, such as theophylline, also requires caution. If seizures occur, levofloxacin treatment should be discontinued.

Photosensitivity reactions.

Photosensitivity reactions have been reported during treatment with levofloxacin.

To prevent photosensitivity reactions, patients taking levofloxacin should avoid exposure to sunlight and UV radiation (UV lamps, tanning beds) due to possible photosensitization during or within 48 hours after discontinuation of levofloxacin.

Resistance.

For methicillin-resistant Staphylococcus aureus (MRSA), there is a very high likelihood of co-resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections where MRSA is known or suspected, except when laboratory testing confirms susceptibility of the pathogen to levofloxacin.

Escherichia coli resistant to levofloxacin may be a common cause of urinary tract infections, which should be considered when prescribing levofloxacin for urinary tract infections. Prescribing physicians are advised to consider local prevalence of E. coli resistance to fluoroquinolones.

Pulmonary form of anthrax.

Clinical practice is based on in vitro susceptibility studies of Bacillus anthracis, experimental animal data, and limited human data. Physicians should refer to established national and/or international guidelines for the treatment of anthrax.

Infusion duration

The recommended infusion rate must be observed: at least 30 minutes for a 250 mg dose and 60 minutes for a 500 mg dose. With ofloxacin, tachycardia and transient increases in blood pressure may occur during infusion. In rare cases, this may lead to a sudden drop in blood pressure or circulatory collapse. If a marked decrease in blood pressure occurs during levofloxacin (*l-*isomer of ofloxacin) infusion, the infusion should be immediately stopped.

Tendinitis and tendon rupture.

Tendinitis may occur in isolated cases. Tendon inflammation and rupture (particularly, but not limited to, the Achilles tendon), sometimes bilateral, may occur within the first 48 hours of initiating quinolone or fluoroquinolone therapy, and cases have also been reported several months after discontinuation of the drug. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, patients who have undergone solid organ transplantation, patients receiving a daily dose of 1000 mg levofloxacin, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of corticosteroids should be avoided.

At the first signs of tendinitis (e.g., painful swelling, inflammation), treatment with levofloxacin should be immediately discontinued and alternative treatment options considered. Affected limbs should be appropriately managed (e.g., immobilization). Corticosteroids are not recommended in cases of tendonopathy.

Myoclonus.

Cases of myoclonus have been reported in patients receiving levofloxacin (see section "Adverse reactions"). The risk of myoclonus is increased in elderly patients and in patients with renal impairment if the levofloxacin dose is not adjusted according to creatinine clearance. Levofloxacin should be immediately discontinued at the first sign of myoclonus, and appropriate treatment initiated.

Clostridium difficile-associated disease.

Diarrhea, especially severe, persistent, and/or bloody, during or after treatment may indicate Clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, treatment with the drug should be immediately discontinued and symptomatic and specific treatment initiated without delay (e.g., vancomycin). In this clinical situation, drugs that inhibit intestinal peristalsis are contraindicated.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Patients with latent or manifest G6PD deficiency may be prone to hemolytic reactions when treated with quinolone antibacterial agents. Therefore, if levofloxacin must be used in such patients, monitoring for possible hemolysis is recommended.

Exacerbation of myasthenia gravis.

Fluoroquinolones, including levofloxacin, have neuromuscular blocking effects and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including respiratory failure requiring respiratory support and fatal outcomes, have been associated with fluoroquinolone use in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a known history of myasthenia gravis.

Psychotic reactions.

Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. Very rarely, these have led to suicidal thoughts and self-harming behavior, sometimes even after a single dose of levofloxacin. If such reactions occur, levofloxacin should be discontinued and appropriate measures taken. Caution is recommended when prescribing levofloxacin to patients with a history of psychotic disorders or psychiatric illness.

Severe skin adverse reactions.

Severe skin reactions have been reported with levofloxacin, including toxic epidermal necrolysis (TEN; also known as Lyell’s syndrome), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be life-threatening or fatal (see section "Adverse reactions").

Patients should be informed about the signs and symptoms of severe skin reactions before starting treatment and closely monitored. If signs or symptoms suggestive of these reactions appear, levofloxacin should be immediately discontinued and alternative treatment considered.

If a serious reaction such as SJS, TEN, or DRESS occurs with levofloxacin, levofloxacin treatment should not be resumed in that patient at any time.

Patients taking vitamin K antagonists.

Patients receiving vitamin K antagonists should have coagulation parameters monitored during concomitant use of levofloxacin and vitamin K antagonists (e.g., warfarin) due to the potential risk of increased coagulation parameters (prothrombin time/INR) and/or bleeding.

Hypersensitivity reactions.

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (e.g., angioedema, up to anaphylactic shock), even after the first dose. In such cases, patients should discontinue treatment immediately and seek medical attention.

Dysglycemia.

As with all quinolones, disturbances in blood glucose levels (including hyper- and hypoglycemia) have been reported with levofloxacin, typically in diabetic patients receiving concomitant oral antidiabetic agents (e.g., glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Close monitoring of blood glucose levels is recommended in patients with diabetes mellitus.

QT interval prolongation.

Fluoroquinolones, including levofloxacin, should be used with caution in patients with known risk factors for QT interval prolongation, such as:

• congenital or acquired long QT syndrome;
• concomitant use of medicinal products that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
• advanced age;
• heart disease (e.g., heart failure, myocardial infarction, bradycardia).

Elderly patients and women are more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used cautiously in these patient groups.

Peripheral neuropathy.

Cases of sensory or sensorimotor peripheral neuropathy leading to paresthesia, hypoesthesia, dysesthesia, or weakness have been reported in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be discontinued if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, to prevent irreversible damage.

Opioids.

In patients receiving levofloxacin, urine testing for opioids may yield false-positive results. Confirmation of positive opioid results using more specific methods may be necessary.

Levofloxacin inhibits the growth of Mycobacterium tuberculosis, potentially leading to false-negative results in bacteriological testing in patients with tuberculosis.

Hepatobiliary disorders. Cases of necrotic hepatitis, up to hepatic failure, sometimes fatal, have been reported with levofloxacin, primarily in patients with severe underlying conditions such as sepsis (see section "Adverse reactions"). Patients should be advised to discontinue treatment and consult a physician if symptoms of liver disease such as anorexia, jaundice, dark urine, pruritus, or abdominal pain occur.

Acute pancreatitis.

Acute pancreatitis may occur in patients taking levofloxacin. Patients should be informed about the typical symptoms of acute pancreatitis. Patients experiencing nausea, malaise, abdominal discomfort, severe abdominal pain, or vomiting should be immediately evaluated by a physician. Levofloxacin should be discontinued if acute pancreatitis is suspected and not restarted if confirmed. Caution should be exercised in patients with a history of pancreatitis (see section "Adverse reactions").

Blood disorders.

Bone marrow dysfunction, including leukopenia, neutropenia, pancytopenia, hemolytic anemia, thrombocytopenia, aplastic anemia, or agranulocytosis, may occur during treatment with levofloxacin (see section "Adverse reactions"). If any of these disorders are suspected, blood test results should be monitored. If abnormal results are obtained, discontinuation of levofloxacin treatment should be considered.

Long-term, disabling, and potentially irreversible serious adverse reactions.

In very rare cases, patients receiving quinolones and fluoroquinolones, regardless of age or risk factors, have reported long-term (lasting months or years), disabling, and potentially irreversible adverse reactions affecting various systems, sometimes multiple systems simultaneously (e.g., musculoskeletal, nervous, psychological, and sensory organs). The drug should be immediately discontinued at the first sign or symptom of any serious adverse reaction, and medical advice should be sought.

Sodium.

This medicinal product contains 39.1 mmol (900 mg) of sodium per 100 ml of solution. This should be considered by patients on a sodium-controlled diet.

Visual disturbances.

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

Superinfection.

The use of levofloxacin, particularly over a prolonged period, may lead to overgrowth of microorganisms not susceptible to the drug. If superinfection develops during therapy, appropriate measures should be taken.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy or breastfeeding.

Data on the use of levofloxacin in pregnant and breastfeeding women are limited. Animal studies do not indicate direct or indirect harmful effects on reproductive toxicity. However, due to the lack of human studies (and animal experiments indicating a risk of cartilage damage in weight-bearing joints of growing animals by fluoroquinolones), levofloxacin should not be administered to pregnant women or women who are breastfeeding. If pregnancy is diagnosed during treatment, this should be reported to the physician. If use of the drug is necessary during breastfeeding, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

In some patients, the drug may cause headache, dizziness/vertigo, somnolence, insomnia, visual disturbances, confusion, or motor disorders. Therefore, patients should refrain from driving or operating complex machinery requiring high attention and fast psychomotor responses.

Administration and Dosage

Levofloxacin should be administered immediately (within 3 hours) after perforation of the rubber stopper to prevent bacterial contamination. Protection from light during infusion is not required.

The intravenous solution may be stored under room lighting for up to 3 days without protection from light.

The medicinal product is intended for single use only.

The solution must be inspected visually prior to use. Only clear, particle-free solutions should be used.

As with all other medicinal products, any unused portion should be disposed of in accordance with local regulations.

Levofloxacin infusion solution is administered intravenously as a slow infusion once or twice daily. The dosage depends on the type and severity of infection, as well as the susceptibility of the likely causative organism to the drug. Treatment with Levofloxacin may be initiated intravenously and subsequently completed with an oral formulation, provided such a switch is appropriate for the individual patient. Due to the bioequivalence of parenteral and oral dosage forms, the same dose may be used.

Recommended dosage for adults with normal renal function, in whom creatinine clearance is greater than 50 mL/min.

Table 2

Depending on the patient's clinical condition, a switch from initial intravenous administration to oral administration of levofloxacin at the same dosage may be possible after several days (usually from 2 to 4 days).

Since levofloxacin is primarily eliminated via the kidneys, the dose should be reduced in patients with impaired renal function.

Dosage for adult patients with impaired renal function, in whom creatinine clearance is less than 50 ml/min.

Table 3

1 After hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), additional doses are not required.

Dosing in patients with hepatic impairment. Dose adjustment is not necessary, as levofloxacin is minimally metabolized in the liver.

Dosing in elderly patients. If renal function is normal, dose adjustment is not required.

Levofloxacin is administered intravenously by slow infusion. The duration of infusion should be at least 30 minutes for a 250 mg dose or at least 60 minutes for a 500 mg dose.

Depending on the patient's condition, after several days it may be possible to switch from intravenous administration to oral levofloxacin at the same dosage.

The duration of treatment depends on the course of the disease. As with other antibacterial agents, it is recommended to continue treatment for at least 48–72 hours after normalization of body temperature or confirmed microbiological eradication of the causative organism.

Mixing with other infusion solutions

Levofloxacin is compatible with the following infusion solutions:

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

Children.

The use of the drug is contraindicated in children (under 18 years of age), as articular cartilage damage cannot be excluded.

Overdose.

According to toxicity studies in animals or clinical pharmacological studies conducted with doses higher than therapeutic, the most serious signs expected after acute overdose of levofloxacin infusion solution are central nervous system symptoms such as confusion, dizziness, altered consciousness, seizures, myoclonus, hallucinations, tremor, nausea, mucosal erosion, and QT interval prolongation.

Treatment. In cases of overdose, symptomatic treatment should be administered. ECG monitoring is necessary due to the potential for QT interval prolongation. Hemodialysis, including peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD), is not effective in removing levofloxacin from the body. There are no specific antidotes.

Side effects

The side effects listed below are categorized by organ systems and frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), and not known (cannot be estimated based on available data).

Within each group, side effects are listed in order of decreasing frequency.

aAnaphylactic and anaphylactoid reactions may sometimes occur even after administration of the first dose of the drug.

bSkin and mucous membrane reactions may sometimes occur even after administration of the first dose of the drug.

*In very rare cases, in patients receiving quinolones and fluoroquinolones, regardless of the presence of risk factors, prolonged (for months or years), disabling and potentially irreversible serious adverse reactions affecting various, and sometimes several simultaneously, body systems and sensory organs have been reported (including reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, taste and smell disturbances) (see section "Special precautions").

Other adverse effects associated with fluoroquinolone use:

• Porphyria attacks in patients with existing porphyria.

** In patients receiving fluoroquinolones, cases of aneurysms and aortic dissections, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any heart valve have been reported (see section "Special precautions").

Description of selected adverse reactions

Anxiety, suicidal thoughts, panic attacks, neuralgia, and attention disturbances have been reported as potential components of prolonged and disabling adverse reactions induced by fluoroquinolones.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach of children.

Incompatibility.

The drug should not be mixed with heparin or alkaline solutions (e.g., sodium bicarbonate), or with other drugs, except for medicinal products specified in the section "Dosage and administration".

Packaging.

100 ml in a vial, 1 vial in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

" Unique Pharmaceuticals Laboratories" (a division of "J. B. Chemicals and Pharmaceuticals Ltd.").

Manufacturer's address and location of manufacturing site.

Plot No. 4, Phase-IV, G.I.D.C. Industrial Estate, Panoli - 394 116, Bharuch District, India.