Levofloxacin-astrafarm
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEVOFLOXACIN-ASTRAPHARM (LEVOFLOXACIN-ASTRAPHARM)
Composition:
Active substance: levofloxacin;
One tablet contains levofloxacin 250 mg or 500 mg;
Excipients: crospovidone, microcrystalline cellulose, sodium stearyl fumarate, coating "Selacoat™" (hypromellose, polyethylene glycol 6000, titanium dioxide (E 171)).
Pharmaceutical form. Coated tablets.
Main physicochemical properties: oval-shaped, biconvex tablets coated with a white film.
Pharmacotherapeutic group.
Antibacterial agents for systemic use. Fluoroquinolones.
ATC code J01MA12.
Pharmacological Properties
Pharmacodynamics
Levofloxacin-Astrafarm is a broad-spectrum antibiotic from the quinolone group containing the active substance levofloxacin. Like other fluoroquinolones, levofloxacin inhibits bacterial DNA gyrase, thereby disrupting bacterial DNA function. Levofloxacin is active against both Gram-positive and Gram-negative pathogenic microorganisms, including strains resistant to penicillins, cephalosporins, and/or aminoglycosides. The development of resistance may significantly affect local strain susceptibility to the drug; therefore, this information should be taken into account when prescribing the drug, especially in the treatment of severe infections. Levofloxacin has a broad spectrum of activity against microorganisms both in vitro and in vivo: Enterococcus faecalis, methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Viridans group streptococci, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter sakazakii, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Pseudomonas fluorescens, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Morganella morganii, Proteus vulgaris, Providencia rettgeri and stuartii, Serratia marcescens, Clostridium perfringens.
Like other fluoroquinolones, levofloxacin is inactive against spirochetes.
Pharmacokinetics
After oral administration, levofloxacin is rapidly and almost completely absorbed. Peak plasma concentrations are observed within 1 hour after administration. Absolute bioavailability is nearly 100%. Levofloxacin exhibits linear pharmacokinetics within the dose range of 50–600 mg. Food intake slightly affects drug absorption.
Approximately 30–40% of levofloxacin is protein-bound in plasma. Accumulation of levofloxacin following a 500 mg once-daily dose is not clinically significant. There is a minor but predictable accumulation with a dosage of 500 mg twice daily. Steady-state distribution is achieved within 3 days.
Maximum concentrations of levofloxacin in bronchial mucosa and bronchial epithelial lining fluid following an oral dose exceeding 500 mg were 8.3 and 10.8 mg/mL, respectively.
Maximum concentration of levofloxacin in lung tissue following an oral dose above 500 mg was approximately 11.3 mg/mL, reached within 4–6 hours after administration. Concentrations in lung tissue consistently exceeded those in plasma.
Maximum concentration of levofloxacin in blister fluid after administration of 500 mg once or twice daily was 6.7 mg/mL.
Levofloxacin poorly penetrates into cerebrospinal fluid.
After oral administration of 500 mg levofloxacin once daily for 3 days, mean concentrations in prostate tissue were 8.7 mg/g, 8.2 mg/g, and 2 mg/g at 2, 6, and 24 hours, respectively; the mean prostate/plasma concentration ratio was 1.84.
Mean concentrations of levofloxacin 8–12 hours after a single oral dose of 150 mg, 300 mg, or 500 mg were 44 mg/mL, 91 mg/mL, and 200 mg/mL, respectively.
Levofloxacin undergoes minimal metabolism, forming dimethyl-levofloxacin and levofloxacin-N-oxide as metabolites. These metabolites account for less than 5% of the total amount of drug excreted in urine.
After administration, levofloxacin is eliminated from plasma relatively slowly (elimination half-life is 6–8 hours). Elimination occurs primarily via the kidneys (over 85% of the administered dose). There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration.
Clinical characteristics.
Indications.
Levofloxacin-Astrafarm is indicated for the treatment in adults of the following infections caused by levofloxacin-susceptible microorganisms:
- acute bacterial sinusitis;
- acute exacerbation of chronic bronchitis;
- community-acquired pneumonia;
- complicated skin and soft tissue infections;
(when treating the above-mentioned infections, the drug should be used only when other antibacterial agents typically prescribed for initial treatment of these infections cannot be used);
- complicated urinary tract infections (including acute pyelonephritis);
- chronic bacterial prostatitis.
Official recommendations regarding appropriate use of antibacterial agents should be taken into account.
Contraindications.
Hypersensitivity to levofloxacin, other fluoroquinolones, or to any component of the medicinal product.
Epilepsy.
Tendon damage associated with the use of fluoroquinolones.
Paediatric age.
Pregnancy or breastfeeding.
Interaction with other medicinal products and other forms of interaction.
Effect of other medicinal products on levofloxacin
Iron salts, antacids containing magnesium and aluminium, didanosine.
Absorption of levofloxacin is significantly reduced when taken concomitantly with iron salts and antacids containing magnesium or aluminium. Tablets should be taken at least 2 hours after administration of agents containing divalent or trivalent cations, such as iron salts or antacids containing magnesium or aluminium. No interaction has been observed with calcium carbonate.
It is recommended not to use medicinal products containing divalent or trivalent cations, such as iron salts, zinc salts, antacids containing magnesium or aluminium, or didanosine (this applies only to didanosine formulations containing aluminium or magnesium buffering agents) within 2 hours before or after taking levofloxacin tablets (see section "Dosage and method of administration").
Sucralfate
The bioavailability of levofloxacin is significantly reduced when administered concomitantly with sucralfate. If a patient needs to receive both sucralfate and levofloxacin, it is preferable to take sucralfate 2 hours after administration of Levofloxacin-Astrafarm tablets.
Theophylline, fenbufen, or similar non-steroidal anti-inflammatory drugs
No pharmacokinetic interaction between levofloxacin and theophylline has been observed. However, a significant reduction in seizure threshold may occur with concomitant use of quinolones together with theophylline, non-steroidal anti-inflammatory drugs, and other agents that lower the seizure threshold. Levofloxacin concentrations were approximately 13% higher in the presence of fenbufen than when levofloxacin was administered alone.
Probenecid and cimetidine
Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin.
Renal clearance of levofloxacin is reduced by 24% in the presence of cimetidine and by 34% in the presence of probenecid. This is explained by the fact that both agents are capable of blocking tubular secretion of levofloxacin. However, in studies, statistically significant kinetic differences did not have clinical significance. Concomitant use of levofloxacin with medicinal products affecting tubular secretion, such as probenecid and cimetidine, should be approached with caution, especially in patients with renal impairment.
Other medicinal products
Studies have demonstrated that the pharmacokinetics of levofloxacin were not clinically significantly affected by co-administration with the following medicinal products: calcium carbonate, digoxin, glyburide, ranitidine.
Effect of levofloxacin on other medicinal products
Cyclosporine
The elimination half-life of cyclosporine increases by 33% when administered concomitantly with levofloxacin.
Vitamin K antagonists
When used concomitantly with vitamin K antagonists (e.g., warfarin), increased international normalized ratio (INR) and/or bleeding, which may be severe, have been reported. Therefore, coagulation parameters should be monitored in patients receiving vitamin K antagonists concomitantly.
MEDICINAL PRODUCTS THAT PROLONG THE QT INTERVAL
Levofloxacin, like other fluoroquinolones, 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, and macrolides).
Food intake
No clinically significant interaction with food has been observed. Therefore, Levofloxacin-Astrafarm tablets may be taken independently of food intake.
Special precautions for use.
In very severe cases of pneumonia caused by pneumococci, levofloxacin may not provide optimal therapeutic effect.
Hospital-acquired infections caused by P. aeruginosa may require combination therapy.
Methicillin-resistant S. aureus
There is a very high likelihood of cross-resistance to fluoroquinolones, including levofloxacin, in methicillin-resistant S. aureus (MRSA). Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, except when laboratory testing has confirmed susceptibility of the pathogen to levofloxacin (and when use of typically recommended antibacterial agents for MRSA infections is considered impossible).
The most common pathogen in urinary tract infections is E. coli resistant to levofloxacin, which should be taken into account when prescribing levofloxacin to patients with urinary tract diseases.
Tendinitis and tendon rupture
Tendinitis and tendon rupture (particularly of the Achilles tendon), sometimes bilateral, may occur as early as within 48 hours after initiation of treatment with quinolones and fluoroquinolones, and have been reported even several months after discontinuation of treatment in patients who received a daily dose of 1000 mg levofloxacin. The risk of developing tendinitis and tendon rupture is increased in elderly patients (over 60 years of age), patients with impaired renal function, patients with transplanted solid organs, patients receiving a daily dose of 1000 mg levofloxacin, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of corticosteroids should be avoided. The daily dose should be adjusted in elderly patients based on creatinine clearance. Elderly patients prescribed levofloxacin should be closely monitored.
If any signs of tendinitis (e.g., painful swelling, inflammation) occur, treatment with the drug should be discontinued and alternative therapy should be considered. The affected limb should be appropriately managed (e.g., immobilization). Corticosteroids should not be used in the event of signs of tendinopathy.
Myoclonus
Cases of myoclonus have been reported in patients receiving levofloxacin (see section "Adverse reactions"). The risk of developing myoclonus is increased in elderly patients and in patients with renal impairment if the dose of levofloxacin is not adjusted according to creatinine clearance. If myoclonus occurs, levofloxacin should be discontinued immediately and appropriate treatment initiated.
Clostridium difficile-associated diseases
Diarrhea, especially severe, persistent, and/or hemorrhagic, during or after treatment with the drug may be a symptom of a disease caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, the drug should be discontinued immediately, and supportive therapy should be initiated without delay; specific therapy (e.g., oral vancomycin) should be started if necessary. Medicinal products that inhibit intestinal motility are contraindicated in this clinical situation.
Patients predisposed to seizures
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, such as patients with central nervous system disorders, those receiving concomitant therapy with phenylbutazone and similar nonsteroidal anti-inflammatory drugs, or drugs that increase seizure susceptibility (lower the seizure threshold), such as theophylline. If seizures occur, treatment with levofloxacin should be discontinued.
Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with reduced glucose-6-phosphate dehydrogenase activity are prone to hemolytic reactions when treated with quinolone-class antibacterial agents; therefore, levofloxacin should be used with caution in these patients.
Patients with renal impairment
Since levofloxacin is primarily excreted by the kidneys, dose adjustment is required in patients with impaired renal function (renal insufficiency).
Hypersensitivity reactions
Levofloxacin may cause severe hypersensitivity reactions (e.g., angioedema up to anaphylactic shock). In such cases, patients should discontinue treatment immediately and seek medical attention.
Severe skin adverse reactions
Severe skin reactions, including toxic epidermal necrolysis (TEN, also known as Lyell's syndrome), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during treatment with levofloxacin, which may result in fatal outcomes.
Patients should be informed about the signs of severe skin reactions and closely monitored during treatment.
At the first signs of such reactions, levofloxacin should be discontinued immediately and alternative therapy considered. If a patient experiences a serious skin reaction such as toxic epidermal necrolysis (TEN: also known as Lyell's syndrome), Stevens-Johnson syndrome (SJS), or drug reaction with eosinophilia and systemic symptoms (DRESS) while taking levofloxacin, this medicinal product should not be prescribed again in the future.
Disturbances of blood glucose
During treatment with levofloxacin, as with other quinolones, fluctuations in blood glucose levels have been reported, including cases of hyperglycemia and hypoglycemia, particularly in patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (e.g., glibenclamide) or insulin. Cases of hypoglycemic coma have been documented. Close monitoring of blood glucose levels is recommended in patients with diabetes mellitus (see section "Adverse reactions").
Prevention of photosensitization
Although photosensitization is very rare with levofloxacin, to avoid it, patients should not be exposed to strong sunlight or artificial UV radiation (e.g., UV lamps, tanning beds) during treatment with levofloxacin and for 48 hours after discontinuation of levofloxacin.
Patients receiving vitamin K antagonists
Due to the potential for increased INR and/or bleeding in patients taking levofloxacin in combination with a vitamin K antagonist (e.g., warfarin), coagulation test results should be monitored in such cases.
Psychotic reactions
Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. In rare cases, these reactions progressed to suicidal thoughts and self-destructive behavior, sometimes after only a single dose of levofloxacin. If such reactions occur, levofloxacin should be discontinued and appropriate measures taken. Levofloxacin should be used with caution in patients with psychotic disorders or a history of psychiatric illness.
QT interval prolongation
Caution should be exercised when using fluoroquinolones, including levofloxacin, in patients with known risk factors for QT interval prolongation, such as:
- congenital QT prolongation syndrome;
- acquired QT prolongation;
- concomitant use of medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
- uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
- elderly patients and women are more sensitive to drugs that prolong the QT interval;
- heart disease (e.g., heart failure, myocardial infarction, bradycardia).
Blood disorders
Treatment with levofloxacin may lead to bone marrow dysfunction, including leukopenia, neutropenia, pancytopenia, hemolytic anemia, thrombocytopenia, aplastic anemia, or agranulocytosis (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 therapy should be considered.
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. If symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, patients being treated with the drug should be advised to inform their physician to prevent potentially irreversible conditions.
Hepatobiliary disorders
Cases of necrotizing hepatitis, up to life-threatening liver failure, 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 occur, such as anorexia, jaundice, dark urine, pruritus, or abdominal pain.
Laboratory tests
In patients receiving levofloxacin, urine testing for opioids may yield false-positive results. Confirmation of positive opioid test results using specific methods may be necessary.
Levofloxacin inhibits the growth of Mycobacterium tuberculosis, which may result in false-negative bacteriological test results in patients with tuberculosis.
Aortic aneurysm or dissection and cardiac valve regurgitation/insufficiency
Epidemiological studies report 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 cardiac valve have been reported in patients receiving fluoroquinolones (see section "Adverse reactions").
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and consideration of alternative therapeutic options in patients with a positive family history of aneurysm or congenital heart valve defect, or in patients with an existing diagnosis of aneurysm and/or aortic dissection, or heart valve disease, or in the presence of other risk factors or predisposing conditions
- both for aortic aneurysm and dissection and for cardiac valve regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome, vascular type Ehlers-Danlos syndrome or 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 cardiac valve regurgitation/insufficiency (e.g., infective endocarditis). The risk of aortic aneurysm and dissection and their rupture may be increased in patients receiving systemic corticosteroids concomitantly.
In case of sudden abdominal, chest, or back pain, patients should seek immediate medical attention at an emergency department.
Patients should be advised to seek immediate medical help if acute shortness of breath, a new episode of palpitations, or development of abdominal or lower limb edema occurs.
Prolonged, disabling, and potentially irreversible serious adverse reactions
Very rare cases of prolonged (lasting several months or years), disabling, and potentially irreversible serious adverse reactions affecting various body systems (musculoskeletal, nervous system, mental health, sensory organs) have been observed in patients receiving quinolones and fluoroquinolones, regardless of age or presence of risk factors. Patients should be advised to immediately discontinue levofloxacin and consult a physician if the first symptoms of any serious adverse reaction occur.
Myasthenia gravis
Fluoroquinolones, including levofloxacin, block neuromuscular transmission and may provoke muscle weakness in patients with myasthenia gravis. Serious adverse reactions, including fatalities and the need for respiratory support, have been reported in post-marketing experience in patients with myasthenia gravis receiving fluoroquinolones. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.
Visual disorders
If visual disturbances or other ocular effects occur, immediate consultation with an ophthalmologist is required (see sections "Adverse reactions", "Ability to affect reaction speed when driving or operating machinery").
Superinfection
With use of levofloxacin, particularly prolonged use, development of opportunistic infections and overgrowth of resistant microorganisms is possible. Appropriate measures should be taken if secondary infection develops.
Excipients
This medicinal product contains sodium stearyl fumarate. Caution should be exercised when administering to patients on a sodium-controlled diet.
Use during pregnancy or breastfeeding
Due to the lack of human studies and the potential for quinolones to damage the joint cartilage in a growing organism, the drug should not be administered during pregnancy or breastfeeding. If pregnancy occurs during treatment with the drug, this should be reported to the physician.
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; therefore, patients should refrain from driving or operating machinery during treatment.
Dosage and Administration
The medication should be taken 1–2 times daily. The dosage depends on the type and severity of the infection. The duration of treatment depends on the course of the disease and should not exceed 14 days. It is recommended to continue therapy for at least 48–72 hours after normalization of body temperature or after microbiological tests have confirmed eradication of the causative pathogens.
Tablets should be swallowed whole, without chewing, and taken with sufficient fluid. The medication can be administered regardless of food intake.
The medication should be taken at least 2 hours before or 2 hours after administration of iron salts, zinc salts, antacids containing magnesium or aluminium, didanosine (only formulations containing aluminium or magnesium in buffering agents), and sucralfate (see section "Interaction with Other Medicinal Products and Other Types of Interactions").
The following dosage recommendations should be observed for adult patients with normal renal function, in whom creatinine clearance exceeds 50 ml/min:
| Indications |
Dose, mg |
Number of daily doses, times |
Treatment duration, days |
| Acute bacterial sinusitis |
500 |
1 |
10–14 |
| Exacerbation of chronic bronchitis |
500 |
1 |
7–10 |
| Community-acquired |
500 |
1–2 |
7–14 |
| Uncomplicated urinary tract infections (cystitis) |
250 |
1 |
3 |
| Chronic bacterial prostatitis |
500 |
1 |
28 |
| Complicated urinary tract infections |
500 |
1 |
7–14 |
| Acute pyelonephritis |
500 |
1 |
7–10 |
| Complicated skin and soft tissue infections |
500 |
1–2 |
7–14 |
Dosing for patients with impaired renal function in whom creatinine clearance is less than 50 ml/min
| Creatinine clearance |
Dosing regimen (depending on severity of infection) |
||
| 50–20 mL/min |
initial dose – 250 mg subsequent – 125 mg/24 h |
initial dose – 500 mg subsequent – 250 mg/24 h |
initial dose – 500 mg subsequent – 250 mg/12 h |
| 19–10 mL/min |
initial dose – 250 mg subsequent – 125 mg/48 h |
initial dose – 500 mg subsequent – 125 mg/24 h |
initial dose – 500 mg subsequent – 125 mg/12 h |
| < 10 mL/min (including hemodialysis and CAPD1) |
initial dose – 250 mg subsequent – 125 mg/48 h |
initial dose – 500 mg subsequent – 125 mg/24 h |
initial dose – 500 mg subsequent – 125 mg/24 h |
1 After hemodialysis or chronic ambulatory peritoneal dialysis (CAPD), additional doses are not required.
The tablets are not intended to be divided. If a lower dose is required, levofloxacin in another pharmaceutical form should be used.
Dosing in patients with hepatic impairment.
Dose adjustment is not necessary, since levofloxacin is minimally metabolized in the liver.
Dosing in elderly patients.
If renal function is normal, dose adjustment is not required.
Children.
Levofloxacin is not administered to children, as damage to joint cartilage cannot be excluded.
Overdose.
Symptoms: dizziness, impaired consciousness, seizures, nausea, and erosion of mucous membranes.
In the post-marketing period, adverse events affecting the central nervous system have been observed, including confusion, convulsions, myoclonus, hallucinations, and tremor. According to study results, administration of doses higher than therapeutic ones has been associated with QT interval prolongation.
Treatment: symptomatic and supportive. ECG monitoring should be considered, as QT interval prolongation may occur. Levofloxacin is not removed by either hemodialysis or peritoneal dialysis; there is no specific antidote.
Adverse Reactions
Infections and infestations: fungal infections, including Candida species; proliferation of other resistant microorganisms, disruption of normal intestinal flora, and development of secondary infections.
Blood and lymphatic system disorders: leukopenia, eosinophilia, thrombocytopenia, neutropenia.
Disorders of the hematopoietic and lymphatic systems
Frequency unknown (cannot be estimated from available data): bone marrow dysfunction, including aplastic anemia, pancytopenia, agranulocytosis, hemolytic anemia.
Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid shock, angioedema (see section "Special Warnings and Precautions for Use"); anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose.
Metabolism and nutrition disorders: anorexia, hypoglycemia, particularly in patients with diabetes mellitus (see section "Special Warnings and Precautions for Use"); hyperglycemia, hypoglycemic coma.
Psychiatric disorders*: insomnia, agitation, confusion, nervousness, fear states, psychotic disorders (including hallucinations, paranoia), depression, anxiety, restlessness, pathological dreams, nightmares; psychotic reactions with self-destructive behavior, including suicidal ideation or actions (see section "Special Warnings and Precautions for Use"), mania (frequency unknown).
Nervous system disorders*: dizziness, headache, somnolence, seizures, tremor, paresthesia, sensory or sensorimotor peripheral neuropathy, dysgeusia (subjective taste disturbance), including ageusia (loss of taste); parosmia (disturbance of smell), including anosmia (loss of smell); dyskinesia, extrapyramidal disorders, other disturbances of motor coordination, including during walking, loss of consciousness, benign intracranial hypertension, syncope, myoclonus (frequency unknown).
Eye disorders*: visual disturbances such as blurred vision, unclear vision; transient loss of vision.
Ear and labyrinth disorders*: vertigo, tinnitus, hearing disturbances, hearing loss.
Cardiac disorders**: tachycardia, palpitations, ventricular tachycardia, which may lead to cardiac arrest; ventricular arrhythmias and torsade de pointes arrhythmia (mainly in patients with risk factors for QT interval prolongation); QT interval prolongation on electrocardiogram (see sections "Special Warnings and Precautions for Use" ("QT interval prolongation") and "Overdose"), arterial hypotension, leukocytoclastic vasculitis.
Respiratory system disorders: dyspnea (shortness of breath), bronchospasm, allergic pneumonia.
Gastrointestinal disorders: diarrhea; nausea; vomiting; abdominal pain; dyspepsia; flatulence/bloating; constipation; hemorrhagic diarrhea, which in rare cases may indicate enterocolitis, including pseudomembranous colitis, pancreatitis.
Hepatobiliary disorders: elevated liver enzymes (ALT/AST, alkaline phosphatase, GGT); increased blood bilirubin levels; hepatitis; jaundice and severe liver injury, including cases of acute liver failure (sometimes fatal), mainly in patients with severe underlying diseases (see section "Special Warnings and Precautions for Use").
Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, increased sensitivity to sunlight and ultraviolet radiation, toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, exudative multiform erythema, hyperhidrosis, photosensitivity reactions, leukocytoclastic vasculitis, stomatitis, DRESS syndrome, localized skin rash caused by drugs, skin hyperpigmentation (frequency unknown).
Skin and mucosal reactions may sometimes occur even after the first dose.
Musculoskeletal and connective tissue disorders*: tendon disorders (see sections "Contraindications", "Special Warnings and Precautions for Use"), including tendon inflammation (tendinitis) (e.g., Achilles tendon), arthralgia, myalgia, tendon rupture (e.g., Achilles tendon), ligament rupture, muscle rupture, arthritis. Muscle weakness is possible, which may be particularly significant in patients with severe myasthenia gravis, rhabdomyolysis.
Renal and urinary disorders: increased serum creatinine levels, acute kidney injury (e.g., due to interstitial nephritis).
General disorders: asthenia, increased body temperature (pyrexia), pain (including back, chest, and limb pain), porphyria attacks in patients with existing porphyria.
Endocrine disorders: syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
* With use of quinolones and fluoroquinolones, very rare cases of prolonged (lasting several months or years), disabling, and potentially irreversible serious adverse reactions have been reported, sometimes affecting multiple organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disorders, and disturbances of hearing, vision, taste, and smell), in some cases in the absence of risk factors (see section "Special Warnings and Precautions for Use").
** In patients receiving fluoroquinolones, cases of aneurysm and dissection of the aorta, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported (see section "Special Warnings and Precautions for Use").
Shelf life. 3 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging.
7 tablets per blister; 1 or 2 blisters per carton.
Prescription category. Prescription only.
Manufacturer.
ASTRAFAM LLC, Ukraine.
Manufacturer's address and place of business.
6 Kyivska Street, Vyshneve, Kyiv-Sviatoshyn District, Kyiv Oblast, 08132, Ukraine.