Bactoflox (Solution) Instructions for Use

Marketing Authorization Holder

IST-Pharm, LLC (Russia)

Manufactured By

IST-Pharm, LLC (Russia)

Or

Pharmasintez-Tyumen, LLC (Russia)

ATC Code

J01MA12 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN WHO registered)

Dosage Form

Bactoflox

Solution for infusion 5 mg/1 ml: bottle 100 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for infusion transparent or slightly opalescent, greenish-yellow in color.

Excipients : sodium chloride – 9 mg, hydrochloric acid – 1.2-1.6 mg, sodium hydroxide – 0-0.3 mg, water for injection – up to 1 ml.

Theoretical osmolarity: 322 mOsm/l.

100 ml – polyethylene bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Systemic antibacterial agents; quinolone derivatives; fluoroquinolones

Pharmacological Action

A synthetic broad-spectrum antibacterial agent from the fluoroquinolone group, the levorotatory isomer of ofloxacin. Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of microbial cells.

Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

Aerobic gram-positive microorganisms Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I), Staphylococcus aureus methi-S, Staphylococcus epidermidis methi-S, Staphylococcus spp. (CNS), Streptococcus groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R, Streptococcus pyogenes, Streptococcus viridans peni-S/R.

Aerobic gram-negative microorganisms Acinetobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (β+/β-), Morganella morganii, Neisseria gonorrhoeae non-PPNG/PPNG, Neisseria meningitidis, Pasteurella spp. (including Pasteurella dagmatis, Pasteurella multocida, Pasteurella canis), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas aeruginosa, Pseudomonas spp. (including Pseudomonas aeruginosa), Salmonella spp., Serratia spp. (including Serratia marcescens).

Anaerobic microorganisms Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus, Propionibacterium spp., Veillonella spp.

Other microorganisms Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp. (including Legionella pneumophila), Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Ricketsia spp., Ureaplasma urealyticum.

Moderately susceptible microorganisms aerobic gram-positive microorganisms – Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R, Staphylococcus liaemolyticus methi-R; aerobic gram-negative microorganisms – Campylobacter jejuni, Campylobacter coli; anaerobic microorganisms – Prevotella spp., Porphyromonas spp.

Microorganisms resistant to levofloxacin aerobic gram-positive microorganisms – Staphylococcus aureus methi-R, Staphylococcus coagulase-negative methi-R, Corynebacterium jeikeium; aerobic gram-negative microorganisms – Alcaligenes xylosoxidans; anaerobic microorganisms – Bacteroides thetaiotaomicron; other microorganisms – Mycobacterium avium.

Pharmacokinetics

The pharmacokinetics of levofloxacin are linear in the dose range from 50 to 1000 mg. After a 60-minute IV infusion of levofloxacin at a dose of 500 mg to healthy volunteers, the mean C_max in blood plasma was 6.2 µg/ml. When 500 mg of levofloxacin is administered once or twice daily, C_ss in blood plasma is reached within 48 hours. Plasma protein binding is 30-40%. The V_d of levofloxacin averages 100 L after single and multiple IV administration of 500 mg, indicating good penetration of levofloxacin into the organs and tissues of the body. Levofloxacin penetrates well into the bronchial mucosa, epithelial lining fluid, alveolar macrophages, lung tissue, alveolar fluid, cortical and cancellous bone tissue, and prostate tissue. Levofloxacin poorly penetrates into the cerebrospinal fluid. High concentrations of levofloxacin are created in the urine, several times higher than the concentrations of levofloxacin in blood plasma.

Levofloxacin is minimally metabolized (5% of the administered dose) to form dimethyllevofloxacin and Levofloxacin-N-oxide, which are excreted by the kidneys. After IV administration, Levofloxacin is relatively slowly eliminated from the blood plasma (T_1/2 – 6-8 hours), mainly in the urine (more than 85% of the administered dose). The total clearance of levofloxacin after a single 500 mg dose was 175±29.2 ml/min.

In renal failure, the pharmacokinetics of levofloxacin change. As renal function deteriorates, urinary excretion and renal clearance decrease, and T_1/2 increases.

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin: complicated urinary tract infections and pyelonephritis; chronic bacterial prostatitis; for the complex treatment of drug-resistant forms of tuberculosis; prevention and treatment of anthrax with airborne infection.

For the treatment of the following infectious and inflammatory diseases, Levofloxacin can be used only as an alternative to other antimicrobial drugs: community-acquired pneumonia; complicated skin and soft tissue infections; uncomplicated cystitis.

ICD codes

Dosage Regimen

Administered intravenously by drip. The dosage regimen is set individually, depending on the indications, clinical situation, and sensitivity of the pathogen. The duration of treatment varies depending on the course of the disease. Treatment with levofloxacin is recommended to continue for at least 48-72 hours after normalization of body temperature or reliable eradication of the pathogen.

Adverse Reactions

Infections and parasitic diseases uncommon – fungal infections, development of resistance of pathogenic microorganisms.

From the hematopoietic system uncommon – leukopenia, eosinophilia; rare – neutropenia, thrombocytopenia; frequency unknown – pancytopenia, agranulocytosis, hemolytic anemia.

From the immune system rare – angioedema; frequency unknown – anaphylactic shock, anaphylactoid shock.

From metabolism rare – hypoglycemia, especially in patients with diabetes mellitus; frequency unknown – hyperglycemia, hypoglycemia, up to the development of hypoglycemic coma.

Mental disorders common – insomnia; uncommon – feeling of restlessness, anxiety, confusion; rare – mental disorders (e.g., hallucinations, paranoia), depression, agitation, sleep disorders, nightmares; frequency unknown – mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts, nervousness, memory impairment, delirium (including attention impairment, disorientation).

From the nervous system common – headache, dizziness; uncommon – drowsiness, tremor, dysgeusia; rare – paresthesia, convulsions; frequency unknown – peripheral sensory neuropathy, peripheral sensorimotor neuropathy, dyskinesia, extrapyramidal disorders, ageusia, parosmia, including loss of smell, syncope, increased intracranial pressure (benign intracranial hypertension, pseudotumor cerebri).

From the organ of vision rare – visual disturbances such as blurred vision; frequency unknown – transient loss of vision, uveitis.

From the organ of hearing and labyrinthine disorders uncommon – vertigo; rare – tinnitus; frequency unknown – hearing loss, hearing impairment.

From the cardiovascular system common – phlebitis; rare – decreased blood pressure, sinus tachycardia, palpitations; frequency unknown – QT interval prolongation, ventricular arrhythmias, ventricular tachycardia, torsades de pointes, which can lead to cardiac arrest.

From the respiratory system uncommon – dyspnea; frequency unknown – bronchospasm, allergic pneumonitis.

From the digestive system common – diarrhea, vomiting, nausea; uncommon – abdominal pain, dyspepsia, flatulence, constipation; frequency unknown (post-marketing data) – hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis, pancreatitis.

From the liver and biliary tract common – increased ALT, AST, ALP, GGT activity; uncommon – increased blood bilirubin concentration; frequency unknown (post-marketing data) – severe liver failure, including cases of acute liver failure (sometimes fatal), especially in patients with severe underlying disease (e.g., sepsis); hepatitis, jaundice.

From the skin and subcutaneous tissues uncommon – rash, itching, urticaria, hyperhidrosis; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions, fixed drug eruption, leukocytoclastic vasculitis, stomatitis.

From the musculoskeletal system uncommon – arthralgia, myalgia; rare – tendon damage, including tendinitis (e.g., Achilles tendon), muscle weakness, which may be particularly dangerous in patients with myasthenia gravis; frequency unknown – rhabdomyolysis, tendon rupture (e.g., Achilles tendon), ligament rupture, muscle rupture, arthritis.

From the urinary system uncommon – increased serum creatinine concentration; rare – acute renal failure (e.g., due to the development of interstitial nephritis).

Other common – reaction at the injection site (pain, skin redness); uncommon – asthenia; rare – pyrexia; frequency unknown – pain (including back, chest, limb pain); very rare – porphyria attacks in patients with porphyria.

Contraindications

Hypersensitivity to levofloxacin or other quinolones; epilepsy; myasthenia gravis; history of tendon lesions when using fluoroquinolones; age under 18 years; pregnancy, breastfeeding period.

With caution should be used in patients predisposed to the development of seizures; in patients simultaneously taking drugs that lower the seizure threshold of the brain (such as fenbufen, theophylline); with latent or manifested glucose-6-phosphate dehydrogenase deficiency; with impaired renal function; in patients with known risk factors for QT interval prolongation or with congenital long QT syndrome; in heart disease (heart failure, myocardial infarction, bradycardia); with simultaneous use of drugs that can prolong the QT interval (class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics); in patients with diabetes mellitus receiving oral hypoglycemic drugs or insulin preparations; in patients with severe adverse reactions to other fluoroquinolones (such as severe neurological reactions), with psychoses or in patients with a history of mental illness; in elderly patients; after transplantation; with concomitant use of corticosteroids (increased risk of tendinitis and tendon rupture); in patients with a family history of aortic aneurysm or in patients with a diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions predisposing to the development of aortic aneurysm or aortic dissection.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

In case of impaired liver function, no dose adjustment is required.

Use in Renal Impairment

Should be used with caution in case of impaired renal function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

Hospital-acquired infections caused by Pseudomonas aeruginosa may require combination therapy.

The prevalence of acquired resistance of isolated strains of microorganisms may vary by geographic region and over time. Therefore, information on resistance to levofloxacin in a particular country is required. For the treatment of severe infections or in case of treatment failure, a microbiological diagnosis should be established with isolation of the pathogen and determination of its sensitivity to levofloxacin.

There is a high probability that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including Levofloxacin. Therefore, Levofloxacin is not recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus, unless laboratory tests confirm the sensitivity of this microorganism to levofloxacin.

The use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions from various body systems, which may develop simultaneously in the same patient. Adverse reactions caused by fluoroquinolones include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, as well as side effects from the nervous system (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions can develop within a few hours to several weeks after starting levofloxacin therapy. The development of these adverse reactions has been observed in patients of all ages and without the presence of prior risk factors. At the first signs or symptoms of any serious adverse reactions, the use of levofloxacin should be stopped immediately. The use of fluoroquinolones, including levofloxacin, should be avoided in patients who have experienced any of these serious adverse reactions.

During the infusion, increased heartbeat and a transient decrease in blood pressure may be observed. In rare cases, vascular collapse may develop. If a pronounced decrease in blood pressure is observed during the infusion, the administration of levofloxacin should be stopped immediately.

Levofloxacin should be used with great caution in patients predisposed to seizures: patients with previous CNS lesions, such as stroke, severe traumatic brain injury; patients simultaneously taking drugs that lower the seizure threshold of the brain (for example, theophylline; fenbufen and other NSAIDs). If seizures develop, treatment with levofloxacin should be discontinued.

If pseudomembranous colitis is suspected, treatment with levofloxacin should be discontinued immediately and specific antibiotic therapy (oral vancomycin, teicoplanin, or metronidazole) should be initiated promptly. Drugs that inhibit intestinal peristalsis are contraindicated.

Tendinitis, which rarely occurs during the use of quinolones, can sometimes lead to tendon rupture, including the Achilles tendon, and may be bilateral. This adverse reaction may develop within 48 hours after starting treatment or several months after completing fluoroquinolone therapy. Elderly patients are more predisposed to developing tendinitis; in patients taking fluoroquinolones, the risk of tendon rupture may be increased with the concomitant use of corticosteroids. Furthermore, patients after transplantation have an increased risk of developing tendinitis, so caution is recommended when prescribing fluoroquinolones to this category of patients. If tendinitis or tendon rupture is suspected, treatment with levofloxacin should be discontinued immediately and appropriate treatment for the affected tendon should be initiated, for example, by ensuring its adequate immobilization.

Levofloxacin can cause serious, potentially life-threatening hypersensitivity reactions (angioedema, anaphylactic shock) even with the initial doses. If these develop, the drug administration should be discontinued immediately.

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been observed with the use of levofloxacin. If any skin or mucous membrane reactions occur, the patient should immediately consult a doctor and not continue treatment until after consultation.

Cases of liver necrosis, including fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis. Patients should be warned to discontinue treatment and seek immediate medical attention if signs and symptoms of liver damage appear, such as anorexia, jaundice, dark urine, skin itching, and abdominal pain.

Since Levofloxacin is excreted primarily by the kidneys, in patients with impaired renal function, mandatory monitoring of renal function and dosage regimen adjustment is required. When treating elderly patients, it should be considered that this patient group often has impaired renal function.

Although photosensitivity develops very rarely with the use of levofloxacin, to prevent its occurrence, patients are advised to avoid intense sunlight or artificial UV radiation (e.g., using tanning beds) during treatment and for 48 hours after completing levofloxacin treatment.

The use of levofloxacin, especially over a long period, may lead to the overgrowth of microorganisms (bacteria and fungi) resistant to it, which can cause changes in the normal human microflora, resulting in an increased risk of superinfection. Therefore, during treatment, it is necessary to regularly reassess the patient’s condition and, if superinfection develops during treatment, appropriate measures should be taken.

Patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency are predisposed to developing hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.

Cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin. During levofloxacin therapy, dysglycemia developed more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (e.g., glibenclamide) or insulin. When using levofloxacin in such patients, the risk of hypoglycemia increases, up to hypoglycemic coma. If a patient develops hypoglycemia, it is necessary to immediately discontinue levofloxacin treatment and initiate appropriate therapy. In these cases, it is recommended to switch to therapy with another antibiotic, other than fluoroquinolones, if possible. When conducting treatment with levofloxacin in elderly patients and patients with diabetes mellitus, careful monitoring of blood glucose concentration is recommended.

In patients receiving therapy with fluoroquinolones, including Levofloxacin, cases of sensory and sensorimotor peripheral neuropathy have been reported, the onset of which can be rapid. If a patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the potential risk of developing irreversible changes. Fluoroquinolones should not be prescribed to patients with a history of clinical cases indicating peripheral neuropathy.

Fluoroquinolones, including Levofloxacin, are characterized by neuromuscular blocking activity and can increase muscle weakness in patients with myasthenia gravis. In the post-marketing period, adverse reactions, including respiratory failure requiring mechanical ventilation and fatal outcome, have been observed, which were associated with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in patients with an established diagnosis of myasthenia gravis is not recommended.

Psychotic reactions, including suicidal thoughts/attempts, have been noted in patients using fluoroquinolones, including Levofloxacin, sometimes after a single dose of levofloxacin. If any CNS side effects develop, including mental disorders, treatment with levofloxacin should be discontinued immediately and appropriate therapy should be prescribed. In these cases, it is recommended to switch to therapy with another antibiotic, other than fluoroquinolones, if possible.

Fluoroquinolones should be used only after a thorough benefit-risk assessment and consideration of other therapy options in patients with a family history of aortic aneurysm, or in patients with a diagnosed aortic aneurysm and/or aortic dissection, or in the presence of other risk factors or conditions predisposing to the development of aortic aneurysm or aortic dissection (e.g., Marfan syndrome, vascular type Ehlers-Danlos syndrome, Takayasu’s arteritis, giant cell arteritis, Behçet’s disease, arterial hypertension, atherosclerosis).

If any visual disturbances develop, an immediate consultation with an ophthalmologist is necessary.

In patients receiving levofloxacin therapy, urine opiate tests may yield false-positive results, which should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and subsequently lead to false-negative results in the bacteriological diagnosis of tuberculosis.

Effect on the Ability to Drive Vehicles and Operate Machinery

Side effects such as dizziness or vertigo, drowsiness, and visual disturbances can reduce psychomotor reactions and the ability to concentrate. This may pose a certain risk when engaging in activities requiring rapid psychomotor reactions and the ability to concentrate (e.g., driving a car, operating machinery, working in unstable positions).

Drug Interactions

With the simultaneous use of quinolones and theophylline, NSAIDs, and other agents that lower the seizure threshold of the brain, a pronounced decrease in the seizure threshold of the brain is possible.

In patients receiving treatment with levofloxacin in combination with indirect anticoagulants (e.g., warfarin), an increase in prothrombin time/INR and/or the development of bleeding, including severe bleeding, has been observed. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary.

Caution should be exercised with the simultaneous use of drugs that impair renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, especially in patients with renal failure.

Concomitant administration of corticosteroids increases the risk of tendon rupture.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.