Zolev (levofloxacin) solution for infusions 5 mg/ml. 100 ml. vial №1

$15.90

Infections caused by drug-sensitive microorganisms: non-hospital pneumonia; complicated infections of the skin and soft tissues; complicated infections of the urinary tract (including pyelonephritis); chronic bacterial prostatitis.

Category: Manufacturer: India

Description

Zolev solution storage:

active substance: levofloxacin;

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

Excipients

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

Dosage form

Solution for infusion.

Basic physical and chemical properties: transparent solution of greenish-yellow color.

Pharmacotherapeutic group

Antibacterial agents of the quinolone group. Fluoroquinolones.

ATC code J01M A12.

Pharmacological properties:

Pharmacodynamics

Levofloxacin is a synthetic antibacterial agent from the group of fluoroquinolones, S ‑ enantiomer of a racemic mixture of the drug ofloxacin.

Mechanism of action

As an antibacterial drug from the group of fluoroquinolones, levofloxacin acts on the complex of DNA-DNA gyrase and topoisomerase IV.

Pharmacokinetic / pharmacodynamic ratio

The degree of bacterial activity of levofloxacin depends on the ratio of the maximum serum concentration (Cmax) or the area under the pharmacokinetic curve (AUC) and the minimum inhibitory (inhibitory) concentration (MIC).

Mechanism of resistance

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

Due to the mechanism of action, there is usually no cross-resistance between levofloxacin and other classes of antibacterial agents.

Antibacterial spectrum

The prevalence of resistance may vary geographically and over time for selected species. It is desirable to obtain local information on resistance, especially in the treatment of severe infections. If necessary, you should seek the advice of a specialist, when the local prevalence of resistance is such that the usefulness of the drug, at least in some types of infections, is questionable.

Usually sensitive species

Aerobic gram-positive bacteria: Staphylococcus aureusmeticillin-sensitive, Staphylococcus saprophyticus, Streptococci, group C and G, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic gram-negative bacteria: Burkholderia cepacia, Eikenella corrodens, Haemophilus influenzae, Haemophilu sparainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia.

Anaerobic bacteria: Peptostreptococcus.

Others: Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamidia trachomatis, Legionella pneumophila, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum.

Species for which acquired (secondary) resistance can be problematic

Aerobic gram-positive bacteria: Enterococcus faecalis, Staphylococcus aureusmethicillin-resistant, Staphylococcuscoagulasespp.

Aerobic gram-negative bacteria: Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Morganella morganii, Proteus mirabilis, Providencia stuartii, Pseudomons Seratiga aerugin.

Anaerobic bacteria: Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides vulgatus, Clostridium difficile.

Other data

Nosocomial infections caused by P.Aeruginosa, may require combination therapy.

Pharmacokinetics

Absorption. There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration.

After intravenous administration, the drug accumulates in the bronchial mucosa and bronchial secretions of lung tissue (concentration in the lungs exceeds that in blood plasma), urine. Levofloxacin enters the cerebrospinal fluid poorly.

Distribution. Approximately 30-40% of levofloxacin is bound to serum protein. The cumulative effect of levofloxacin with repeated use of 500 mg 1 time per day is almost absent. There is a small but predictable cumulative effect after doses of 500 mg twice daily. Stable state is reached within 3 days.

Penetration into tissues and body fluids

Penetration into the bronchial mucosa, bronchial secretion of lung tissue (BSTL). The maximum concentration of levofloxacin in the bronchial mucosa and bronchial lung secretion after administration of 500 mg orally was 8.3 μg / g and 10.8 μg / ml, respectively. These values ​​were achieved within 1 hour after taking the drug.

Penetration into lung tissue. The maximum concentration of levofloxacin in lung tissue after administration of 500 mg orally was approximately 11.3 μg / g and was reached 4-6 hours after administration of the drug. The concentration in the lungs exceeds that in blood plasma.

Penetration into the contents of the bladder. After 3 days of administration of the drug in doses of 500 mg1 times or 2 times a day, the maximum concentrations of levofloxacin 4-6.7 μg / ml in the contents of the bladder were reached within 2-4 hours, respectively, after taking the drug.

Penetration into the cerebrospinal fluid. Levofloxacin does not penetrate well into the cerebrospinal fluid.

Penetration into prostate tissue. After administration of 500 mg of levofloxacin once daily for 3 days, the average concentration in prostate tissue reached 8.7 μg / g, 8.2 μg / g and 2 μg / g, respectively, after 2 hours, 6 hours at 24 years; the average prostate / plasma concentration ratio was 1.84.

Urinary concentration. The mean urinary concentration 8-12 hours after a single oral dose of 150 mg, 300 mg or 500 mg of levofloxacin was 44 mg / l, 91 mg / l and 200 mg / l, respectively.

Biotransformation. Levofloxacin is metabolized to a very small extent, the metabolites are dimethyl во levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the drug excreted in the urine. Levofloxacin is stereochemically stable and is not subject to inversion of the choral structure.

Breeding. After oral and intravenous administration, levofloxacin is excreted from the blood plasma relatively slowly (half-life is 6-8 hours), usually excreted by the kidneys (more than 85% of the administered dose).

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

Elderly patients

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

Gender differences

A separate analysis of female and male patients showed slight differences in the pharmacokinetics of levofloxacin depending on gender. There is no evidence that these gender differences are clinically significant.

Clinical characteristics

Indication

Infections caused by drug-sensitive microorganisms:

  • community-acquired pneumonia;
  •  complicated skin and soft tissue infections
  •  complicated urinary tract infections (including pyelonephritis);
  •  chronic bacterial prostatitis
  •  pulmonary form of anthrax: prevention after contact and treatment.

Contraindication

Hypersensitivity to any component of the drug, to levofloxacin or to other quinolones. Epilepsy, side effects from tendons after previous use of quinolones. Pregnancy and breastfeeding. Children’s age (up to 18 years).

Interaction with other drugs and other types of interactions

Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs (NSAIDs). Levofloxacin did not show any pharmacokinetic interactions with theophylline. There may be a marked decrease in cerebral convulsive threshold with the introduction of quinolones simultaneously with theophylline, NSAIDs or other drugs that reduce the convulsive threshold. Levofloxacin concentrations in the presence of fenbufen were approximately 13% higher than in levofloxacin alone.

Probenecid and cimetidine. Have a statistically significant effect on the elimination of levofloxacin; renal clearance of levofloxacin was reduced when used with cimetidine (24%) and probenecid (34%). Levofloxacin should be used with caution in combination with drugs that affect the secretion of the renal tubules (probenecid and cimetidine), especially in patients with impaired renal function.

Cyclosporine. The half-life of cyclosporine increases by 33% when it is co-administered with levofloxacin.

Vitamin K antagonists Due to the possible occurrence of bleeding in patients taking levofloxacin in combination with any vitamin K antagonist (eg warfarin), coagulation tests should be monitored if these drugs are used concomitantly.

Drugs 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 (eg class IA and III antiarrhythmics, tricyclic antidepressants and macrolides, antipsychotics).

The pharmacokinetics of levofloxacin did not change when co-administered with calcium carbonate, digoxin, glibenclamide, ranitidine, warfarin

The use of levofloxacin with alcohol is not recommended

Concomitant use with glucocorticoids increases the risk of tendon rupture.

Features of application

Patients with severe cerebral atherosclerosis, cerebrovascular disorders should be cautious when using the drug.

Renal failure

Levofloxacin is excreted mainly by the kidneys, so patients with renal insufficiency require dose adjustment.

Renal and hepatic function should be monitored throughout the course of treatment. Cases of necrotic hepatitis, up to life-threatening hepatic failure, have been reported with levofloxacin, mainly in patients with severe underlying conditions such as sepsis. Patients should be advised to discontinue treatment and consult a physician if symptoms of hepatic impairment, such as anorexia, jaundice, black urine, pruritus, or abdominal pain, occur.

Levofloxacin should be discontinued if side effects occur, especially from the central nervous system and allergic reactions that may occur after the first dose.

Patients with a predisposition to seizures

Quinolones can lower the seizure threshold and provoke the development of seizures.

Levofloxacin is contraindicated in patients with a history of epilepsy.

Photosensitivity reactions have been reported during treatment with levofloxacin

In order to prevent photosensitivity reactions, patients taking levofloxacin should avoid sunlight and UV rays (artificial ultraviolet lamps, solarium) due to possible photosensitization while taking levofloxacin or within 48 hours after stopping levofloxacin.

In very severe pneumonia caused by pneumococci, the drug may not give the optimal therapeutic effect. Combination therapy may be required for nosocomial infections caused by P. aeruginosa and severe cases of pneumococcal pneumonia. The prevalence of acquired resistance to the drug among certain types of pathogens may vary depending on the geographical region and change over time. Therefore, local information on pathogen resistance is required; it is recommended to establish a microbiological diagnosis with isolation of the pathogen and demonstration of its sensitivity to antibiotics, especially in case of severe infections or lack of proper response to therapy.

For methicillin-resistantS. Aureus (MRSA) has a very high probability of resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be MRSA, unless laboratory tests have confirmed the susceptibility of the pathogen to levofloxacin.

The recommended rate of infusion solution should be followed for at least 30 minutes for a dose of 250 mg and 60 minutes for a dose of 500 mg. With regard to ofloxacin, tachycardia and a temporary increase in blood pressure are known during infusion. In rare cases, there may be a consequence of a sharp drop in blood pressure, circulatory collapse. If a marked decrease in blood pressure is observed during the administration of levofloxacin (l -isomer of ofloxacin), the administration should be stopped immediately.

In isolated cases, patients may develop tendinitis. Tendinitis most often affects the Achilles tendon and can lead to tendon rupture. The risk of developing tendinitis and tendon rupture is increased in elderly patients and in patients taking corticosteroids. Therefore, patients taking levofloxacin should be closely monitored. Patients with symptoms of tendinitis should consult a physician before starting treatment. If tendinitis is suspected, treatment with the drug should be stopped immediately and appropriate treatment of the affected tendon should be initiated (eg by immobilization).

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

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

Patients with latent or advanced glucose-6-phosphate dehydrogenase deficiency may be prone to hemolytic reactions if treated with quinolone antibacterial agents. Therefore, levofloxacin should be used with caution.

Exacerbation of myasthenia gravis. Fluoroquinolones, including levofloxacin, have a neuromuscular blockade effect and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing setting, patients with myasthenia gravis using fluoroquinolones were associated with serious adverse reactions, including pulmonary insufficiency requiring respiratory support and deaths. Levofloxacin is not recommended for use in patients with a history of known myasthenia gravis.

Psychotic reactions.

Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. Very rarely, they have led to suicidal thoughts and self-destructive behavior, sometimes even after a single dose of levofloxacin.

When using the drug should refrain from drinking alcohol

Severe bullous reactions.

Severe bullous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with levofloxacin. If bullous reactions occur, levofloxacin should be discontinued immediately, a doctor should be consulted and appropriate treatment instituted.

Patients taking vitamin K antagonists should have their blood clotting levels monitored while taking levofloxacin and vitamin K antagonists (warfarin) due to the potential risk of increased blood clotting (prothrombin time / EOM) and / or bleeding.

Levofloxacin can cause severe, potentially lethal hypersensitivity reactions (such as angioneurotic edema, up to anaphylactic shock), even after the initial dose. In this case, patients should stop treatment immediately and consult a doctor.

As with other quinolones, hypoglycaemia has been reported, especially in patients with diabetes mellitus receiving concomitant oral hypoglycaemic therapy (eg glibenclamide) or insulin.

Careful monitoring of blood glucose levels in patients with diabetes is recommended. Cases of hypoglycemic coma have been reported.

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

  •  congenital QT prolongation syndrome;
  •  concomitant use of drugs that prolong the QT interval (including antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotic drugs);
  •  uncorrected electrolyte imbalance (eg hypokalemia, hypomagnesemia);
  •  old age of the patient;
  •  heart disease (eg heart failure, myocardial infarction, bradycardia).

Peripheral neuropathy

Cases of sensory or sensorimotor peripheral neuropathy, which may occur rapidly, have been reported in patients taking fluoroquinolones, including levofloxacin. Levofloxacin should be discontinued if the patient has symptoms of neuropathy to prevent irreversible conditions.

Opiates

ceiving levofloxacin, urinary opiates may be false-positive. It may be necessary to confirm positive results for opiates using more specific methods.

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

Use during pregnancy or breastfeeding

During pregnancy or breastfeeding, the drug is contraindicated. If pregnancy is diagnosed during treatment, the doctor should be informed. If necessary, breast-feeding should be discontinued.

Ability to influence the speed of reaction when driving a car or other machinery

In some patients, the drug can cause headache, dizziness / vertigo, drowsiness, insomnia, visual disturbances, confusion, movement disorders, so you should refrain from driving or working with complex mechanisms that require increased attention and speed of psychomotor reactions.

Method of application and dosage

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

Under room lighting, the solution for intravenous administration can be stored for up to 3 days without protection from light.

Taking into account the biological equivalence of oral and parenteral forms, the same dosage is possible.

The dosage depends on the type and severity of the infection

The recommended dosage is for adults with normal renal function in whom creatinine clearance is greater than 50 ml / minute.

Mixing with other solutions for infusions

Levofloxacin is compatible with the following infusion solutions:

0.9% sodium chloride solution, 5% glucose monohydrate, 2.5% glucose in Ringer’s solution, multicomponent solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

Children

The use of the drug is contraindicated in children and adolescents, as it is possible damage to articular cartilage.

Overdose

Symptoms: dizziness, hallucinations, disturbance of consciousness, confusion, convulsions, tremor, prolongation of the QT interval, increased manifestations of other adverse reactions.

Treatment: symptomatic and supportive. ECG monitoring should be considered as QT interval prolongation is possible. Levofloxacin is not removed by hemodialysis or peritoneal dialysis; there is no specific antidote.

Adverse reactions

Allergic reactions: anaphylactoid shock, urticaria, bronchospasm / dyspnea, allergic pneumonitis, dyspnea, anaphylactic shock; severe bullous rash, hypersensitivity (hypersensitivity), Quincke’s edema.

Such reactions can sometimes be observed even after the first dose within minutes or hours after application.

From the skin and subcutaneous tissues: rash, itching, redness of the skin, urticaria, hypersensitivity to sunlight and ultraviolet radiation, severe bullous rashes such as toxic epidermal necrolysis (Lyell’s syndrome), Stevensnapper’s syndrome – John Steps , leukocytoplastic vasculitis.

From the digestive tract and metabolism: nausea, diarrhea; anorexia, vomiting, abdominal pain, dyspepsia, bloating, constipation; diarrhea with blood impurities, which in isolated cases may indicate enterocolitis, including pseudomembranous colitis; hypoglycemia, especially in patients with diabetes mellitus; hypoglycemic coma, pancreatitis; stomatitis.

From the central nervous system: headache, dizziness / vertigo, drowsiness, insomnia, nervousness; paresthesia, tremor, dyskinesia, extrapyramidal symptoms, confusion, convulsions, anxiety, depression, psychotic reactions, agitation, anxiety; hypoaesthesia, sensory or sensorimotor peripheral neuropathy, hallucinations, psychotic reactions with self-destructive behavior, including suicidal tendencies, nightmares, benign intracranial hypertension.

From the cardiovascular system: tachycardia, hypotension; QT prolongation, palpitations, ventricular tachycardia, which may lead to cardiac arrest; ventricular arrhythmia and torsade de pointes arrhythmia (mainly in patients with risk factors for QT prolongation), vasculitis, collapse.

From the musculoskeletal system: arthralgia, myalgia, tendon lesions, including tendinitis (eg Achilles tendon); rupture of ligaments, muscles, rupture of tendons (eg, Achilles), this side effect can occur within 48 hours of treatment and affect the Achilles tendon in both legs; bilateral muscle weakness, especially dangerous for patients with malignant myasthenia; rhabdomyolysis, arthritis, pain in the lower extremities, joint pain.

From the liver: increased liver enzymes (ALT / AST, alkaline phosphatase, GGTP); increase in bilirubin; hepatic reactions such as hepatitis, jaundice and severe liver damage, including acute fatal liver failure, have been reported with levofloxacin, predominantly in patients with severe underlying disease.

From the kidneys: increased serum creatinine; acute renal failure (for example, due to interstitial nephritis).

From the blood system: eosinophilia, leukopenia; neutropenia, thrombocytopenia;

agranulocytosis, hemolytic anemia, pancytopenia; hyperglycemia, hypoglycemic coma; Signs of hypoglycemia may be increased appetite, nervousness, increased sweating, trembling limbs, psychotic disorders (including hallucinations, paranoia), anxiety, fear, nightmares, anosmia, ageusia, dyskinesia, fainting, benign intracranial hyper.

From the senses: visual and auditory disorders, ringing in the ears, impaired taste and perception of odors, blurred vision, temporary vision loss, hearing loss, taste and smell, vertigo.

Local reactions: changes at the injection site, including redness, pain, phlebitis.

Others: phlebitis, asthenia, candidiasis, development of secondary infections; pyrexia, allergic pneumonitis, fever, chills.

Infections and invasions: mycoses (and proliferation of other resistant microorganisms).

Other side effects associated with fluoroquinolones may include extrapyramidal symptoms and other muscle disorders and incoordination, allergic vasculitis, and attacks of porphyria in patients with porphyria.

From the respiratory system: shortness of breath, bronchospasm, allergic component.

Expiration date

2 years.

Storage conditions

Store in the original package at a temperature not exceeding 25 oC.

Keep out of reach of children.

Incompatibility

The product should not be mixed with heparin or alkaline solutions (eg sodium bicarbonate), with drugs other than those listed in the section “Method of administration and dosage”.

Packaging

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