Levofloxacin-SOLOfarm - instructions for use, dose, side effects, contraindications

The antibacterial activity of ofloxacin is mainly related to Lisomer. As an antibacterial preparation of the class of fluoroquinolones, levofloxacin blocks the DNA-gyre (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks (deoxyribonucleic acid), suppresses DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes.

The mechanism of development of resistance

Resistance to levofloxacin can develop, primarily, by two main mechanisms, namely: a decrease in the intracellular concentration of the drug or changes in the targets of the action of the drug.The change in the targets - two bacterial enzymes of DNA-gyrase and topoisomerase IV - are the result of mutations in chromosomal genes encoding DNA-gyrase (gyrA and gyrB) and topoisomerase IV (parFROM and parE; grlA and grlB the Staphylococcus aureus). The stability of the drug due to a low intracellular concentration develops as a result of a change in the system of porin channels of the outer membrane of the cell, which leads to a decrease in the intake of fluoroquinolone into gram-negative bacteria, or from efflux pumps. Efflux-mediated resistance is described in relation to pneumococci (PmrA), staphylococci (NorA), anaerobic and gram-negative bacteria. Plasmid-mediated resistance to quinolones (determined based on the gene qnr) was discovered in relation to Klebsiella pneumoniae and Escherichia coli. It is possible to develop cross-resistance between fluoroquinolones. Single mutations may not lead to clinical stability, but multiple mutations cause clinical resistance to all drugs belonging to the class of fluoroquinolones. The altered porins of external membranes and efflux systems can have broad substrate specificity, affecting several classes of antibacterial agents and leading to multiple resistance.

Installed in vitro and confirmed in clinical studies the effectiveness of Gram-positive aerobes - Enterococcus faecalis. Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus saprophyticus, Streptococcus pneumoniae (including multidrug-resistant strains -MDRSP), Streptococcus pyogenes; gram-negative aerobes - Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus paraintluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens and other microorganisms - Chlamydia pneumoniae, Mycoplasma pneumoniae. With respect to the majority (≥90%) of strains of the following microorganisms in vitro the minimal suppressive concentrations of levofloxacin (2 μg / ml or less) have been established, however, the efficacy and safety of the clinical use of levofloxacin in the treatment of infections caused by these pathogens has not been established in adequate and well-controlled studies: gram- Staphylococcus haemolyticus, Streptococcus (Group C/F), Streptococcus (Group G), Streptococcus agalactiae, Streptococcus milleri. Streptococcus viridans; gram-negative aerobes - Acinetobacter lwoffii, Acinetobacter baumannii, Bordetella pertussis, Citrobacter (diversus) koseri, Citrobacter freundii, Enterobacter aerogenes, Enterobacter sakazakii, Klebsiella oxytoca, Morganella morganii, Pantoea (Enterobacter) agglomerans, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas fluorescens; Gram-positive anaerobes - Clostridium perfringens.

Sensitive microorganisms: aerobic Gram-positive microorganisms - Corynebacterium diphtheriae, Enterococcus spp., including Enterococcus faecalis, Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive / leukotoxin-containing / moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus spp. groups viridans (penicillin-sensitive / resistant strains); aerobic gram-negative microorganisms - Acinetobacter spp., including Acinetobacter baumannii, Acinetobacillus actinomycetecomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp., including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., including Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (producing and non-producing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and non-producing penicillinase strains), Neisseria meningitidis, Pasteurella spp., including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus vulgaris, Providencia spp., including Providencia rettgeri, Providencia stuartii, Pseudomonas spp., including Pseudomonas aeruginosa, Serratia spp., including Serratia marcescens, Salmonella spp.; anaerobic microorganisms - Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veilonella spp.; other microorganisms - Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae. Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (MIC of more than 4 mg / l): aerobic gram-positive microorganisms - Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium. Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains); Aerobic Gram-negative microorganisms - Burkhoideria cepacia, Campylobacter jejuni, Campylobacter coli; anaerobic microorganisms - Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Resistant microorganisms (MIC of more than 8 mg / ml): aerobic Gram-positive microorganisms - Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), others Staphylococcus spp. (coagulase-negative methicillin-resistant strains); aerobic gram-negative microorganisms - Alcaligenes xylosoxidane; other microorganisms - Mycobacterium avium.

Minimum inhibitory concentrations of levofloxacin for certain microorganisms

Microorganism	Sensitive, mg / ml	Resistant, mg / ml
Pseudomonas spp.	≤1	>2
Staphylococcus spp.	≤1	>2
Streptococcus	≤1	>2
Streptococcus pneumoniae	≤1	>2
Haemophilus influenzae	≤1	>1
Moraxella catarrhalis	≤1	>2

Activity of levofloxacin in vitro approximately 2 times higher than for ofloxacin against representatives Enterobacteriaceae, Pseudomonas aeruginosa and Gram-positive microorganisms.

In the case of levofloxacin in the treatment of chlamydial diseases of the organs of vision, concomitant therapy is required.

The degree of sensitivity of microorganisms to levofloxacin can have significant geographical differences.

The maximum concentration of levofloxacin, obtained with the use of drops for eye 0.5%, more than 100 times greater than the minimum inhibitory concentration (MIC) of levofloxacin for sensitive microorganisms.

Pharmacokinetics:

After instillation in the eye levofloxacin well preserved in the lacrimal film. The concentration of levofloxacin in the lacrimal fluid after a single dose (1 drop) quickly reaches high values and is kept above the minimum inhibitory concentration for most sensitive eye pathogens (less than or equal to 2 μg / ml) for at least 6 hours. In studies on healthy volunteers, it was shown that the average concentrations of levofloxacin in the tear film, measured at 4 and 6 hours after topical application, were 17.0 μg / ml and 6.6 μg / ml, respectively. In five out of six volunteers, concentrations of levofloxacin were 2 μg / ml and higher 4 hours after instillation. In four out of six volunteers this concentration was preserved 6 hours after instillation. The average concentration of levofloxacin in the blood plasma after 1 hour after application is from 0.86 ng / ml on the 1st day to 2.05 ng / ml.The maximum concentration of levofloxacin in the plasma, equal to 2.25 ng / ml, was detected on the 4th day after two days of application of the drug every 2 hours up to 8 times a day. The maximum concentrations of levofloxacin reached on day 15 are more than 1000 times lower than those concentrations observed after oral doses of levofloxacin.

Indications:

- Treatment of superficial bacterial infections of the eye caused by sensitive microorganisms in adults and children older than 1 year.

- Prophylaxis of complications after surgical and laser operations on the eye.

Contraindications:

Hypersensitivity to levofloxacin or to any of the components of the drug, as well as to other quinolones.

Carefully:

Childhood.

Pregnancy and lactation:

Pregnancy

There is insufficient data on the use of levofloxacin in pregnant women. The results of preclinical studies do not indicate a direct or indirect adverse effect with respect to toxic effects on reproductive function and intrauterine development. The potential risk of the drug for humans is unknown. Eye drops levofloxacin can be used during pregnancy if the potential benefit to the mother exceeds the possible risk to the fetus.

Breastfeeding period

Levofloxacin enters the breast milk. However, when levofloxacin is used in therapeutic doses, no effects on the infant are expected. Eye drops levofloxacin can be used during breastfeeding, if the potential benefit to the mother exceeds any possible risk for the infant.

Fertility

After topical application levofloxacin did not cause impairment of fertility in rats when exposed to significantly higher than the maximum dose for humans.

Dosing and Administration:

Locally, in the affected eye. The duration of the course of treatment is determined by the severity of the condition, its clinical and bacteriological characteristics. The average duration of therapy is 5 days.

1-2 drops in the affected eye (a) every two hours up to 8 times a day during the waking period during the first 2 days, then 4 times a day from 3 to 5 days.

When using several drugs, the interval between their instillations should be at least 15 minutes.

Side effects:

The incidence of adverse reactions during therapy with levofloxacin was about 10%. Most often, the severity of unwanted reactions ranged from mild to moderate severity; undesirable reactions were noted mainly from the side of the organ of vision. Information on adverse events was obtained during clinical trials and post-registration.

Immune system disorders:

Rarely (> 1/10000, <1/1000): systemic allergic reactions, including skin rash.

Rarely (<1/10000): Anaphylactic shock.

Impaired nervous system:

Infrequently (> 1/1000, <1/100): a headache.

Disorders from the side of the organ of vision:

Often (> 1/100, <1/10): burning in the eye, decreased vision, filamentous mucosal discharge in the conjunctival cavity.

Infrequently (> 1/1000, <1/100): chemosis, conjunctival injection, papillary conjunctivitis, edema of the eyelids, erythema of the eyelids, discomfort in the eye, itching in the eye, pain in the eye, dry eye syndrome, photophobia.

Disorders from the respiratory, thoracic and mediastinal organs:

Infrequently (> 1/1000, <1/100): rhinitis.

Rarely (<1/10000): laryngeal edema.

The profile of adverse events in the use of the drug in the pediatric population is comparable to that of the adult population.

Overdose:

The total amount of levofloxacin contained in one bottle of eye drops is too low to cause toxic reactions even after accidental ingestion. After topical application of an excessive dose, the eye should be rinsed with clean (tap) water at room temperature.

Interaction:

There were no special studies on drug interaction. Since the maximum concentration of levofloxacin in plasma after topical application in the eye is at least 1000 times lower than after taking standard doses orally, interaction with other drugs characteristic of systemic use is most likely clinically insignificant.

Special instructions:

The drug can not be administered subconjunctivally and into the anterior chamber of the eye.

The drug should not be used while wearing hydrophilic (soft) contact lenses in connection with the presence in it of the preservative benzalkonium chloride, which can be absorbed by contact lenses and have an adverse effect on the tissues of the eye, and also cause a change in the color of the contact lenses.

To avoid contamination of the tip of the dropper and solution, when instilled, do not touch eyelids and tissues around the eyes.

With long-term treatment with levofloxacin (as with other antibiotics), excessive growth of insensitive microorganisms, including fungal flora, is possible.

In case of worsening of the course of the disease or lack of improvement with the use of levofloxacin, it is necessary to cancel levofloxacin therapy and switch to therapy with antibacterial drugs of other groups, with an advanced ophthalmological examination including biomicroscopy and a fluorescein test. Information on the efficacy and safety of levofloxacin in the therapy of corneal ulcers is not available.

In the course of clinical studies, the formation of corneal precipitates was not observed.

Effect on the ability to drive transp. cf. and fur:

The drug does not have a significant effect on the ability to drive vehicles, mechanisms. Immediately after instillation, temporary blurring of vision is possible. It is not recommended to drive vehicles and engage in other potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions, until the clarity of visual perception is restored.

Form release / dosage:

Eye drops 0.5%.

Packaging:

5 ml per bottle with a dropper of low-density polyethylene and a lid with a control of the first opening or a flask-dropper made of high-density polyethylene, complete with a cap screwed and stopper-dropper.

1 bottle with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

After opening the bottle - 1 month.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LP-004314

Date of registration:01.05.2017

Expiration Date:01.05.2022

The owner of the registration certificate:GROTEKS, LLC GROTEKS, LLC Russia

Manufacturer: & nbsp

GROTEKS, LLC Russia

Information update date: & nbsp22.06.2017

Illustrated instructions

Instructions

Levofloxacin-SOLOfarm (Levofloxacin-SOLOfarm)