Remoflox ® Neo – infusion solution

INSTRUCTIONS FOR MEDICAL USE

REMOFLOKS® NEO

Trade name of the drug: Remoflox® Neo

Active substance (INN): Levofloxacin hemihydrate.

Dosage form: solution for infusion.

Contents:

100 ml of the solution contains:

active substance: Levofloxacin hemihydrate – 500 mg.

Excipients: Sodium chloride – 900 mg, hydrochloric acid (for optimal pH level), water for injections up to 100 ml.

Description: Light yellow or yellowish-green transparent solution.

Pharmacotherapeutic group: Antibacterial synthetic drug (group of fluoroquinolones).

ATX code: J01MA12

Pharmacological properties

Pharmacodynamics

It is an antimicrobial agent of the group of fluoroquinolones, left-handed isomer ofloxacin. It has a wide spectrum of antimicrobial activity.

The drug blocks DNA-enzyme (topoisomerase II) and topoisomerase IV, breaks superspiralization and cross-linking of DNA breaks, inhibits DNA synthesis, causes deep morphological changes in cytoplasm, cell wall and membranes.

The drug is active against most strains of microorganisms, both in vitro and in vivo.

In vitro sensitive (MAC ≤ 2 mg/ml) aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (including Enterococcus faecalis), Listeriamono cytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive/methicillin-moderately sensitive strains), Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus spp. (CNS), Streptococcus spp. group C and G (including Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus viridans (penicillin-sensitive/resistant strains); aerobic gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp, Actinobacillus actinimycetem comitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (including 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 cattaralis (β-lactamase producing and non-producing strains), Morganella morganii, Neisseria gonnorrhoeae (penicillinase producing and non-producing strains), Neisseria meningitidis, Pasteurella spp. (including Pasteurella conis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (incl. Pseudomonas aeruginosa), Salmonella spp. (Serratia marcescens); anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterum spp, Veilonella spp.; other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

The drug is moderately active (MPC≥4 mg/l) against aerobic Gram-positive microorganisms: Corynebacterium urealiticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains); aerobic Gram-negative microorganisms: Burkholderia cepacia, Campilobacter jejuni, Campilobacter coli; anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgaris, Bacteroides ovaius, Prevotella spp. , Porphyromonas spp.

The following aerobic gram-positive microorganisms are resistant to the drug (MPC ≥ 8 mg/l): Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), Staphylococcus spp. (coagulase-negative methicillin-resistant strains); aerobic gram-negative microorganisms: Alcaligenes xylosoxidans; other microorganisms: Mycobacterium avium.

Pharmacokinetics

After 60-minutes infusion of 500 mg levofloxacin in vivo, mean Cmax in plasma is 6.2±1.0 µg/ml, Tmax is 1.0±0.1 h. Pharmacokinetics of the drug has a linear character and is predictable with single and multiple drug administration. Plasma concentration profile of levofloxacin after intravenous administration is similar to that of tablets. Therefore, oral and intravenous routes of administration may be considered interchangeable.

Distribution. Binding to plasma proteins is 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, urinary system organs, genitals, bone tissue, cerebrospinal fluid, prostate, polymorphonuclear leukocytes, alveolar macrophages. Mean Vd of levofloxacin is from 89 to 112 l after single and multiple intravenous administration at a dose of 500 mg.

Metabolism. In the liver a small part of levofloxacin is oxidized and/or deacetylated. Excretion. After a single 500 mg i.v. injection the T1/2 is 6.4±0.7 hours. It is eliminated mainly by the kidneys via glomerular filtration and tubular secretion. Mean final T1/2 is 6 to 8 hours after single and multiple doses. About 87% of the dose is excreted unchanged in the urine within 48 hours. Less than 4% is detected in the feces within 72 hours.

Pharmacokinetics in special clinical cases. In renal insufficiency the drug clearance and its excretion by the kidneys depend on the degree of creatinine clearance (CK) decrease.

Indications for use

The drug is used for treatment of bacterial infections in adults, if the causative agents of these infections are bacteria sensitive to levofloxacin:

  • infections of ENT organs (sinusitis, otitis media);
  • infections of the lower respiratory tract: exacerbation of chronic bronchitis, community-acquired pneumonia;
  • intra-abdominal infections;
  • Uncomplicated and complicated urinary tract infections (including pyelonephritis);
  • Genital infections (including urogenital chlamydia);
  • Acute and chronic bacterial prostatitis;
  • Skin and soft tissue infections (festering atheromas, abscesses, furuncles);
  • Septicemia associated with the above indications.

Directions for use and dosages

Before use, a sensitivity test should be performed. The solution should be used within 3 hours after vial perforation. The drug is administered by IV 1-2 times a day.

The dose depends on the type and severity of infection. Regarding dosing, the following recommendations should be followed for adult patients with normal renal function and creatinine clearance >50 ml/min:

IndicationsDaily dose, mgNumber of injections per day
Non-hospitalized pneumonia5001-2 (respectively, a daily dose of 500-1000 mg of levofloxacin)
Complicated urinary tract infections, including pyelonephritis  250 1
Chronic bacterial prostatitis5001
Skin and soft tissue infections500-10001-2 (respectively, a daily dose of 500-1000 mg of levofloxacin)
Comprehensive treatment of drug-resistant forms of tuberculosis  500-10001-2 (respectively, a daily dose of 500-1000 mg of levofloxacin) – Up to 3 months

According to the patient’s condition after a few days it is possible to switch from the initial IV administration of levofloxacin to oral administration with the same dosage.

Since levofloxacin is excreted mainly by the kidneys, the dose should be reduced for patients with impaired renal function.

Side effects

Allergic reactions: sometimes – itching and redness of the skin; rarely – anaphylactic and anaphylactoid reactions (manifested by symptoms such as urticaria, bronchospasm and possible severe choking); very rarely – edema of the skin and mucous membranes (e.g., in the face, throat), a sudden drop in BP, shock, allergic pneumonitis, vasculitis; in some cases – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and erythema exudative multiforme.

Dermatological reactions: very rare – photosensitization.

The digestive system: frequently – nausea, diarrhea, increased ALT, AST, sometimes – loss of appetite, vomiting, abdominal pain, indigestion, rarely – increased serum bilirubin, diarrhea with blood (in very rare cases it can be a sign of inflammation of the intestine or pseudomembranous colitis); very rare – hepatitis.

Metabolism: very rare – hypoglycemia (manifested by a sharp increase in appetite, nervousness, sweating, trembling). Experience of using other quinolones indicates that they can cause aggravation of existing porphyria; in some cases, such an effect is not excluded by the use of the drug.

CNS and peripheral nervous system: sometimes – headache, dizziness and/or stiffness, sleepiness, sleep disorders; rarely – depression, anxiety, psychotic reactions such as hallucinations, paresthesias in the hands, trembling, agitation, seizures and confusion; very rarely – visual and hearing disorders, disorders of taste sensitivity and smell, decreased tactile sensitivity.

Cardiovascular system: rare – tachycardia, decreased blood pressure, very rare – vascular collapse, in some cases – prolongation of QT interval.

Musculoskeletal system: rare – tendon involvement (including tendinitis), joint and muscle pain; very rare – tendon rupture, such as Achilles tendon (may be bilateral and appear within 48 hours after treatment start), muscle weakness (of particular importance for patients with asthenic bulbar palsy); rare – rhabdomyolysis.

Urinary system: rare – increase in serum creatinine level; very rare – deterioration of renal function up to acute renal failure (e.g., due to allergic reactions – interstitial nephritis).

Blood system: sometimes – eosinophilia, leukopenia, rarely – neutropenia, thrombocytopenia (increased tendency to hemorrhage or bleeding), very rare – agranulocytosis and the development of severe infections (accompanied by persistent or recurrent body temperature, tonsil inflammation and persistent worsening of the state; in some cases – hemolytic anemia, pancytopenia.

Others: sometimes – asthenia; very rarely – fever, allergic pneumonitis. Any antibacterial therapy can cause changes in microflora (bacteria and fungi) that are normally present in humans.

Local reactions: often – pain at the injection site, redness, phlebitis.

Contraindications

  • Epilepsy;
  • tendon lesions associated with a history of taking quinolones;
  • Children and adolescents under 18 years of age;
  • pregnancy;
  • lactation (breastfeeding);
  • hypersensitivity to levofloxacin or other quinolones.

The preparation should be used with caution in elderly patients because of high possibility of concomitant reduction of renal function and glucose-6-phosphate dehydrogenase deficiency.

Drug interactions

Quinolones may increase the ability of drugs (including phenbufen and similar NSAIDs, theophylline) to lower the threshold of seizure readiness.

Action of levofloxacin is significantly reduced when concomitant use with sucralfate, magnesium or aluminum containing antacids, as well as with salts of iron (interval between the intake of levofloxacin and these medicines should be at least 2 hours). No interaction has been shown with calcium carbonate.

When concomitant use of vitamin K antagonists it is necessary to monitor the blood coagulation system.

Excretion (renal clearance) of levofloxacin is slightly delayed under the influence of cimetidine and probenecid, which has almost no clinical significance.

The drug causes a slight increase in T1/2 of cyclosporine in blood plasma.

Concomitant use with GCS increases the risk of tendon rupture.

Special indications

When prescribing the drug to elderly patients it should be borne in mind that patients of this group often have impaired renal function.

During treatment, seizures may develop in patients with previous brain damage (including stroke or severe traumatic brain injury). Seizure activity may also increase with concomitant use of phenbufen, NSAIDs similar to it or theophylline. When using the drug in patients with diabetes mellitus it should be borne in mind that levofloxacin may cause hypoglycemia.

In severe pneumonia caused by pneumococcus, the use of the drug may be insufficient. Hospital infections caused by Pseudomonas aeruginosa may require combination therapy.

Although photosensitization is very rare with levofloxacin, patients should avoid sun exposure or UV-exposure to the sun to prevent its development.

If pseudomembranous colitis is suspected, the drug should be immediately withdrawn and appropriate treatment started. In such cases, do not use drugs that inhibit intestinal motility.

In elderly patients, the likelihood of tendinitis increases when using the drug. The use of GCS seems to increase the risk of tendon rupture. If tendinitis is suspected, levofloxacin should be immediately withdrawn and appropriate treatment should be initiated, ensuring a state of rest in the affected area.

Caution should be exercised when prescribing the drug simultaneously with probenecid and cimetidine, which block tubular secretion; levofloxacin excretion is slightly delayed under their effect. This interaction has practically no clinical significance and may concern primarily patients with impaired renal function.

At simultaneous use of levofloxacin and vitamin K antagonists it is necessary to control the state of the blood coagulation system.

During antibiotic therapy, changes of microflora (bacteria, fungi) may be observed, which is normally present in humans. For this reason, increased reproduction of bacteria and fungi resistant to the used antibacterial agent (secondary infection and superinfection) is possible, which in rare cases may require additional treatment.

Experience with other quinolones shows that they can cause exacerbation of porphyria. A similar effect is not excluded with levofloxacin.

When using quinolones in patients with glucose-6-phosphate dehydrogenase deficiency, hemolysis of erythrocytes is possible. Taking this into account, treatment with levofloxacin should be performed with extreme caution in this category of patients.

Recommended duration of infusion should be strictly adhered to, which should be at least 60 min for 100 ml of infusion solution. Experience of levofloxacin use shows that during infusion, increased heart rate and transient BP drop may be observed. In rare cases there may be vascular collapse. If a marked drop in BP is observed during the infusion, the administration should be stopped immediately.

Administration during pregnancy and lactation. The drug is contraindicated for use during pregnancy and lactation (breast-feeding).

Effect on the ability to drive motor transport and operate machinery. The drug may cause dizziness or stiffness, somnolence, visual disturbances and impair concentration ability and psychomotor reactions, which must be taken into account when using this drug in patients whose activities are related to driving vehicles, operating machines and mechanisms and working in unsteady positions. This especially refers to cases of interaction of the drug with alcohol.

Use only clear solution in an undamaged bottle!

Failure to observe the storage and transportation conditions may lead to micro-cracking of the vial, thereby increasing the risk of microbial contamination of the solution.

For single-use sampling only!

Do not freeze or heat!

Overdose

Symptoms: confusion, dizziness, impaired consciousness and seizure-like seizures, nausea, erosive lesions of the mucous membranes. In clinical and pharmacological studies when using levofloxacin in doses exceeding average therapeutic, prolongation of QT interval was observed.

Treatment: symptomatic therapy is carried out. Levofloxacin is not excreted by dialysis. There is no specific antidote.

Form of production

Infusion solution 500 mg/100 ml or 1000 mg/200 ml in 100 ml or 200 ml vials.

Storage conditions

Store in a dry, dark place at a temperature not exceeding 25°C. Keep out of the reach of children!

Shelf life

2 years. Do not use after the expiration date.

Conditions of dispensing from pharmacy

Released by a doctor’s prescription.

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