LEVOXAN

PATIENT INFORMATION LEAFLET

LEVOXAN

TRADE NAME
Levoxan

INTERNATIONAL NONPROPRIETARY NAME
Levofloxacin

PHARMACEUTICAL FORM
Film-coated tablets.
Description: light peach coloured, oblong, scored on one side film-coated tablets.

COMPOSITION
Film-coated tablet contains
Active ingredient: levofloxacin (as levofloxacin hemihydrate) 500 mg.
Excipients: microcrystalline cellulose, crospovidone, hydroxypropylmethylcellulose, magnesium stearate, silica colloidal anhydrous.
Film coating composition: Opadry® II yellow 85G32281 (polyvinyl alcohol, talc, titanium dioxide, polyethyl glycol, lecithin, yellow iron oxide, red iron oxide).

ATCCODE                               J01MA12

PHARMACOTHERAPEUTIC GROUP
Quinolone antibacterial drugs.

PHARMACOLOGICAL PROPERTIES PHARMACODYNAMICS
Levoxan is a fluoroquinolone antimicrobial drug with broad spectrum of action. Levofloxacin, the active substance of the drug, is an optically active levorotatory isomer of ofloxacin - L-ofloxacin. Levofloxacin blocks DNA gyrase (topoisomerase II) and topoisomerase IV, interrupts cross-linking of DNA breaks, inhibits DNA synthesis, causes deep morphological changes in the cytoplasm, cell wall and membranes.
Levofloxacin is active against most strains of microorganisms both in vitro and in vivo:

  1. aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp. groups С and G (including Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans);
  2. aerobic gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp., Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (including Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis, Morganella morganii, Neisseria gonnorrhoeae, Neisseria meningitidis, Pasteurella spp. (including Pasteurella conis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa), Salmonella spp., Serratia spp. (Serratia marcescens);
  3. anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veilonella spp.;
  4. other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

PHARMACOKINETICS
Absorption
A 500 mg single dose results in the maximum plasma concentration of 5.2-6.9 μg/ml achieved in 1.3 hour.
After oral administration, levofloxacin is rapidly and almost completely absorbed from the GIT. Food intake has little effect on the rate and completeness of absorption.
Pharmacokinetics of levofloxacin is linear and predictable at a single and repeated administration of the drug. Levofloxacin plasma concentrations profile after I.V. administration is similar to that after ingestion of a tablet, so oral and I.V. methods of administration can be considered interchangeable.
Distribution
Plasma protein binding is 30-40%.
The drug penetrates well into organs and tissues: lungs, bronchial mucosa, phlegm, urinary system organs, genitalia, bone tissue, cerebrospinal fluid, prostate, polymorphonuclear leucocytes and alveolar macrophages.
Metabolism
A small amount of levofloxacin is metabolized in liver.
Elimination
Half-life after 500 mg single administration is 6-8 hours.
The drug is eliminated predominantly by glomerular filtration and tubular secretion in kidneys.
About 87% of the dose is eliminated unchanged with urine in 48 hours. Less than 4% is found in feces for 72 hours.
Pharmacokinetics in special clinical cases
Pharmacokinetics of levofloxacin does not depend on gender and age of the patient. Elderly people (from 66 to 80 years of age) demonstrate a slightly prolonged half-life; however no dose adjustment is needed. Patients with renal dysfunction (creatinine clearance less than 50 ml/min) need dose adjustment to avoid a cumulative effect. Levofloxacin is not eliminated by hemodialysis and continuous ambulatory peritoneal dialysis, so additional doses are not needed at these procedures. Patients with liver dysfunction are not expected to show alterations in pharmacokinetics of levofloxacin, as its liver metabolism is insignificant. Pharmacokinetics of levofloxacin in children has not been studied.

THERAPEUTIC INDICATIONS
Infectious and inflammatory diseases, caused by susceptible microorganisms:

  1. ENT infections: acute sinusitis;
  2. lower respiratory tract infections: acute exacerbations of chronic bronchitis, community-acquired pneumonia;
  3. complicated renal and urinary tract infections, including pyelonephritis;
  4. uncomplicated urinary tract infections;
  5. chronic prostatitis;
  6. infections of skin and soft tissues;
  7. septicemia/bacteremia, related to the above conditions.

DOSAGE AND ADMINISTRATION
Levoxan is taken orally 1-2 times a day regardless of food intake, without chewing and drinking plenty of fluids. Dosage depends on the character and severity of the disease, as well as on the susceptibility of the presumed causative agent.
Patients with normal or moderately reduced renal function (creatinine clearance > 50 ml/min) are recommended the following dosage regimen:

  1. acute sinusitis: 500 mg once daily, treatment course of 10-14 days;
  2. acute exacerbations of chronic bronchitis: 500 mg once daily, treatment course of 7 days;
  3. community-acquired pneumonia: 500 mg once daily, treatment course of 7-14 days;
  4. complicated urinary tract infections and acute pyelonephritis: 250 mg once daily, treatment course of 10 days;
  5. uncomplicated urinary tract infections: 250 mg once daily, treatment course of 3 days;
  6. chronic prostatitis: 500 mg once daily, treatment course of 28 days;
  7. uncomplicated infections of skin and soft tissues: 500 mg once daily, treatment course of 7-10 days.

Patients with renal dysfunction need dose regimen adjustment based on creatinine clearance. The drug is prescribed

 

Creatinine clearance

Dosage regimen

250 mg/24 hours

500 mg/24 hours

500 mg/12 hours

first dose: 250 mg

first dose: 500 mg

first dose: 500 mg

50-20 ml/min

then: 125 mg/24 hour

then: 250 mg/24 hour

then: 250 mg/12 hour

19-10 ml/min

then: 125 mg/48 hour

then: 125 mg/24 hour

then: 125 mg/12 hour

< 10 ml/min (including hemodialysis and CAPD)

then: 125 mg/48 hour

then: 125 mg/24 hour

then: 125 mg/24 hour

No additional doses are required after haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
No special dose adjustment is needed in case of liver dysfunction, as Levoxan metabolizes in liver insignificantly.

CONTRAINDICATIONS

  1. hypersensitivity to the components of the drug or to other quinolones;
  2. epilepsy;
  3. tendon lesions related to administration of quinolones in the medical history;
  4. pregnancy and lactation period;
  5. infancy and adolescence under 18 years of age.

The drug should be administered with caution in elderly patients due to high probability of associated reduction in renal function, with deficit of glucose-6-phosphate dehydrogenase.

SIDE EFFECTS
Determination of the frequency of adverse effects: common (≥ 1/100 to < 1/10), uncommon (≥1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency is unknown (frequency cannot be estimated with the available data).
Digestive system: common - nausea, diarrhea; uncommon – loss of appetite, vomiting, abdominal pain, digestive disorders; rare – bloody diarrhea.
Metabolism: very rare – hypoglycemia; in separate cases – exacerbation of existing porphyria.
CNS and peripheral nervous system: uncommon - headache, dizziness, stiffness, somnolence; rare – paresthesias in hands, tremor, anxiety, fear, convulsive attacks and mental confusion; very rare – vision and hearing disturbances, taste and smell perversion, reduction in tactile sensation, hallucination- and depression-like psychotic reactions, motor disturbance (including at walking).
Cardiovascular system: rare - tachycardia, decrease in blood pressure; very rare – vascular collapse.
Musculoskeletal system: rare – tendon lesions, articular and muscular pain.
Urinary system: rare – serum creatinine increase; very rare – renal function impairment up to development of acute renal deficiency.
Hematopoietic system: uncommon - eosinophilia, leukopenia; rare - neutropenia, thrombocytopenia; very rare – expressed agranulocytosis (associated with a persistent or recurrent increase in body temperature, tonsils inflammation and persistent deterioration of the general state with possible development of severe infections).
Allergic reactions: uncommon - pruritus and skin redness; rare – anaphylactic and anaphylactoid reactions (urticaria, bronchospasm and possible severe suffocation, on rare occasions – facial and laryngeal oedema).
Dermatologic reactions: rare - photosensibilization.

PARTICULARINDICATIONS
Exercise caution prescribing Levoxan to:

  1. elderly patients (due to high probability of existence of associated decrease in renal function and increased risk of tendon rupture);
  2. patients with previous brain injury, including insult or severe brain trauma (due to increase in convulsive readiness);
  3. patients with diabetes mellitus (possible development of hypoglycemia);
  4. patients with renal dysfunction (the drug is prescribed with caution concomitantly with the drugs blocking tubular secretion).

The patients should avoid exposure to sunlight or UV-irradiation to avoid development of photosensibilization.
In case of suspected pseudomembranous colitis Levoxan must be immediately withdrawn and respective treatment must be initiated. Administration of the drugs inhibiting intestinal motility is prohibited.
The alcohol use should be excluded during the treatment.

INFLUENCE ON ABILITY TO DRIVE AND OPERATE MECHANISMS
In the course of treatment patients should exercise caution when driving and engaging in other potentially dangerous activities requiring high attention focusing and speed of psychomotor reaction.

PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and lactation.

PEDIATRIC USE
The drug is contraindicated to children and adolescents under 18.

DRUG INTERACTIONS
The effect of Levoxan is significantly reduced when used concomitantly with sucralfate, antacids containing magnesium or aluminum, and ferrous salts.
Levofloxacin, as all quinolones can increase the ability of the drugs (nonsteroidal anti-inflammatory drugs, theophylline) to lower the threshold of convulsive readiness.
Elimination (renal clearance) of levofloxacin is slightly inhibited by cimetidine and probenecid, which has little clinical significance.
Concomitant use with vitamin K antagonists requires control of blood coagulation system. Levofloxacin leads to slight increase in plasma cyclosporine half-life.
Concomitant use with glucocorticosteroids increases risk of tendon rupture.

OVERDOSE
Symptoms: mental confusion, dizziness, mental disorders and epilepsy-like convulsive attacks, nausea, erosive lesions of mucous membranes.
Treatment: symptomatic treatment is performed. Levofloxacin is not eliminated by dialysis. No specific antidote is available.

PACKAGING
Film-coated tablets. 7 tablets in a blister.
1 blister with the enclosed leaflet in a carton box.

STORAGE CONDITIONS
Store in a protected from moisture place at temperature not exceeding 25°С. Keep out of reach of children!

SHELF LIFE
3 years from the manufacturing date. Do not use after expiry date.

SALES TERMS
Sold under prescription.

MANUFACTURER
LEVOXAN is a product and a trade mark of "Sanolife”, Great Britain.
Manufactured by
"WORLD MEDICINE İLAÇ SAN. VE TİC. А.Ş.", TURKEY