LEVOFLOXACIN INFUSION SOLUTION 0.5 %
Solutio Levofloxacini 0.5% pro infisio
International nonproprietary name (INN)
Antibacterial agent of system usage. Fluoroquinolones.
Active substance – levofloxacin hemohydrate (calculated on levofloxacin basis) 5 g
Auxiliary substances – sodium chloride 9 g, disodium ethylene diamine-N,N,N´,N´-tetraacetic acid 2-salt solution.
Antibacterial agent of fluoroquinolones, sinistrorotatory isomer of ofloxacin. It is of vast gamma of antibacterial (bactericide) activity.
It inhibits bacterial topoisomerase IV and DNA-girase,enzymes responsible for replication, transcription, repair and recombination of bacterial DNA. It provokes deep morphological modficiations in cytoplasm, bacterial cell wall and membrane. The drug is active against the majority of bacterial cultures:
- anaerobic gram-positive bacteria: Corynebacterium diphtheriae, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Viridans group streptococc (penicillin sensitive and penicillin resistant cultures);
- anaerobic gram-negative bacteria: Acinetobacter spp (inclusive: Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter anitratus), Actinobacilus actinomycetemcomitans, Citrobacter freundii, Citrobacter diversus, Eikenella corrodens, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter sakazakii, Escherichia coli, Gardenella vaginalis, Haemophilus ducrey, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Legionella pneumoniae, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitides, Pasteurella dagmatis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Providencia retgeri, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella spp., Serratia spp.( яSerratia marcescens inclusive);
- anaerobic bacteria: Bacteroides fragillis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus, Propionibacterium spp., Veillonella spp.;
- other bacteria: Bartonellaspp. Bordetella pertussis, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis,Legionellapneumophila, Mycoplasma pneumoniae.
Linear pattern of levofloxacin pharmacokinetics. After single i.v.injection of 500 mg (60 min.infusion) Cmax. is 6.2±1.0 mg/ml. Stable plasma concentration is achieved in 48h. after 500 mg/day dose and is 6.4±0.8 mg/ml. Average distribution volume is 74-112 l after single and multiple doses 500 and 750 mg. it is widely spread in organs and tissues, easily penetrated to lungs (lung concentration is 2-3 times of plasma concentration), bronchus mucous tunic and sputum, urogenital system, serebrospinal fluid. Plasma protein binding is 24-38 % (mainly with albumin). Stereichemical stability in plasma and urine, it is not transformed into its enantiomer, D-oxifloxacin. It is practically not metabolized. About 5% is found in urine as metabolites (desmethyl, nitric oxide) of insignificant pharmacological activity. It is mainly renal excreted unmodified: 87 % of the dose within 48 h., and a little feces excreted: less than 4% within 72 h. Т1/2 after i.v.injection is 6-7 h. generalclearanceis144-226 ml/min, renal 96-142 ml/min. Excretionisachievedbyglomerularandcanalesofsecretion. Levofloxacin pharmacokinetics does not depend on sex and age of the patient. Inelderlypatients (fromm 66 to 80) Экстрекция осуществляется путем клубочковой и канальцевой секреции. Фармакокинетика левофлоксацина не зависит от пола и возраста пациента. У пожилых людей (в возрасте от 66 до 80 лет) Т1/2isslightlyprolonged to 7.6 h., stilldosecorrectionisnotrequired. In patients with renal failure (creatinine clearance less 50 ml/min) dose correction is required to avoid cumulative effect. Hemodialysis and long outpatient peritoneal dialysis does not excrete levofloxacin, hence additional doses are not required during the procedure. In patients with hepatic failure levoflaxicin pharmacokinetics is not altered as its hepatic metabolism is insignificant. In children levoflaxicin pharmacokinetics has not been studied.
Lung therapy, moderate and heavy infections caused by bacterila culture sensitivity to levofloxacin, acute sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarhalis
Administration and dosage
i.v.drop injection of the drug, slowly 250-750 mg every 24 h. (250-500 mg within 60 min., 750 mg – within 90 min.). Further eventual change for oral intake in the same dose. Course of treatment is subject to indications and sensitivity to pathogen. Followstrictlyrecommendeddoses. Course of treatment is 2-3 days after normalization of the temperature. It is prohibited to cancel without doctor’s advise or before the fixed time.
Pneumonia: i.v. 500 mg 1-2 time a day for 7-14 days.
Non-complicated infections of urinary tracts: i.v. 250 mg 1 time a day for 3 days.
Heavy renal and urinary infections i.v. dose and the period may be prolonged.
Sin and soft tissue infection: i.v. 500 mg 2 times a day for 7-1 4 days.
Severe pneumonia, caused by pneumococcus and in hospital infection caused by pathogen Pseudomonas aeruginosa the drug may be insufficient and combined therapy is required.
In patients with renal failure correction dose is required subject to clearance of creatinine. Thepatternis:
clearance of creatinine 50-20 ml/min: the first day common dose (recommended in patients with regular clearance of creatinine), from the second day decrease twice the dose;
clearance of creatinine 19-10 ml/min the first day common dose (recommended in patients with regular clearance of creatinine), from the second day decrease 4 times the dose;
clearance of creatinine less 10 ml/min (hemodialysis and long outpatient peritoneal dialysis inclusive) the first day common dose (recommended in patients with regular clearance of creatinine). If the dose is NMT 500mg/day, from the second day decrease 4 times the dose. In patients with the dose 500 - 1000 mg/day, from the second day decrease 8 times the dose.
Infusion solution of the drug is compatible with the following infusion solutions: salt solution, 5% glucose solution. 2.5% Ringer's solution with dextrose, combined solutions for parenteral feeding (aminoacids, carbones, electrolytes). Do not mix drug infusion solution with heparin or basic reactive solutions (as sodium bicarbonate).
Driving and operating dangerous mechanisms: for the period of treatment avoid driving and operating dangerous mechanisms due to eventual vertigo, sleepiness, stiffness and eye disorder that may cause lower reaction and concentration.
Allergic reaction: sometimes itch and redness, rare anaphylactic and anaphylactoid reaction (symptoms like utricaria, face edema, v ery rare spontaneous drop of AP and shock, in single cases Stevens-Johnson syndrome, toxic epidermal necrosis (Lyell's syndrome) and exudative multiforma erythema;
Local reaction: pain and inflammation in the palce of i.v.injction, dorsum and breast pain, hyperhidrosis;
Nervous system: sometimes headache, vertigo, fatigue, gustatory disorder, rare paresthesia of hands, tremor, anxiety, fear, convulsion attack, mental confusion, very rare visual and ear disorder, taste and olfaction disorder, lower thigmesthesia, concentration disorder, psychotic reaction as hallucination and depression, coordination disorder (walking inlusive);
Digestive system: often nauseam, diarrhea, sometimes loss of appetite, vomit, stomach pain, digestion disorder, rare dry mouth, gastrointestinal hemorrhage, higher level of serum bilirubine, very rare blood diarrhea (very rare it may manifest intestinal inflammation or pseudomembranous colitis, hepatic failure (hepatitis, cholelithiasis).tonsillitis;
Hemopoietic organs: sometimes eosinophilia, leucopenia, rare neutropenia, thrombocytopenia (tendency to hemorrhage or bleeding), very rare marked granulocytopenia (accompanied by persistent or recurrent higher temperature, tonsillitis and persistent regression of health), in single cases hemolytic anemia, pancytopenia;
Cardiovascular system: rare tachycardia, hypotensia, very rare increased QT interval in cardiogram, vascular collapse, ventricle flutter/fibrillation;
Musculoskeletal system: rare tendon injury (tendonitis inclusive), articulation and muscle pain, very rare Achilles tendon rupture (may be of bilateral nature and is developed in 48 h. after treatment), muscle fatigue (very important in patients with myasthenia), in singe cases rabdomyolisis;
Urogenital system: sometimes vaginitis, very rare regression of renal function and acute renal failure (e.g. caused by allergic reaction interstitial nephritis);
Other sometimes asthenia, very rare hypoglycemia, fever, allergic pneumonitis, vasculitis;
Analytical parameters: sometimes higher activity of ALT, AST, higher level of creatine on blood serum, rare increased LDH, glucose content decrease or increase.
Hypersensitivity to levofloxacin or other quinolones, epilepsy, tendon injury due to quinolone intake in anamnesis, children under 18.
Administer with care in patients with previous cerebral injuries (stroke or severe trauma) due to eventual convulsions.
In patients with diabetes receiving concurrently oral hypoglycemic agents (insulin or glibenclamid) levofloxicin may provoke hypoglycemia.
To eliminate photosensitivity in patients it is recommended to avoid sun or UV radiation (as long staying under the sun or solarium), in case of phototoxic effect (skin eruption) cancel the drug.
In patients with glucose-6-phosphatdehydrogenase deficiency possible erythrolysis.
In case of persistent severe diarrhea with or without blood consult a doctor. Diarrhea may cause enteroclotitis, generated by antiobiotic therapy. If suspected pseudomembranous colitis immediately cancel the drug and start respective therapy. In this case do not administer medicines depressing intestinal motility.
In elderly patients possible tendonitis (Achilles tendon) and its rupture. If suspected tendonitis, cancel the drug and start treatment of the injured tendon providing immobilization.
Interaction with other drugs
In combined therapy of phenbuphen and simila NSAID, teophillin, the drug may increase the threshold of convulsion.
Sucraphalt, iron and magnesium salts or aluminum-containing antacidic agents significantly decrease levofloxacin action (interval between intake of drugs is NLT 2 h.).
Concurrent administration of varpharin increases PT and hemorrhage risk (careful monitoring of MNO, PT and other parameters of coagulation and monitoring of possible bleeding signs).
Levofloxacin excretion is inhibited insignificantly by cimetidineprobenecid. Levofloxacin increases slightly T1/2 of cyclosporine from blood plasma.
Glycocorticoids increase the risk of tendon rupture (in particular in elderly patients).
Alcohol may increase side effects of CNS (vertigo, stupor, sleepiness).
In patients with diabetes receiving hypoglycomioc agents or insulin, against levofloxacin possible hypo- and hyperglycemic conditions (careful monitoring of glucose level in blood).
Glass bottle for blood/transfusion/infusion agents 100m. the bottle and the instruction for usage in individual pack of cardboard. Package for hospitals: 56 bottles with the respective number of instructions for usage in cardboard box.