Tavanic

Active material: Levofloxacin
When ATH: J01MA12
CCF: Fluoroquinolone antibacterial drug
ICD-10 codes (testimony): A15, A18, A40, A41, J01, J15, J42, K65.0, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, N10, N11, N15.1, N30, N34, N41
When CSF: 06.17.02.01
Manufacturer: Aventis Pharma Germany GmbH (Germany)

Pharmaceutical form, composition and packaging

Pills, coated pale yellowish-pink, oblong, lenticular, with dividing groove.

Excipients: krospovydon, methylhydroxypropylcellulose, microcrystalline cellulose, sodium fumarate, macrogol 8000, talc, Titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172).

3 PC. – packings Valium planimetric (1) – packs cardboard.
5 PC. – packings Valium planimetric (1) – packs cardboard.
7 PC. – packings Valium planimetric (1) – packs cardboard.
10 PC. – packings Valium planimetric (1) – packs cardboard.

Pills, coated pale yellowish-pink, oblong, lenticular, with dividing groove.

Excipients: krospovydon, methylhydroxypropylcellulose, microcrystalline cellulose, sodium fumarate, macrogol 8000, talc, Titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172).

5 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (1) – packs cardboard.

Solution for infusion clear, greenish yellow.

Excipients: sodium chloride, concentrated hydrochloric acid, Sodium hydroxide, water d / and.

100 ml – colorless glass vials (1) – packs cardboard.

Pharmacological action

Antimicrobial group of fluoroquinolones, levovrashtayushtiy ofloxacin isomer. It has a wide spectrum of antimicrobial action.

Levofloxacin blocks DNA gyrase (topoisomerase II) and topoisomerase IV, crosslinking violates supercoiling and DNA breaks, It inhibits DNA synthesis, It causes profound morphological alterations in the cytoplasm, cell wall and membranes.

Levofloxacin is active against most strains of microorganisms in conditions in vitro, as well as in vivo.

In vitro чSensitivity (BMD ≤ 2 mg / ml) Aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (incl. Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive / methicillin-sensitive strains moderately), Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (strains of methicillin-chuvstvitelnye), Staphylococcus spp. (CNS), Streptococcus spp. G and G (incl. 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 actinimycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (incl. Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (incl. Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella cattaralis (strains, produciruûŝie and neproduciruûŝie β-lactamase), Morganella morganii, Neisseria gonnorrhoeae (strains, produciruûŝie and neproduciruûŝie penicillinazu), Neisseria meningitidis, Pasteurella spp. (incl. Pasteurella Conis, Pasteurella dagmatis, Pasteurella multocida), Proteus is wonderful, Proteus vulgaris, providencia spp. (incl. Rettgeri Providence, Providence stuartii), Pseudomonas spp. (incl. Pseudomonas aeruginosa), Salmonella spp., Serratia spp. (Serratia wilting); 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 spp. (incl. Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Levofloxacin moderately active (IPC ≥ 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; anaerobes: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovaius, Prevotella spp., Porphyromonas spp.

By levofoloksatsinu resistant ( IPC ≥ 8 mg / l) Aerobic gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), Staphylococcus spp. (coagulase-negative strains of methicillin-resistant); Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans; other microorganisms: Mycobacterium avium.

Pharmacokinetics

Absorption

After oral levofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake has little effect on the rate and completeness of absorption.

When a single dose 500 mg C_max plasma levels achieved after 1.3 h and is 5.2-6.9 ug / ml. Bioavailability – 100%.

After the / 60-minute infusion at a dose of levofloxacin 500 mg in healthy volunteers the mean C_max in plasma was 6.2 ± 1.0 pg / ml, T_max – 1.0± 0.1. The pharmacokinetics of levofloxacin is linear and predictable with single and multiple doses of the drug. The plasma concentration profile of levofloxacin after i / v administration is similar to that when taking tablets. Therefore, oral and / in the routes of administration may be interchanged.

Distribution

Plasma protein binding – 30-40%.

Well into the organs and tissues: lungs, bronchial mucosa, sputum, organs of urinary system, genitals, bone, cerebrospinal fluid, prostate, polymorphonuclear leukocytes, alyveolyarnыe macrophages.

Average V_d Levofloxacin is from 89 to 112 l after single and repeated on / in a dose of 500 mg.

Metabolism

In the liver, a small part of levofloxacin is oxidized and / or deacetylated.

Deduction

After receiving a single dose of 500 T mg_1/2 is 6-8 no.

After a single on / in a dose of 500 mg T_1/2 – 6.4± 0.7.

Write mainly by the kidneys by glomerular filtration and tubular secretion.

Average final T_1/2 It is between 6 to 8 h after single and multiple administration.

About 87% the dose is excreted in the urine unchanged within 48 no. Less 4% It found in the feces during the period 72 no.

Pharmacokinetics in special clinical situations

In renal insufficiency, reduced clearance of the drug and its excretion by the kidneys is dependent on the degree of reduction QC.

Testimony

Infectious-inflammatory diseases of mild to moderate severity, caused by susceptible to malaria infections:

- Ostryi sinusitis (orally);

- Exacerbation of chronic bronchitis (orally);

- Infections of the skin and soft tissues (orally);

- In the complex treatment of drug-resistant tuberculosis (orally);

- Community-acquired pneumonia (for both dosage forms);

- Complicated infections of the urinary tract, including pyelonephritis (for both dosage forms);

- Uncomplicated urinary tract infections (for both dosage forms);

- Prostatitis (for both dosage forms);

- Septicemia / bacteremia, Related to the above indications (for both dosage forms);

- Intra-abdominal infections (for both dosage forms).

Dosage regimen

The drug is taken by mouth or injected in / on 250-500 mg 1-2 times / day.

Doses are determined by the nature and severity of the infection, as well as the sensitivity of the pathogen.

Patients with normal or mildly impaired renal function (CC >50 ml / min) The drug is recommended to appoint the following doses.

Sinusitis: inside 2 tab. 250 mg or 1 tab. 500 mg (500 mg levofloxacin) 1 time / day. A course of treatment – 10-14 days.

Exacerbation of chronic bronchitis: inwards 1 tab. 250 mg (250 mg levofloxacin), or 2 tab. 250 mg or 1 tab. 500 mg (500 mg levofloxacin) 1 time / day. A course of treatment – 7-10 days.

Community-acquired pneumonia: inwards 2 tab. 250 mg or 1 tab. 500 mg 1-2 times / day (500-1000 levofloxacin mg / day); or / – by 500 mg 1-2 times / day. A course of treatment – 7-14 days.

Uncomplicated urinary tract infections: inwards 1 tab. 250 mg (250 mg levofloxacin) 1 time / day; or / – 250 mg 1 time / day. A course of treatment – 3 day.

Complicated urinary tract infections (including pyelonephritis): inwards 1 tab. 250 mg (250 mg levofloxacin) 1 time / day; or / – 250 mg 1 time / day. In severe infections, the dose for i / v administration may be increased. A course of treatment – 7-10 days.

Prostatitis: inside 2 tab. 250 mg or 1 tab. 500 mg (500 mg levofloxacin) 1 time / day; or / – 500 mg 1 time / day. A course of treatment – 28 days.

Septicaemia / bacteraemia: inwards 2 tab. 250 mg or 1 tab. 500 mg 1-2 times / day (500-1000 levofloxacin mg / day); or / – by 500 mg 1-2 times / day. A course of treatment – 10-14 days.

Intra-abdominal infections: inside 2 tab. 250 mg or 1 tab. 500 mg (500 mg levofloxacin) 1 time / day; or / – by 500 mg 1 time / day. A course of treatment – 7-14 days in combination with antibacterial agents, acting on the anaerobic flora.

Infections of the skin and soft tissues: inwards 1 tab. 250 mg (250 mg levofloxacin) 1 time / day, or 2 tab. 250 mg or 1 tab. 500 mg (500 mg levofloxacin) 1-2 times / day (respectively 500-1000 levofloxacin mg per day). A course of treatment – 7-14 days.

IN complex therapy of drug-resistant tuberculosis Tavanic^® appointed interior 1-2 tab. 500 mg 1-2 times / day (500-1000 levofloxacin mg / day) to 3 Months.

Patients with impaired renal function required correction mode depending on the QC.

* continuous ambulatory peritoneal dialysis.

After hemodialysis or CAPD does not require administration of additional doses.

To elderly patients with normal renal function correction dosing regime is not required.

At abnormal liver function does not require a special selection of doses, poskolyku Tavanic^® metabolized in the liver in a very small extent.

Tablets should be taken with liquid, and drinking plenty of fluids (from 0.5 to 1 cup). In the selection of dose tablets can be broken along the separation groove. The drug can be taken before meals or at any time between meals.

Preparation Tavanic^® in the form of a solution is introduced into / in the drip slowly. The duration of administration in a dose of 500 mg (100 ml infusion solution / 500 mg levofloxacin) must be at least 60 m. The solution of the drug tavanic^® 500 mg / 100 ml is suitable for infusion solutions: 0.9% sodium chloride solution, 5% Dextrose, 2.5% Ringer's solution with dekstrozoй, Combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes). The solution of the drug can not be mixed with heparin or alkaline solutions with (eg, with a solution of sodium bicarbonate).

When the positive dynamics of the clinical condition of the patient within a few days of treatment, you can go on / in the drip to oral medication tavanic^® in the same dose.

Duration of treatment with / in the introduction, depending on the disease is not more 14 days.

As with other antibiotics, Tavanic treatment preparatom^® oral or / infusion is recommended to continue for at least 48-72 hours after the normalization of body temperature or after a reliable bacterial eradication.

If you miss a dose, as soon as possible to resume the reception and then continue to take Tavanic^® on the recommended scheme.

Patients should be cautioned against self-interruption or termination of therapy without the doctor's instructions.

Side effect

Determining the frequency of side effects:

Allergic reactions: sometimes – itchiness and redness of the skin; rarely – anaphylactic and anaphylactoid reactions (manifested by symptoms, as urticaria, bronchoconstriction and possible severe asphyxia); rarely – swelling of the skin and mucous membranes (eg, facial, larynx), sudden drop in blood pressure, shock, hypersensitivity pneumonitis, vasculitis; in some cases – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and exudative erythema multiforme.

Dermatological reactions: rarely – photosensitivity.

From the digestive system: often – nausea, diarrhea, increased ALT, IS; sometimes – loss of appetite, vomiting, stomach ache, digestive disorders; rarely – increase in bilirubin levels in the serum, diarrhea with blood (In very rare cases, it may be a sign of inflammation of the intestine or pseudomembranous colitis); rarely – hepatitis.

Metabolism: rarely – gipoglikemiâ (manifested by a sharp increase in appetite, nervoznostью, perspiration, tremor). Experience with other quinolones suggests, they can exacerbate existing porphyria, in some cases, this effect is not excluded when using the drug tavanic^®.

From the central and peripheral nervous system: sometimes – headache, dizziness and / or stiffness, drowsiness, sleep disorders; rarely – depression, anxiety, psychotic reactions such as hallucinations, paresthesias in kistyah Rukh, tremor, excited state, convulsions and confusion; rarely – visual and hearing impairment, disorders of smell and taste sensitivity, reduction of tactile sensitivity.

Cardio-vascular system: rarely – tachycardia, drop in blood pressure; rarely – vascular collapse; in some cases – QT prolongation.

On the part of the musculoskeletal system: rarely – tendon injury (including tendinitis), joint and muscle pain; rarely – tendon rupture, eg, Achilles tendon (It may be bilateral in nature and occur during 48 hours after initiation of treatment), muscular weakness (It is particularly important for patients, suffering from myasthenia gravis); in some cases – raʙdomioliz.

From the urinary system: rarely – increase in serum creatinine; rarely – worsening of renal function until the acute renal failure (eg, due to allergic reactions – interstitial nephritis).

From the hematopoietic system: sometimes – eozinofilija, leukopenia; rarely – neutropenia, thrombocytopenia (strengthening the tendency to hemorrhage, or bleeding); rarely – agranulocytosis and development of severe infections (accompanied by persistent or recurrent fever, inflammation of the tonsils and persistent malaise; in some cases – gemoliticheskaya anemia, pancytopenia.

Other: sometimes – asthenia; rarely – fever, hypersensitivity pneumonitis. Any antibiotic can cause changes in the microflora (bacteria and fungi), which is normally present in human.

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

Contraindications

- Epilepsy;

- Destruction of tendons, associated with the reception history quinolones;

- Childhood and adolescence up 18 years;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to levofloxacin or other quinolones.

FROM caution the drug should be used in elderly patients due to the high likelihood of concomitant decrease in renal function, in the definition, glucose-6-fosfatdegidrogenazы.

Pregnancy and lactation

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

Cautions

In appointing the drug elderly patients should be aware, that patients in this group often have impaired renal function.

During treatment with Tavanic^® possible development of an attack of convulsions in patients with previous brain damage (incl. stroke or severe brain injury). Seizure may be increased, and while the application fenbufen, similar to NSAIDs or theophylline.

In applying the drug in patients with diabetes should be borne in mind, Chto Tavanic^® can cause hypoglycemia.

In severe pneumonia, caused by Streptococcus pneumoniae, use of the drug tavanic^® may be inadequate. Hospital infections, caused by Pseudomonas aeruginosa, may require the use of combination therapy.

Despite, photosensitivity observed that the application of levofloxacin is very rare, to prevent its development patients should avoid exposure to the sun or UV radiation.

If you suspect pseudomembranous colitis should be lifted immediately tavanic^® and begin appropriate treatment. In such cases it is impossible to apply medicaments, suppress intestinal motility.

Elderly patients when using the drug tavanic^® increases the likelihood of developing tendinitis. In the application of the SCS, apparently, increases the risk of tendon rupture. If tendinitis is suspected, it should be lifted immediately tavanic^® and begin appropriate treatment, The state of peace in the affected area.

Precautions should be prescribed Tavanic^® odnovremenno with probenetsidom and tsimetidinom, that block tubular secretion; under their influence excretion of levofloxacin slightly slower. This interaction is virtually has no clinical significance and can be related primarily to patients with impaired renal function.

In an application tavanic^® and vitamin K antagonists necessary to monitor the blood coagulation.

During the antibiotic treatment can be observed changes in the microflora (bacteria, mushrooms), which is normally present in human. For this reason, the possibility of increasing the proliferation of bacteria and fungi, The antibiotic-resistant (secondary infection and superinfection), which in rare cases may require additional treatment.

Experience with other quinolones suggests, they can exacerbate porphyria. This effect is not excluded when using the drug tavanic^®.

When using quinolones in patients with deficiency of glucose-6-phosphate dehydrogenase possible hemolysis. Considering this, treatment Tavanikom^® these patients should be performed with caution.

It should adhere strictly to the recommended duration of administration, which should not be less than 60 min for 100 ml infusion solution. Experience with levofloxacin shows, during infusion may experience heart palpitations and transient drop in blood pressure. In rare cases, it may be a vascular collapse. If during infusion observed pronounced decrease in blood pressure, administration immediately cease.

Effects on ability to drive vehicles and management mechanisms

Tavanic^® can cause dizziness or stiffness, drowsiness, visual impairment, and reduce the ability to concentrate attention and speed of psychomotor reactions, which should be considered, if necessary, use of the drug in people, activities are related to driving, service and machinery, with work in an unstable position. Especially it concerns cases of drug interactions with alcohol.

Overdose

Symptoms: confusion, dizziness, impairment of consciousness and convulsive seizures by type of epileptic seizures, nausea, erosive lesions of the mucous membranes. The clinical and pharmacological studies in the application of doses of levofloxacin, exceeding the average therapeutic, QT prolongation was observed.

Treatment: symptomatic therapy. Levofloxacin is not displayed by dialysis. There is no specific antidote.

Error receiving one extra pill 250 mg Tavanic^® It has no negative effect.

Drug Interactions

Quinolones may enhance the ability of drugs (incl. fenbufen and similar NSAIDs, teofillina) lower the seizure threshold.

Action preparation Tavanic^® significantly reduced while the use of sucralfate, magnesium- or aluminum-containing antacids, as well as salts of iron (the interval between doses tavanic^® and these medicines should be at least 2 no). With calcium carbonate, the interaction is not revealed.

With simultaneous use of vitamin K antagonists requires monitoring of blood coagulation.

Deduction (renal clearance) levofloxacin slightly slower under the influence of cimetidine and probenecid, that almost no clinical significance.

Tavanic^® It causes a slight increase in T_1/2 Cyclosporin blood plasma.

Simultaneous treatment with corticosteroids increases the risk of tendon rupture.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

Drug in tablet form, coated, Store in a dry place at temperatures no higher than 25 ° C. Shelf life – 5 years. Do not use the medication after the expiration date, on the package.

A preparation in the form of a solution for injection should be stored in dry, dark place at a temperature no higher than 25 ° C. Shelf life – 3 year. When room lighting solution can be stored without skyshot no more 3 days.

The drug should be stored out of reach of children.