Levofloxacin

566 7 minutes read

Active material: Levofloxacin
When ATH: J01MA12
CCF: Fluoroquinolone antibacterial drug
ICD-10 codes (testimony): J01, J15, J20, J32, J42, L01, L02, L03, L08.0, N10, N11, N30, N34, N41
At KFU: 06.17.02.01
Manufacturer: LEK d.d. (Slovenia)

Pharmaceutical form, composition and packaging

Pills, Film-coated orange-pink, bright, octagonal, lenticular, with Valium on both sides.

	1 tab.
levofloxacin (in the form of hemihydrate)	250 mg

Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch, talc, Colloidal anhydrous silica, Croscarmellose sodium, glyceryl dibegenat.

The composition of the shell: gipromelloza, giproloza, macrogol 6000, iron oxide yellow, iron oxide red, Titanium dioxide, talc.

5 PC. – blisters (1) – packs cardboard.
5 PC. – blisters (2) – packs cardboard.
5 PC. – blisters (3) – packs cardboard.
5 PC. – blisters (5) – packs cardboard.
7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (3) – packs cardboard.
7 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.

Pills, Film-coated orange-pink, bright, octagonal, lenticular, with Valium on one side.

	1 tab.
levofloxacin (in the form of hemihydrate)	500 mg

Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch, talc, Colloidal anhydrous silica, Croscarmellose sodium, glyceryl dibegenat.

The composition of the shell: gipromelloza, giproloza, macrogol 6000, iron oxide yellow, iron oxide red, Titanium dioxide, talc.

Pharmacological action

Fluoroquinolone antibacterial drug. It has bactericidal activity. Does DNK-girazu and topoisomerase IV, suppressing DNA synthesis.

It is active against Aerobic gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus (strains, sensitive to Methicillin), Staphylococcus haemolyticus (strains, sensitive to Methicillin), Staphylococcus saprophyticus, Streptococcus Group c and G, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes; Aerobic gram-negative microorganisms: Acinetobacter baumannii, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Pasteurella multocida, Proteus is wonderful, Proteus vulgaris, Rettgeri Providence, Providence stuartii, Pseudomonas aeruginosa, Serratia wilting; anaerobes: Bacteroides fragilis, Clostridium perfringens, Peptostreptococcus spp.; other microorganisms: Chlamydia pneumoniae, Chlamydia psittaci, Legionella pneumophila, Mycoplasma pneumoniae.

C drug intermediate susceptible aerobic gram-positive microorganisms: Staphylococcus haemolyticus (methicillin-resistant strains); Aerobic gram-negative microorganisms: Burkholderia cepacia; anaerobic microorganisms: Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides vulgatus, Clostridium difficile.

By levofloksacinu insensitive Staphylococcus aureus (methicillin-resistant strains).

Pharmacokinetics

Absorption

The ingestion of levofloxacin quickly and almost completely absorbed from the digestive tract. Bioavailability is approximately 100%. C_max in plasma achieved within 1 no. Eating virtually no effect on absorption of levofloxacin.

Distribution

Plasma protein binding – 30-40%. Cumulation when taken in the dose of levofloxacin 500 mg 1 times/day practically no. A small accumulation of levofloxacin noted when taken in the dose of 500 mg 2 times / day. C_ss It reached within 3 days.

The ingestion dose of levofloxacin 500 mg C_max in the bronchial mucosa and bronhialnom secret achieved approximately 1 h after administration of the drug and make up 8.3 ug / ml 10.8 ug / ml, respectively; C_max in the lung tissue is achieved through 4-6 h after administration of the drug and is approximately 11.3 ug / ml. Concentration lungs exceeds the concentration in plasma. Levofloxacin bad penetrates into spinnomozgovu liquid.

The mean concentrations of drug in the urine through the 8-12 hours after administration of single doses 150 mg, 300 mg or 500 mg represent 44 mg / l, 91 mg/l and 200 mg/l, respectively.

Metabolism

Levofloxacin is metabolized very little with the formation of desmetil-levofloxacin and levofloxacin-N-oxide. These metabolites have less 5% dose, allocated through the kidneys.

Deduction

As a result, the intake of levofloxacin is eliminated from plasma relatively slowly (T_{1/2 –} 6-8 no). Drug excretion is mainly kidneys (> 85% of the administered dose).

Pharmacokinetics in special clinical situations

Violation of kidney function affect the farmakokinetiku levofloxacin. Excretion through the kidneys is reduced, together with decreased kidney function and, respectively, T_1/2 increases, as shown in the following table.

Clearance creatinine (ml / min)	T_1/2 (no)
< 20	35
20-40	27
50-80	9

Pharmacokinetics of levofloxacin in patients older has no significant differences, with the exception of those, which involve changes of creatinine clearance.

Testimony

Infection, caused by susceptible to malaria strains of microorganisms:

- Infections of upper respiratory tract (ostryi sinusitis);

- Infections of the lower respiratory tract (acute bronchitis, chronic bronchitis, community-acquired pneumonia);

-uncomplicated urinary tract infection and kidney failure;

— complicated urinary tract infection and kidney failure (including pyelonephritis);

- Prostatitis;

- Infections of the skin and soft tissues;

Dosage regimen

Tablets should be taken 1 or 2 times / day, regardless of the meal, not chewing and drinking plenty of fluids.

Dose and duration of treatment depend on the indications and the severity of the disease. When selecting dose tablet can be divided into parts by dividing the risk. Treatment with Fleksid^® should last at least another 48-72 hours after the disappearance of symptoms. The maximum duration of treatment no more than 14 days.

Dose for patients with normal renal function (CC > 50 ml / min)

Reading	Daily dose (Depending on the severity of the)	Duration of treatment
Ostryi sinusitis	500 mg 1 time / day	10-14 days
Exacerbation of chronic bronchitis	250-500 mg 1 time / day	7-10 days
Community-acquired pneumonia	500 mg 1 or 2 once a day	7-14 days
Uncomplicated urinary tract infections	250 mg 1 once a day	3 day
Complicated urinary tract infections (including pyelonephritis)	250 mg 1 once a day	7-10 days
Prostatitis	500 mg 1 once a day	14-28 days
Infections of the skin and soft tissues	250 mg 1 Once a day or 500 mg 1 or 2 once a day	7-14 days

Patients with impaired renal function (creatinine clearance < 50 ml / min) selection of individual doses needed.

Creatinine clearance	Doses Depending on the severity of the condition and Nosology
Creatinine clearance	The first dose 250 mg / 24 h	The first dose 500 mg / 24 h	The first dose 500 mg / 12 h
50-20 ml / min	then – 125 mg / 24 h	then – 250 mg / 24 h	then – 250 mg / 12 h
19-10 ml / min	then – 125 mg / 48 h	then – 125 mg / 24 h	then – 125 mg / 12 h
< 10 ml / min (including dialysis and NAPD)*	then – 125 mg / 48 h	then – 125 mg / 24 h	then – 125 mg / 24 h

* – after hemodialysis or continuous ambulatory peritoneal dialysis (NAPD) receive additional doses is not required.

At abnormal liver function does not require a special selection of doses, Since levofloxacin is not exposed to significant metabolism in liver.

Individual selection of doses for elderly patients not required (However, There is a need to control the creatinine clearance, tk. more likely concomitant decline of kidney function).

Side effect

Below listed side effects is classified as follows: very common (>10%), common (1-10%), unextended (0.1-1%), few (0.01-0.1%), very rare (<0.01%).

From the digestive system: common – nausea, diarrhea (incl. mixed with blood), increase in liver enzymes (GOLD, IS); unextended – decreased appetite, vomiting, abdominal pain, dyspepsia, giperʙiliruʙinemija; few – enterocolitis, psevdomembranoznыy colitis; very rare – gipoglikemiâ, hepatitis.

From the nervous system: unextended – headache, dizziness, sleep disturbance; few – paresthesia, tremor, anxiety, excitation, confusion, convulsions; very rare-hallucinations, ekstrapiramidnye violations and other violations of the coordination.

From the senses: very rare – visual impairment, hearing, olfactory, gustatory and tactile sensitivity.

Cardio-vascular system: few – tachycardia, hypotension; very rare – vascular collapse.

On the part of the musculoskeletal system: few – arthralgia, myalgia, Tendinitis; very rare – tendon rupture (eg, ahillovogo tendon), muscular weakness (is of particular importance for patients with myasthenia); in some cases – raʙdomioliz.

From the urinary system: unextended – giperkreatininemiя; very rare – interstitial nephritis, worsening of renal function until the acute renal failure.

Blood system and organs of Hematopoiesis: unextended – eozinofilija, leukopenia; few – neutropenia, thrombocytopenia; very rare – agranulocytosis; in some cases – gemoliticheskaya anemia, pancytopenia.

Allergic reactions: unextended – itch, skin rash; few – hives, bronchospasm, breathlessness; very rare – angioedema, hypotension, anaphylactic shock, hypersensitivity pneumonitis, photosensitivity; in some cases – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme.

Other: unextended – asthenia; very rare – fever, vasculitis.

Contraindications

- Epilepsy;

- Destruction of tendons, arising from previously conducted treatment with fluoroquinolones;

- Up to 18 years;

- Pregnancy;

- Lactation (breast-feeding);

-hypersensitivity to levofloksacinu or other hinolonam, and/or to other components of the drug.

Observe caution:

— appointment of levofloxacin combined with drugs, influencing tubuljarnuju secretion, such as Probenecid and cimetidine, especially when treating patients with the human kidney;

— in the treatment of patients with a predisposition to seizures and obstructed, during treatment fenbufenom and similar nonsteroidal anti-inflammatory drugs (NSAIDs) or drugs, that lower the threshold for seizures, such as, theophylline;

-in patients with latent or apparent violations activity of glucose-6-phosphate dehydrogenase in relation to risk of hemolytic reactions.

Pregnancy and lactation

The drug is contraindicated in pregnancy and during breastfeeding.

Cautions

Fleksid^® You must take for 2 hours before or after 2 h after administration of iron salts, Antacids and sukralfata, because there may be reducing its absorption. If necessary, the simultaneous application of sucralfate should take over 2 h after administration Fleksida^®.

Patients, at the same time taking vitamin k antagonists, There is a need to control the parameters of blood coagulability.

In rare cases,, observed during treatment hinolonami tendonitis, can sometimes lead to tearing of the ligaments, especially Achilles tendon. This side effect is manifested within 48 hours after the start of therapy. For the elderly and patients, taking corticosteroids, There is an increased risk of tendinitis. So levofloksacinom during treatment requires careful monitoring of such patients. If there is suspicion of the tendonitis (you need to inform patients about its symptoms), Welcome Fleksida^® must be stopped immediately and start appropriate treatment (eg, immobilization).

Diarrhea (especially in cases of severe, counter and/or mixed with blood) during or after taking Fleksida^® may be a symptom of a disease, caused by Clostridium difficile, the most severe of which is pseudomembranous colitis. If there is a suspicion of pseudomembranous colitis, Welcome Fleksida^® should cease immediately and hold the symptomatic treatment (eg, Vancomycin oral). In this state of preparations, inhibiting peristalsis, contraindicated.

For the treatment of nosocomial infections, caused by Pseudomonas aeruginosa require combination therapy.

During drug treatment Fleksid^® You must avoid direct solar and artificial UV radiation (solarium), to avoid fotosencibilization.

Effects on ability to drive vehicles and management mechanisms

Be careful when driving vehicles and other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: nausea, erosion of the mucous membranes of the DIGESTIVE TRACT, confusion, dizziness, loss of consciousness and seizures.

Treatment: symptomatic therapy, ECG monitoring. Hemodialysis nyeeffyektivyen. No specific antidote.

Drug Interactions

Iron salts, antacids, containing magnesium or aluminum, lower absorption of levofloxacin.

Sukralfat reduces bioavailability of levofloxacin.

No pharmacokinetic interactions between identified levofloksacinom and theophylline. But, If it is accompanied by the use of quinolones and theofillina and NSAIDS may decrease the threshold sudorojna preparedness.

In the presence of fenbufena levofloxacin concentration approximately 13% higher, than when used as monotherapy.

If it is accompanied by the use of levofloxacin T_1/2 Cyclosporine increases by 33%.

While admission of levofloxacin and vitamin k antagonists (warfarin), There has been an increased blood clotting parameters (prothrombin time) and/or bleeding.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.

Vladimir Andreevich Didenko

566 7 minutes read