Zolev

Zolev is a systemic antibacterial drug from the fluoroquinolone category.

Indications Zoleva

It is used in the treatment of infections, the development of which is provoked by the activity of bacteria that are sensitive to drugs:

• pneumonia;
• acute sinusitis;
• chronic bronchitis in the acute phase;
• septicemia or bacteremia;
• infectious lesions affecting the urinary system (with or without complications) – for example, pyelonephritis;
• lesions of soft tissues and epidermis;
• prostatitis;
• infections in the intra-abdominal area.

Release form

The product is produced in tablet form, in the amount of 5 pieces, packed in a blister plate. There is 1 blister in a box.

Zole infusions

The infusion fluid is available in containers with a volume of 0.1 or 0.15 l. There is 1 such container inside the package.

Pharmacodynamics

Levofloxacin has a wide range of antibacterial therapeutic activity. The bactericidal effect develops through the suppression of the bacterial enzyme DNA gyrase, which belongs to the 2nd type of topoisomerases, by the active substance of the drug. Due to such suppression, the transition of bacterial DNA from relaxation to a supercoiled state becomes impossible, which helps prevent subsequent reproduction of pathogenic cells. The spectrum of the drug's effect includes gram-negative and -positive microbes with non-fermenting microorganisms.

The following bacteria are sensitive to the drug:

• gram-positive aerobes: enterococcus faecalis, Staphylococcus aureus methi-S, Streptococcus agalactiae, pyogenic streptococcus, and also coagulase-negative staphylococcus type methi-S (1), streptococci from categories C and G, as well as pneumococcus peni-I/S/R;
• Gram-negative aerobes: Acinetobacter baumannii, Enterobacter agglomerans, Citrobacter freundii, Eikenella corrodens, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Haemophilus influenzae ampi-S/R, and also Haemophilus parainfluenzae, Morgan's bacillus, Klebsiella pneumoniae, Proteus mirabilis, Moraxella catarrhalis β+/– and Proteus vulgaris. In addition, the list includes Pasteurella multocida, Providencia roettgerii and Providencia stuartii, Pseudomonas aeruginosa and Serratia marcescens;
• anaerobes: Bacteroides fragilis, Peptostreptococci and Clostridia perfringens;
• Others: Legionella pneumophila, ureaplasma, chlamydophila pneumoniae, mycoplasma pneumoniae, chlamydophila psittaci and helicobacter pylori.

The following have variable sensitivity:

• gram-positive aerobes: Staphylococcus aureus methi-R.;
• gram-negative aerobes: Burkholderia cepacia;
• anaerobes: the bacterium thetaiotaomicron, Bacteroides ovatus, Clostridium difficile and Bacteroides vulgaris.

Resistant to the action of Zoleva: gram-positive aerobes – Staphylococcus aureus methi-R, as well as coagulase-negative Staphylococcus aureus category methi-S (1).

Like other fluoroquinolones, levofloxacin has no effect on the activity of spirochetes.

Pharmacokinetics

Absorption.

When taken orally, levofloxacin is rapidly and almost completely absorbed, reaching peak plasma levels within 60 minutes of administration.

The absolute bioavailability index is almost 100%. The drug has linear pharmacokinetic characteristics when taken in therapeutic doses of 0.05-0.6 g. Food intake does not affect the degree of absorption.

Distribution processes.

Approximately 30-40% of the substance is synthesized with plasma protein. The accumulation of the drug with a single daily use of 0.5 g is not clinically significant, so it can be ignored. Insignificant accumulation of the substance with twice daily use of 0.5 g of the drug is also assumed. Stable distribution figures are noted after 3 days.

The Cmax level of the drug in the area of the bronchial mucosa and epithelial secretion after administration of a 0.5 g dose per os reached 8.3, and also 10.8 mcg/ml, respectively.

In the area of lung tissue, the achievement of Cmax of the drug after using a dosage of 0.5 g per os was noted after 4-6 hours, and this indicator was approximately 11.3 μg/ml. Pulmonary values of the drug were constantly higher than its plasma indicators.

Inside the bubbly liquid, the Cmax of Zolev when consuming 0.5 g 1-2 times a day reaches 4 and 6.7 mcg/ml, respectively.

Levofloxacin exhibits poor penetration into the CSF.

When taking the drug orally for 3 days (0.5 g dose, once per day), the average drug levels inside the prostate were 8.7, and also 8.2 and 2 mcg/g after 2, 6 and 24 hours. The average drug ratio inside the prostate/blood plasma was 1.84.

The average values of levofloxacin in urine during the period of 8-12 hours after administration of a single dose of 0.15, 0.3 or 0.5 g per os reached 44, 91 and 200 mcg/ml, respectively.

Exchange processes.

The metabolism of levofloxacin is extremely weak, its breakdown products are components of desmethyl-levofloxacin, as well as levofloxacin N-oxide. Such substances make up less than 5% of the drug dosage excreted in urine.

Excretion.

When taken orally, the process of plasma excretion of levofloxacin is quite slow (half-life is 6-8 hours). Excretion occurs mainly through the kidneys (more than 85% of the dose). No noticeable difference in the pharmacokinetics of the drug is observed when administered intravenously or orally.

Dosing and administration

Scheme of taking pills.

The medicine should be taken 1-2 times a day. The portion size is determined by the severity and type of infection. The duration of therapy is related to the course of the disease, but is a maximum of 2 weeks. It is recommended to continue the course for another 48-72 hours after the temperature returns to normal or the elimination of pathogenic bacteria is confirmed by microbiological studies.

The medicine is swallowed whole, without chewing, with liquid. It is taken without reference to food intake. Tablets of 0.5 and 0.75 g can be divided in half.

The following dosage regimen of Zolev should be followed for therapy in adults with healthy renal function (creatinine clearance >50 ml/minute):

• acute sinusitis - take 0.5 g of the drug once a day. Therapy lasts 10-14 days;
• chronic stage of bronchitis at the stage of exacerbation - a single dose of 0.25-0.5 g of the drug per day. Treatment continues for about 7-10 days;
• outpatient pneumonia - take 0.5-1 g of the substance 1-2 times a day for 1-2 weeks;
• infections affecting the urethra (without complications) – 1 dose per day of 0.25 g of the drug. Therapy continues for 3 days;
• prostatitis – 1-time use of 0.5 g of the drug per day. The treatment cycle should last 28 days;
• infections affecting the urethra (with complications - for example, pyelonephritis) - a single dose of 0.25 g of the drug per day. Therapy lasts 7-10 days;
• infections affecting the subcutaneous layer and epidermis - 1-2 times a day use of 0.5-1 g of the substance. Duration of the course - 7-14 days;
• bacteremia or septicemia - 0.5-1 g of the drug 1-2 times a day. Treatment period - 10-14 days;
• Infections developing in the intra-abdominal area* – 0.5 g of the drug once a day. The drug should be taken for 7-14 days.

*combination with antibiotics that affect anaerobes.

Portion sizes for people with impaired renal function – CC values are <50 ml/minute:

• the CC rate is within 50-20 ml/minute: in mild form of the disease, the 1st dose is 0.25 g, and the subsequent ones are 0.125 g (in 24 hours). In moderate form, the size of the 1st portion is 0.5 g, and the subsequent ones are 0.25 (in 24 hours). In severe form, the 1st portion is 0.5 g, and the subsequent ones are 0.25 g (in 12 hours);
• CC level within 19-10 ml/minute: mild pathology – 1st dose is 0.25 g, subsequent doses are 0.125 g (over 48 hours). Moderate – 1st dose is 0.5 g, subsequent doses are 0.125 g (over 24 hours). Severe – 1st dose is 0.5 g, subsequent doses are 0.125 g (over 12 hours);
• CC values <10 (also people on hemodialysis or CAPD): mild disease - 1st dose is 0.25 g, subsequent doses are 0.125 g (over 48 hours). Moderate and severe disease - 1st dose is 0.5 g, subsequent doses are 0.125 g (over 24 hours).

Using a medicinal solution.

The drug is administered 1-2 times a day, at a low rate. The portion size is determined taking into account the severity and type of the disease, as well as the sensitivity of the causative bacteria to the drug. After the initial use of the intravenous form of the drug, therapy can be continued using tablets (if this method is acceptable to the patient). Taking into account the bioequivalence of the oral and parenteral forms of the drug, it is permissible to use the same dosages.

The duration of the infusion used is at least half an hour (for a dose of 0.25 g) or 1 hour (for a dose of 0.5 g).

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Use Zoleva during pregnancy

Due to the lack of tests regarding the use of Zolev in humans, as well as the possibility of damage to articular cartilage under the influence of quinolones during the growth stage of a child's body, it is prohibited to use it during lactation or pregnancy. If pregnancy occurs while taking the drug, you must notify your doctor about it.

Contraindications

Main contraindications:

• the presence of intolerance to levofloxacin, other quinolones or other components of the drug;
• epileptic seizures;
• patients with complaints of the development of negative symptoms in the tendon area after previously taking quinolones.

Side effects Zoleva

The use of the medication may cause the development of some side effects:

• lesions of an infectious or invasive nature: fungal forms of infections (including Candida fungi), as well as the proliferation of other resistant microbes;
• disorders affecting the activity of lymph and blood flow: eosinophilia, hemolytic anemia, leukopenia, neutro-, thrombocyto- and pancytopenia, as well as agranulocytosis;
• immune disorders: symptoms of hypersensitivity, including anaphylaxis and anaphylactoid shock, Quincke's edema, as well as anaphylactic and anaphylactoid manifestations. Sometimes these symptoms may appear immediately after using the first portion;
• problems with the nutritional process and metabolism: hypoglycemia (especially in diabetics), anorexia, as well as hyperglycemia or hypoglycemic coma;
• mental disorders: agitation, feeling of nervousness, confusion, restlessness and anxiety, insomnia, psychotic disorders (including paranoia and hallucinations) and depression. In addition, nocturnal delirium and pathological dreams, as well as psychotic disorders accompanied by self-destructive actions (suicidal thoughts and suicide attempts);
• disorders of the nervous system function: drowsiness, dizziness, convulsions, headaches, paresthesia and tremor. In addition, weakening of tactile sensations, polyneuropathy of sensorimotor or sensory nature and dysgeusia, which may be accompanied by parosmia, ageusia and anosmia. The list also includes fainting, dyskinesia, increased intracranial pressure (benign), extrapyramidal disorders and other disorders of motor coordination (for example, when walking);
• lesions affecting the visual system: visual blurring or disturbance, transient loss of vision;
• problems with auditory function and the labyrinth: hearing impairment, vertigo, hearing loss and tinnitus;
• cardiac disorders: palpitations, tachycardia and ventricular tachycardia, which can cause cardiac arrest. In addition, ventricular arrhythmia and torsades de pointes occur (often in individuals with a risk of prolongation of the QT interval), and prolongation of the QT interval is also noted on the ECG;
• vascular lesions: allergic vasculitis and decreased blood pressure;
• disorders of mediastinal or respiratory function, as well as the activity of the sternum organs: bronchospasm, dyspnea and pneumonitis of allergic origin;
• digestive disorders: loss of appetite, diarrhea, abdominal pain, stomatitis, vomiting, and in addition symptoms of dyspepsia, pancreatitis, flatulence and nausea. It is also possible to have hemorrhagic diarrhea, which can occasionally be a sign of enterocolitis (also pseudomembranous colitis);
• problems with the hepatobiliary system: increased levels of liver enzymes (ALP with ALT and AST, as well as GGT) and blood bilirubin levels. In addition, jaundice, hepatitis and severe liver disease (including cases of acute liver failure) develop - mainly in people with severe forms of underlying pathologies;
• lesions of the subcutaneous layers and epidermis: itching, intolerance to UV and solar radiation, rashes, TEN, urticaria, hyperhidrosis, Stevens-Johnson syndrome, MEE and photosensitivity. Sometimes signs from the mucous membranes and epidermis appear after the first use;
• Disorders of connective tissue, muscle and bone: manifestations affecting tendons – including tendinitis, myalgia, arthritis and arthralgia, as well as rupture of ligaments, tendons or muscles. Muscle weakness may occur, which is especially important in people with rhabdomyolysis or severe myasthenia gravis;
• disorders of the urinary system and kidneys: increased plasma creatinine and ARF values (for example, due to tubulointerstitial nephritis);
• Systemic symptoms: a feeling of general weakness, pain reactions (in the limbs, back and sternum), asthenia, increased temperature and attacks of porphyria in people with this disease.

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Overdose

Signs of overdose: loss of consciousness, nausea, dizziness, seizures, erosions in the mucous membranes, prolongation of the QT interval or increased intensity of symptoms of other adverse reactions. In case of poisoning, the patient's condition must be closely monitored (including ECG readings).

Symptomatic measures are taken. Hemodialysis procedures (including CAPD or peritoneal dialysis) do not allow excretion of levofloxacin. Also, the drug has no antidotes.

Interactions with other drugs

Aluminum- or magnesium-containing antacids, as well as medications that contain zinc or iron salts, and also didanosine.

The absorption of the drug is significantly reduced when combined with the above-mentioned agents. The combined use of fluoroquinolones and multivitamins that contain zinc causes a decrease in the degree of absorption of the latter. It is necessary to observe intervals between the use of such medications (their duration is at least 120 minutes).

Calcium salts have only minimal effect on the absorption of levofloxacin.

Sucralfate.

The bioavailability of levofloxacin is significantly reduced when combined with sucralfate. The interval between the use of these drugs should be at least 2 hours.

Fenbufen with theophylline or similar NSAIDs.

An extremely strong decrease in seizure threshold limits may be observed in the case of a combination of quinolones with the above drugs and other elements that have a similar medicinal effect. The level of levofloxacin increases by about 13% when using fenbufen.

Cimetidine with probenecid.

It has been statistically proven that the above mentioned agents affect the excretion pattern of levofloxacin. The values of clearance of the substance inside the kidneys are reduced by 34% (with probenecid) and by 24% (with cimetidine). Such properties allow these drugs to block the excretion of Zolev through the tubules.

The pharmacokinetic parameters of levofloxacin remain unchanged when combined with digoxin, calcium carbonate, warfarin, as well as ranitidine and glibenclamide.

Cyclosporine.

The half-life of cyclosporine is increased by 33% when combined with the drug.

Drugs that have an antagonistic effect on vitamin K.

Combined use with such drugs (for example, warfarin) increases the level of coagulation parameters (INR or PT) or increases the severity of bleeding. Because of this, people taking such drugs together with levofloxacin need to monitor coagulation values.

Medicines that prolong the QT interval.

As with other fluoroquinolones, levofloxacin should be used with caution in individuals taking medications such as macrolides, tricyclics, antipsychotics, and category 1A and 3 antiarrhythmics.

Levofloxacin has no effect on the pharmacokinetic properties of theophylline, the metabolism of which occurs mainly with the participation of CYP 1A2, from which it can be concluded that levofloxacin does not inhibit CYP 1A2 activity.

The medicine does not interact with food, so it can be used without reference to its intake. It is prohibited to drink alcoholic beverages during treatment with levofloxacin.

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Storage conditions

Zolev must be stored in a dark and dry place, out of the reach of small children. The solution must not be frozen. Temperature values are a maximum of 30°C (tablets) or 25°C (solution).

Shelf life

Zolev can be used within 2 years from the date of release of the therapeutic drug.

Application for children

Prescribing the medication to persons under 18 years of age is prohibited because there is a risk of damage to cartilage in the joint area.

Analogues

The analogues of the drug are Tavanic, Levomak with Levolet and Flexid, as well as Leflocin, Lefloq, Levofloxacin and Levobact.