Klabel

General characteristics. Structure:

Active ingredient: 250 mg or 500 mg of a klaritromitsin.

Excipients: sodium of a kroskarmelloz, starch prezhelatinizirovanny, silicon dioxide colloid anhydrous (Aerosil 200), povidone, stearic acid, magnesium stearate, talc, cellulose microcrystallic.

Structure of a cover: HPMC 2910/gipromelloza 15 of Wednesday, HPMC 2910/of a gipromelloz 6 Wednesday, titanium E 171 dioxide, propylene glycol, hydroxypropyl cellulose, polysorbate 80, quinolinic yellow 18 - 24% (Е 104), sorbic acid FCC, vanillin.

Antibiotic of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics / Klaritromitsin is a semi-synthetic antibiotic of group of macroleads. The mechanism of action consists in suppression of synthesis of protein in a bacterial cell. Klaritromitsin is highly active concerning a wide range of aerobic, anaerobic, gram-positive and gram-negative bacteria.

The main metabolite of a klaritromitsin is the active metabolite – 14-gidroksiklaritromitsin which also has antibacterial activity. In particular, concerning Haemophilus influenzae efficiency of a metabolite is twice higher than efficiency of a klaritromitsin. At the same time 14-gidroksiklaritromitsin in comparison with klaritromitsiny by from 4 to 7 times is less active concerning strains of Mycobacterium avium complex in comparison with klaritromitsiny.

Клабел® it is active concerning the following microorganisms:

Aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis.

Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae.

Mycobacteria: Mycobacterium avium complex supporting Mycobacterium avium, Mycobacterium intracellulare.

Helicobacter: Helicobacter pylori.

Pharmacokinetics. After intake кларитромицин it is quickly soaked up from digestive tract. Absolute bioavailability in a klaritromitsin makes approximately from 50% to 55%. Klaritromitsin contacts proteins of a blood plasma for 70% in concentration from 0.45 to 4.5 mkg/ml. At concentration of 45 mkg/ml extent of binding decreases to 41%, it is probable as a result of saturation of places of binding. It is observed only at the concentration which are repeatedly exceeding therapeutic. The concomitant use with food leads to insignificant delay of absorption of a klaritromitsin and increase time of achievement of peak concentration from 2 to 2.5 o'clock. At administration of drug in a dose of 500 mg each 8 - 12 h – time the elimination half-life makes to 5 - 7 h Klaritromitsin forms the concentration several times exceeding concentration in a blood plasma in fabrics.

Klaritromitsin is brought with urine in an invariable type of 15 - 20%, in the form of the main metabolite of a 14-gidroksiklaritromitsin – 10 – 15%.

Indications to use:

- infections of a lower part of respiratory tracts (bronchitis, pneumonia, etc.);

- infections of an upper part of respiratory tracts (sinusitis, pharyngitis, etc.);

- infections of skin and soft tissues (folliculites, cellulitises, эризипелоид, etc.);

- the disseminated or localized mikobakterialny infections caused by Mycobacterium avium or Mycobacterium intracellulare, the localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasii;

- for prevention of the disseminated infections caused by the Mycobacterium avium (IAC) complex in HIV-positive patients with quantity of CD4 lymphocytes ≤ 100/mm3;

- for an eradikation of H. pylori at patients with a duodenum ulcer at oppression of secretion of hydrochloric acid which is rendered омепразол or ланзопразол (activity of a klaritromitsin against H. pylori at a neutral rn above, than at an acid rn);

- at treatment of dontogenous infections.

Route of administration and doses:

At infections of a lower part of respiratory tracts, an upper part of respiratory tracts, infections of skin and soft tissues the recommended drug KLABEL® dose for adults makes 250 mg twice a day, at heavier infections the dose is increased to 500 mg twice a day. The usual duration of treatment makes 5-14 days (for community-acquired pneumonia and sinusitis the course makes 6 – 14 days).

КЛАБЕЛ® it is possible to apply irrespective of meal.

Prevention and treatment of patients with a mikobakterialny infection: the recommended dose for adults makes 500 mg twice a day.

Duration of treatment of not tuberculosis mikobakterialny tuberculosis infections is defined by the doctor in an individual order.

Duration of treatment of IAC of infections at patients with AIDS depends on clinical and microbiological performance of drug. In such cases КЛАБЕЛ® it is necessary to apply in a complex with other antimikobakterialny means.

For an eradikation of H. pylori at patients with a duodenum ulcer (adults). Triple therapy. ÈïÇüàï® 500 twice a day, лансопразол 30 mg twice a day and amoxicillin of 1000 mg twice a day within 10 days.

ÈïÇüàï® 500 twice a day, amoxicillin of 1000 mg twice a day and омепразол 20 mg a day within 7 - 10 days.

Double therapy. ÈïÇüàï® 500 rub once a day, омепразол 40 mg once a day, then омепразол 20 mg or 40 mg within 14 days once a day.

ÈïÇüàï® 500 rub once a day, лансопразол 60 mg within 14 days once a day. Further decrease in acidity leads to scarring of an ulcer.

Treatment of dontogenous infections: on 250 mg twice a day within 5 days.

Features of use:

Cases of pseudomembranous colitis are reported at use of almost all antibacterial agents, and on weight can be from easy to life-threatening degree. Therefore, it is important to take into account this diagnosis at patients who have a diarrhea which followed after reception of antibacterial agent.

About development of diarrhea, from easy severity to the colitis with a fatal outcome caused by Clostridium difficile (CDAD) it was reported at use practically of all antibacterial drugs, including a klaritromitsin. Strengthening of symptoms of myasthenia gravis at the patients receiving КЛАБЕЛ® is possible.

It was reported about development of kolkhitsinovy toxicity (including with a fatal outcome) at combined use of a klaritromitsin and colchicine, especially at elderly patients, including against the background of a renal failure.

Because of risk of lengthening of an interval of QT it is necessary to apply with care КЛАБЕЛ® at patients with the state of health connected with the raised tendency to development of lengthening of an interval of QT and torsades de pointes.

As existence of resistance of Streptococcus pneumoniae to macroleads is possible, it is important to carry out the sensitivity test at appointment КЛАБЕЛ® for treatment of not hospital pneumonia. In case of hospital pneumonia кларитромицин it is necessary to apply in a combination with other corresponding antibiotics.

With care appoint drug to patients with abnormal liver functions. In the presence of chronic diseases of a liver it is necessary to carry out regular control of enzymes of blood serum. At patients with a liver failure and normal function of kidneys кларитромицин it is possible to apply without dose adjustment. However in the presence at the patient of a renal failure of heavy degree (clearance of creatinine <30 ml/min.) regardless of the accompanying liver failure, it is necessary to reduce a dose twice (250 mg once a day or 250 mg twice a day at heavier infections) or to increase intervals between administrations of drug. Duration of treatment should not exceed 14 days.

Peroral hypoglycemic means / Insulin. The combined use КЛАБЕЛ® and peroral hypoglycemic means and/or insulin can cause the expressed hypoglycemia. At simultaneous use with hypoglycemic means, such as натеглинид, пиоглитазон, репаглинид and розиглитазон кларитромицин can inhibit CYP3A enzyme that can cause a hypoglycemia. Careful monitoring of level of glucose is recommended.

Peroral anticoagulants. At combined use of a klaritromitsin with warfarin there is a risk of developing of serious bleeding, substantial increase of an indicator INR (the international normalized relation) and a prothrombin time. Until patients accept at the same time кларитромицин and peroral anticoagulants, it is necessary to control often an indicator of MNO and a prothrombin time.

GMG-KOA-reduktazy inhibitors. The combined use of a klaritromitsin with lovastatiny or simvastatiny is contraindicated (see. "Contraindications").

As well as other macroleads, кларитромицин led to increase in concentration of inhibitors of GMG-KOA-reduktazy. It was seldom reported about development of a rabdomioliz in patients at combined use of these medicines. Observation of patients regarding existence of signs and symptoms of a myopathy is necessary.

It was seldom reported about development of a rabdomioliz in patients at combined use of a klaritromitsin with atorvastatiny or rozuvastatiny. In case of simultaneous use the dose of an atorvastatin or a rozuvastatin needs to be lowered as much as possible. The relevant decision concerning correction of a dose of statine or use of statine which does not depend on metabolism of CYP3A has to be made (for example, флувастатин or правастатин).

Features of influence of medicine on ability to manage the vehicle or potentially dangerous mechanisms.

Considering side effects of drug it is necessary to be careful when driving and potentially dangerous mechanisms.

Side effects:

The most frequent and general side reactions at treatment klaritromitsiny are the abdominal pain, diarrhea, nausea, vomiting and distortion of taste. These side reactions which are usually softly expressed are also coordinated with the known profile of safety of makrolidny antibiotics.

- diarrhea, vomiting, abdominal pain, lock and nausea, change of flavoring feelings, disorders of sense of smell and taste;

- urticaria, moderately severe skin rash to an acute anaphylaxis and Stephens-Johnson's syndrome, a toxic epidermal necrolysis, medicamentous skin reaction which is followed by an eosinophilia and system manifestations (DRESS), an acne, Shenleyna-Genokh's disease;

- language inflammation, stomatitis and barmy mycosis of an oral cavity, anorexia, pancreatitis, discoloration of language and teeth;

- thrombocytopenia, leukopenia, neutropenia, eosinophilia, agranulocytosis;

- dizziness, headache, uneasiness, nervousness;

- concern, sleeplessness, nightmares, opacification of consciousness, hallucination and perhaps psychosis;

- hepatocellular and/or cholestatic hepatic dysfunction with or without jaundice and increase in liver enzymes, a liver failure;

- hypoglycemia;

- a hearing loss, a ring in ears;

- ventricular premature ventricular contraction, expansion of an interval of QT, ventricular tachycardia, including polymorphic ventricular tachycardia like "pirouette";

- infection, vaginal infections;

- asthma, nasal bleeding, vascular embolism of lungs;

- an esophagitis, a gastroesophageal reflux disease, gastritis, a proctalgia, stomatitis, a glossitis, abdominal distention, dryness in a mouth, an eructation, a meteorism;

- muscular spasms, skeletal and muscular rigidity, mialgiya;

- increase in creatinine and urea of blood;

- indisposition, fever, adynamy, stethalgia, fever, increased fatigue;

- change of a ratio albumine-globulin, increase in level of an alkaline phosphatase and lactate dehydrogenase in blood serum;

- pseudomembranous colitis, erysipelatous inflammation, erythrasma;

- рабдомиолиз (in some messages on emergence of a rabdomioliz when кларитромицин applied at the same time with statines, fibrata, colchicine or Allopyrinolum), a myopathy;

 - renal failure, intersticial nephrite;

- increase in a prothrombin time, urine discoloration.

Patients with disturbance of immune system. At patients with AIDS and other patients with disturbance of immune system applying high doses of a klaritromitsin a long time than it is recommended for treatment of mikobakterialny infections, it is not always possible to distinguish the side reactions connected using drug and symptoms of the basic or associated diseases.

Interaction with other medicines:

Combined use of Klabel® with:

- cyclosporine, Disopyramidum, alprazolamy, carbamazepine, Disopyramidum, to triazoles ergot alkaloids, Methylprednisolonum, midazolam, omeprazoly, Pimozidum, quinidine, rifabutiny, sildenafily, takrolimusy, vinblastine, lovastatiny and simvastatiny;

leads to increase in their concentration in a blood plasma. The similar mechanism of interaction is noted also at use of medicines, such as Phenytoinum, theophylline and Valproatum;

- digoxin, leads to increase in content of digoxin in a blood plasma. At such combination it is necessary to control the content of digoxin in serum in order to avoid digitalis intoxication;

- a zidovudine, at concomitant oral administration at VICh-infi-tsirovannykh adult patients, leads to decrease in equilibrium level of concentration of a zidovudine. As кларитромицин influences absorption of a zidovudine, reception of these two drugs should be divided in time with an interval not less than 4 h;

- ritonaviry, significantly slows down metabolism of a klaritromitsin and values of serumal concentration of a klaritromitsin increase. Essential delay of process of formation of a 14-gidroksiklaritromitsin is observed. In this case patients without renal failure have no need to adjust a dose of a klaritromitsin. At KK of 60-30 ml/min. the dose of a klaritromitsin has to be reduced to the maximum dose of 500 mg of 1 times/days. At reception of a ritonavir it is not necessary to appoint at the same time a dose of a klaritromitsin more than 1 g/days;

- other drugs of group of macroleads, such as lincomycin and clindamycin, development of cross resistance is possible;

- flukonazoly, leads to increase in average constant minimum concentration (Cmin) in a klaritromitsin and level in a blood plasma (AUC); constant concentration 14-OH klaritromitsin significantly does not change;

- warfarin and other peroral anticoagulants, кларитромицин can exponentiate their action. At simultaneous use of a klaritromitsin and peroral anticoagulants it is necessary to control a prothrombin time;

- hypoglycemic drugs, observe a hypoglycemia;

- triazolamy, reduces clearance of a triazolam that can lead to increase in pharmacological effect with development of drowsiness and confusion of consciousness.

Influence of a klaritromitsin on pharmacokinetics of other medicines. Antiarrhytmic means. There are messages on development of the piruetny ventricular tachycardia which arose at simultaneous use of a klaritromitsin with quinidine or Disopyramidum. It is recommended to carry out ECG monitoring for early detection of lengthening of an interval of QT. During therapy by Klabel it is necessary to watch concentration of these drugs in blood serum.

Combined use of a klaritromitsin, the known inhibitor of CYP3A enzyme, and the drug which is generally metabolized CYP3A can lead to increase in concentration of the last in a blood plasma that, in turn, can strengthen or prolong its therapeutic effect and risk of emergence of side reactions.

It is necessary to be careful at use of a klaritromitsin for the patients receiving therapy by medicines – CYP3A substrates, especially if CYP3A substrate has narrow therapeutic range (for example, carbamazepine) and/or is extensively metabolized by this enzyme.

Change of a dose, and, whenever possible, careful monitoring of serumal concentration of the medicine which is metabolized CYP3A at patients who at the same time apply кларитромицин can be necessary.

It is known (or it is supposed) that the following medicines or groups of drugs are metabolized by the same CYP3A an isoenzyme: to alprazola, астемизол, carbamazepine, цилостазол, цизаприд, cyclosporine, Disopyramidum, alkaloids of horns, ловастатин, Methylprednisolonum, midazolam, омепразол, peroral anticoagulants (for example, warfarin), Pimozidum, quinidine, рифабутин, sildenafit, симвастатин, такролимус, терфенадин, to triazoles and vinblastine. The similar mechanism of interaction is noted at use of Phenytoinum, theophylline and Valproatum which are metabolized by other isoenzyme of system of P450 cytochrome.

Other types of interactions. Colchicine: at simultaneous use of a klaritromitsin and colchicine colchicine exposure can increase. It is necessary to watch a condition of patients for identification of clinical symptoms of toxicity of colchicine. Digoxin: increase in concentration of digoxin in blood serum of the patients receiving кларитромицин together with digoxin is possible. At some patients signs of digitalis toxicity, including potentially fatal arrhythmias developed. It is necessary to control carefully concentration of digoxin in blood serum of patients at its use with klaritromitsiny.

Zidovudine: decrease in equilibrium concentration of a zidovudine in blood serum is possible.

Verapamil: it was reported about development of arterial hypotension, a bradyarrhythmia and lactoacidosis at combined use of a klaritromitsin and verapamil.

Klaritromitsin does not interact with oral contraceptives.

Contraindications:

- hypersensitivity to makrolidny antibiotics or other components of drug;

- simultaneous use of a klaritromitsin and any of the following drugs: астемизол, цизаприд, Pimozidum, терфенадин (can lead to lengthening of an interval of QT and development of cardiac arrhythmias, including ventricular tachycardia, fibrillation of ventricles and piruetny ventricular tachycardia (torsade de pointes), ergotamine or dihydroergotamine (can lead to an ergotoksichnost), ловастатин, симвастатин (because of risk of emergence of a rabdomioliz);

- the patients who had lengthening of an interval of QT or ventricular cardiac arrhythmias in the anamnesis including piruetny ventricular tachycardia (torsade de pointes);

- simultaneous use of colchicine and the R-glycoprotein or strong CYP3A4 inhibitor to patients with a renal or liver failure;

- the expressed renal failure (at clearance of creatinine less than 30 ml/min.);

- hypersensitivity to antibiotics of group of macroleads;

- porphyria;

- pregnancy and period of a lactation;

- heavy abnormal liver functions;

- children's and teenage age up to 18 years.

Overdose:

Symptoms: nausea, vomiting, abdominal pains, diarrhea, change of a mental state, paranoid behavior, hypopotassemia and anoxemia.

Treatment: immediate gastric lavage and symptomatic therapy. The hemodialysis and peritoneal dialysis is ineffective.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children! Period of storage 3 years. Not to apply after a period of validity.  

Issue conditions:

According to the recipe

Packaging:

For a dosage of 250 mg: On 5 or 7 tablets, film coated in a blister strip packaging from a film of polyvinyl chloride and printing aluminum foil.

On 1 (on 7 tablets) or 2 (on 5 or 7 tablets) planimetric packagings together with the instruction on a medical use in the state and Russian languages place in a pack from a cardboard with the hologram of firm - producer.

For a dosage of 500 mg: on 7 tablets place in a blister strip packaging from a film of polyvinyl chloride and printing aluminum foil.

On 2 planimetric packagings together with the instruction on a medical use in the state and Russian languages place in a pack from a cardboard with the hologram of firm – producer.