Клабакс ODES

General characteristics. Structure:

Active agent: кларитромицин - 500 mg
Excipients: a gipromeloza, lactoses monohydrate, cellulose microcrystallic, povidone, silicon dioxide colloid, the sodium stearylfumarating, talc, magnesium stearate.
Film covering: dye опадрай yellow 20H52875 (a gipromelloza, propylene glycol, vanillin, titanium dioxide, a hypro rod, talc, dye quinoline of yellow 18% - 24%).
Blackened black Opacode-S-1-17734 (shellac of 45% (20% etherified) in SD-45 alcohol, dye ferrous oxide black, N butanol, propylene glycol, methanol, isopropanol, ammonium hydroxide 28%).

Description. Oval, biconvex light yellow tablets, film coated, with a napechatka black CLNXL ink on one party.

Pharmacological properties:

Pharmacodynamics. The Makrolidny bacteriostatic antibiotic of the second generation from group of macroleads of a broad spectrum of activity. Breaks synthesis of protein of microorganisms (communicates with 50S in subunit of a membrane of ribosomes of a microbic cell). It is active in the relation: Streptococcus agalactiae (Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae), Haemophilus influenzae (parainfluenzae), Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamidia pneumoniae (trachomatis), Moraxella (Branhamella) catarrhalis, Bordetella pertussis, Propionibacterium acnes, Staphylococcus aureus, Ureaplasma urealyticum, Toxoplasma gondii, Corynebacterium spp., Borrelia burgdorferi, Treponema pallidum, Pasteurella multocida, some anaerobe bacterias (Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus) and all mycobacteria, except M.tuberculosis.
The main metabolite of a klaritromitsin in a human body is microbiological active metabolite 14-гидроксикларитромицин. Microbiological activity of a metabolite same as at initial substance, or is 1-2 times weaker concerning the majority of microorganisms. The exception makes H.influenzae concerning which efficiency of a metabolite is twice higher. Initial substance and its main metabolite render either the additive, or synergy effect concerning H.influenzae in the conditions of in vitro and in vivo depending on culture of bacteria.

Pharmacokinetics. Klaritromitsin is metabolized in system of P450 3A cytochrome (CYP3A) of a liver. Absolute bioavailability makes about 50%. At multiple dose of a dose of drug of cumulation it is not revealed, and the nature of metabolism in a human body did not change.
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 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.
Reception of a klaritromitsin of the prolonged action inside in a dose of 500 mg a day allows to support equilibrium levels of the maximum concentration of a klaritromitsin and 14-gidroksiklaritromitsin in a blood plasma. Equilibrium maximum concentration (Cmax) of a klaritromitsin and 14-gidroksiklaritromitsin in plasma make 1.3 mkg/ml and 0.48 mkg/ml respectively. Elimination half-lives of initial drug and its main metabolite make respectively 5.3 hours and 7.7 hours. At reception of a klaritromitsin of the prolonged action inside in a dose of 1000 mg a day (2 tablets on 500 mg) the equilibrium Cmax levels of a klaritromitsin and 14-gidroksiklaritromitsin average 2.4 mkg/ml and 0.67 mkg/ml respectively. Elimination half-lives of initial drug and its main metabolite make respectively 5.8 hours and 8.9 hours. Value of time of achievement of the maximum concentration (Tmax) at reception of doses on 500 mg and 1000 mg a day makes about 6 hours. At an equilibrium state the level of a 14-gidroksiklaritromitsin does not increase in proportion to doses of a klaritromitsin, and elimination half-lives of a klaritromitsin and its main metabolite increase with increase in a dose. Nonlinear character of pharmacokinetics of a klaritromitsin, is connected with reduction of education 14-hydroxylated and N-demetilirovannogo of metabolites at use of higher doses that indicates nonlinearity of metabolism of a klaritromitsin at reception of high doses.
With urine about 40% of a dose of a klaritromitsin, through intestines - about 30% are allocated.
Klaritromitsin and 14-gidroksiklaritromitsin are widely distributed in fabrics and liquids of an organism. After oral administration of a klaritromitsin its content in cerebrospinal fluid remains low (at normal permeability of a blood-brain barrier of 1-2% of level in blood serum). Content in fabrics usually several times is more than contents in blood serum.
Abnormal liver functions:
At patients with moderate and heavy disturbance of a functional condition of a liver, but with the kept function of kidneys of correction of a dose of a klaritromitsin it is not required. Equilibrium concentration in a blood plasma and system clearance of a klaritromitsin does not differ at patients of this group and healthy patients. Equilibrium level of concentration of a 14-gidroksiklaritromitsin at people with abnormal liver functions is lower, than at healthy.
Renal failure:
At a renal failure the minimum and maximum maintenance of a klaritromitsin in a blood plasma, an elimination half-life, the area under a curve concentration time of a klaritromitsin and 14-OH metabolites increases. The constant of elimination and removal with urine decrease. Extent of changes of these parameters depends on degree of a renal failure.
Patients of advanced age:
Patients of advanced age have a level of a klaritromitsin and than it 14-OH metabolites in blood was higher, and removal more slowly, than at group of young people. Consider that changes of pharmacokinetics at elderly patients are connected, first of all, with changes of clearance of creatinine and a functional condition of kidneys, but not patients with age.

Indications to use:

Клабакс® ODES it is shown for treatment of the infectious diseases caused by sensitive microorganisms. Treat these diseases:
• Infections of a lower part of respiratory tracts (bronchitis, pneumonia).
• Infections of an upper part of respiratory tracts (pharyngitises, sinusitis), otitises.
• Infections of skin and soft tissues (folliculites, erysipelatous inflammation).
• The extended or localized mikobakterialny infections caused by Mycobacterium avium and Mycobacterium intracellulare. The localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii.
• Клабакс® ODES it is shown for liquidation of H.pylori and decrease in frequency of a recurrence of an ulcer of the duodenum associated with H.pylori.

Route of administration and doses:

Adults and children are more senior than 12 years:
Usually Klabaks® of ODES of a tablet of the prolonged action appoint 500 mg during food once a day. In hard cases the dose is increased to 500 mg by 2 times a day.
The tablets Klabaks® ODES of the prolonged action cannot be broken, chewed, they need to be swallowed entirely.
Duration of treatment is 7-14 days.
For patients with KK of 30-60 ml/min. only at heavy infections appointment in a dose of 500 mg of 1 times a day is possible (i.e. decrease in a daily dose by 50%).

Features of use:

In the presence of chronic diseases of a liver it is necessary to carry out regular control of enzymes of blood serum.
With care appoint against the background of the drugs which are metabolized a liver (it is recommended to measure their concentration in blood).
In case of joint appointment with warfarin or other indirect anticoagulants it is necessary to control a prothrombin time.
It is necessary to pay attention to a possibility of cross stability between klaritromitsiny and other antibiotics from group of macroleads, and also lincomycin and clindamycin.
At prolonged or repeated use of drug development of superinfection is possible (repeated infection with the same activators against the background of the developed disease).
Children up to 12 years are recommended to apply Klabaks® in a dosage form of a granule to preparation of suspension for intake 250mg/5ml, 125 mg / 5мл.

Side effects:

Complaints from digestive tract (nausea, dyspepsia, abdominal pains, vomiting and diarrhea) are most often noted. There are messages on development of pseudomembranous colitis from medium-weight to life-threatening. Headaches, disturbances of taste and passing increase in activity of enzymes of a liver belong to other side reactions.
There are messages on exceptional cases of development of paresthesia, and also hepatitis with increase in level of enzymes of a liver in blood and development of a cholestasia and jaundice which in certain cases was heavy, but, as a rule, reversible. The liver failure with a lethal outcome was in exceptional cases observed.
Increase in concentration of creatinine in serum, development of intersticial nephrites, development of a renal failure is known of exceptional cases.
At reception of a klaritromitsin allergic reactions which intensity varied from a small tortoiseshell and skin rash to an anaphylaxis and Stephens-Johnson's syndrome were observed.
There are messages on a hearing loss during treatment klaritromitsiny which was in most cases recovered after drug withdrawal. Also there can be taste perception changes arising, as a rule, together with taste disturbance.
There are data on development of glossites, stomatitises, candidiasis of a mucous membrane of an oral cavity and language discoloration during treatment klaritromitsiny. It is reported also about discoloration of teeth reversible in most cases at the patients receiving кларитромицин.
The hypoglycemia was in rare instances noted; in a number of these cases the hypoglycemia developed at the patients accepting during treatment klaritromitsiny hypoglycemic means for oral administration or insulin.
It is reported about separate cases of thrombocytopenia and a leukopenia.
At reception of a klaritromitsin tranzitorny side effect on the central nervous system was observed: dizziness, alarm, fear, sleeplessness, nightmares, sonitus, confusion of consciousness, disorientation, hallucinations, psychoses and depersonalization.
At treatment klaritromitsiny, as well as when using other macroleads, lengthening an interval of QT, ventricular arrhythmia, including a ventricular Bouveret's disease and trembling or ventricular fibrillation was extremely seldom observed.
Overdose
 Development of symptoms from digestive tract (nausea, vomiting, diarrhea) is probable; headache, confusion of consciousness.
 At overdose the immediate gastric lavage and a symptomatic treatment is necessary. The hemodialysis and peritoneal dialysis do not lead to considerable change of level of a klaritromitsin in blood serum.

Interaction with other medicines:

At a concomitant use increases concentration in blood of the drugs which are metabolized in a liver by means of P450 cytochrome enzymes - indirect anticoagulants, carbamazepine, theophylline, an astemizol, tsizaprid, terfenadin (by 2-3 times), a triazolama, midazolam, cyclosporine, Disopyramidum, Phenytoinum, a rifabutin, a lovastatin, digoxin, ergot alkaloids, etc.
It is reported about exceptional cases of an acute necrosis of the skeletal muscles matching on time co-administration of a klaritromitsin and inhibitors of gidroksimetilglutaril-KOA-reduktazy - a lovastatina and a simvastatina.
There are messages about increases in concentration of digoxin in plasma of the patients receiving at the same time digoxin and tablets of a klaritromitsin. At such patients it is necessary to control constantly the content of digoxin in serum to avoid digitalis intoxication.
 Klaritromitsin can reduce clearance of a triazolam and, thus, increase its pharmacological effects with development of drowsiness and confusion of consciousness.
 Simultaneous use of a klaritromitsin and ergotamine (ergot derivatives) can lead to the acute ergotaminovy intoxication which is shown a heavy peripheral vasospasm.
Co-administration by the HIV-positive adult of a zidovudine orally and tablets of a klaritromitsin can lead to reduction of equilibrium concentration of a zidovudine. Considering what кларитромицин probably changes absorption  of the zidovudine appointed inside along with it, this interaction substantially manages to be avoided at reception of a klaritromitsin and zidovudine in various hours of days (with an interval not less than 4 hours).
At co-administration of a klaritromitsin and ritonavir values of serumal concentration of a klaritromitsin increase. Dose adjustment of a klaritromitsin in these cases with normal function of kidneys is not required from patients. However at patients with clearance of creatinine from 30 to 60 ml/min. the dose of a klaritromitsin should be lowered by 50%, and at clearance of creatinine  less than 30 ml/min. it is not necessary to appoint tablets of a klaritromitsin of the prolonged action. Such patient it is appointed кларитромицин bystry release of 250 mg or 500 mg. At simultaneous treatment ritonaviry it is not necessary to appoint кларитромицин in doses over 1 g/days.

Contraindications:

• Клабакс® ODES it is contraindicated to patients with hypersensitivity to antibiotics from group of macroleads.
• At treatment klaritromitsiny not to appoint ergot derivatives.
• At treatment klaritromitsiny it is forbidden to accept цизаприд, Pimozidum, астемизол and терфенадин (see also section Interaction with other medicines).
At the patients accepting these drugs along with klaritromitsiny increase in their concentration in blood is noted. At the same time lengthening of an interval of QT and development of cardiac arrhythmias, including a ventricular Bouveret's disease, fibrillation of ventricles and trembling or ventricular fibrillation is possible.
• Heavy abnormal liver functions and/or kidneys (clearance of creatinine (CC) less than 30 ml/min.).
• Porphyria.
• Children's age up to 12 years (only for this dosage form).
Use at pregnancy and a lactation
 Safety of a klaritromitsin during pregnancy and feeding by a breast is not established. Therefore during pregnancy кларитромицин appoint only in case of lack of alternative therapy if the estimated advantage exceeds possible risk for a fruit.
Klaritromitsin gets into women's milk therefore in need of its use in the period of a lactation feeding by a breast should be stopped.

Overdose:

Development of symptoms from digestive tract (nausea, vomiting, diarrhea) is probable; headache, confusion of consciousness.
 At overdose the immediate gastric lavage and a symptomatic treatment is necessary. The hemodialysis and peritoneal dialysis do not lead to considerable change of level of a klaritromitsin in blood serum.

Storage conditions:

List B. To store at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated, 500 mg
 On 5 tablets in the blister from PVC/PVdH; 1 or 2 blisters together with the application instruction in a cardboard pack
 On 7 tablets in the blister from PVC/PVdH; 1 or 2 blisters together with the application instruction in a cardboard pack.