Klaritrosin

General characteristics. Structure:

Tablets, film coated yellow color, round, biconvex form; on cross section - one layer of white or almost white color.

Active ingredient: кларитромицин  250 mg

Excipients: povidone (polyvinylpirrolidone) - 21 mg, sodium carboxymethylstarch - 40 mg, lactoses monohydrate - 20 mg, potato starch - 60.5 mg, silicon dioxide colloid (aerosil) - 5 mg, magnesium stearate - 5 mg, talc - 15 mg, cellulose microcrystallic - to 500 mg.

Structure of a cover: a gipromelloza - 10.53 mg, titanium dioxide - 3.85 mg, a macrogoal of 4000 - 10.52 mg, dye tropeolin O - 0.1 mg.

Tablets, film coated yellow color, round, biconvex form; on cross section - one layer of white or almost white color.

Active ingredient: кларитромицин 500 mg

Excipients: sodium carboxymethylstarch - 80 mg, povidone (polyvinylpirrolidone) - 42 mg, lactoses monohydrate - 40 mg, potato starch - 121 mg, silicon dioxide colloid (aerosil) - 10 mg, magnesium stearate - 10 mg, talc - 30 mg, cellulose microcrystallic - to 1 g.

Structure of a cover: a gipromelloza - 21.06 mg, titanium dioxide - 7.7 mg, a macrogoal of 4000 - 21.04 mg, dye tropeolin O - 0.2 mg.

Pharmacological properties:

Klaritromitsin is a semi-synthetic antibiotic of a broad spectrum of activity from group of macroleads. Has antibacterial effect, interacting with 50S a ribosome subunit of sensitive bacteria and suppressing protein synthesis.

Tablets of the prolonged action represent a homogeneous crystal basis when which passing up to a GIT long release of active ingredient is provided.

Klaritromitsin showed high activity of in vitro against the standard and isolated cultures of bacteria. It is highly effective concerning many aerobic and anaerobic gram-positive and gram-negative microorganisms. Klaritromitsin is highly effective in vitro concerning Legionella pneumophila and Mycoplasma pneumoniae.

Enterobacteriaceae and Pseudomonas, also as well as other gram-negative bacteria which are not decomposing lactose, are steady against a klaritromitsin.

It is shown what кларитромицин has antibacterial effect against the following activators: gram-positive aerobic microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Listeria monocytogenes; gram-negative aerobic microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila, Pasteurella multocida, Helicobacter pylori, Campylobacter jejuni; intracellular microorganisms: Mycoplasma pneumoniae, Chlamydophila (Chlamydia) pneumoniae (TWAR), Chlamydia trachomatis, Borrelia burgorferi; anerob: Clostridium perfringes, Peptococcus niger, Propionibacterium acnes, Bacteroides melaninogenicus; mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC) - Mycobacterium avium, Mycobacterium intracellulare.

Products β-лактамаз do not exert impact on activity of a klaritromitsin. The majority of strains of stafilokokk, resistant to Methicillinum and Oxacillinum, have resistance and to a klaritromitsin.

Klaritromitsin has effect of in vitro and concerning the majority of strains of the following microorganisms (however safety and efficiency of use of a klaritromntsin in clinical practice is not confirmed with clinical trials and practical value remains not clear): gram-positive aerobic microorganisms (Streptococcus agalactiae, Streptococci (group C, F, G, Viridans); gram-negative aerobic microorganisms - Bordetella pertussis, Pasteurella multocida; gram-positive anaerobic microorganisms - Clostridium perfringes, Peptococcus niger, Propionibacterium acnes; gram-negative anaerobic microorganisms - Bacteroides melaninogenicus; spirochetes - Borrelia burgdorferi, Treponema pallidum; and also Campylobacter jejuni.

The main metabolite of a klaritromitsin in a human body is microbiological active metabolite 14-gidroksiklaritromitsin. Microbiological activity of a metabolite same as at initial substance, or is 1-2 times weaker concerning the majority of microorganisms. The exception makes Haemophilus influenzae concerning which efficiency of a metabolite is twice higher. Initial substance and its main metabolite render either the additive, or synergy effect concerning Haemophilus influenzae in the conditions of in vitro and in vivo depending on culture of bacteria.

 

Pharmacokinetics. Absorption

At intake кларитромицин it is well and quickly absorbed from a GIT. Bioavailability makes 50-55%. Food slows down absorption, significantly without influencing bioavailability. Cmax is reached less than in 3 h. After a single dose two peaks of Cmax are registered. The second peak is caused by ability of drug to concentrate in a gall bladder with the subsequent gradual or bystry release.

Distribution

Linkng with proteins of plasma - no more than 65-75%. At regular reception on 250 mg / Css of a klaritromitsin and its main metabolite - 1 mkg/ml and 0.6 mkg/ml respectively; T1/2 is 3-4 h and 5-6 h respectively. At increase in a dose up to 500 mg / Css of a klaritromitsin and its metabolite in plasma - 2.7-2.9 mkg/ml and 0.83-0.88 mkg/ml respectively; T1/2 is 4.8-5 h and 6.9-8.7 h respectively. In therapeutic concentration collects in lungs, skin and soft tissues (in them concentration by 10 times exceeds level in blood serum).

Metabolism

After intake of 20% of the accepted dose quickly it is hydrolyzed in a liver by isoenzymes of CYP3A4, CYP3A5, CYP3A7 of P450 cytochrome with formation of the main active metabolite - a 14-gidroksiklaritromitsina.

Removal

It is removed by kidneys and intestines (20-30% - in not changed look, other part - in the form of metabolites). At a single dose of 250 mg and 1.2 g kidneys remove 37.9% and 46%, by intestines - 40.2% and 29.1% respectively.

Pharmacokinetics in special clinical cases

At patients with a moderate and heavy abnormal liver function, but with the kept function of kidneys of correction of a dose of a klaritromitsin it is not required, Css and system clearance of a klaritromitsin do not differ from these indicators at healthy patients. Css of a 14-gidroksiklaritromitsin at people with abnormal liver functions is lower, than at healthy.

At patients with renal failures Cmax and Cmin in a blood plasma, T1/2, AUC of a klaritromitsin and a 14-gidroksiklaritromitsin increases. The constant of elimination and removal by kidneys decrease. Extent of changes of these parameters depends on degree of a renal failure.

Patients of advanced age have a level of a klaritromitsin and 14-gidroksiklaritromitsin in blood is higher, and removal more slowly, than at young people. 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.

The patients with HIV infection receiving кларитромицин in usual doses (500 mg 2), had similar Css of a klaritromitsin and a 14-gidroksiklaritromitsin to those at healthy people. However at use of a klaritromitsin in higher doses which can be required for treatment of mikobakterialny infections concentration of an antibiotic can exceed usual considerably. At the patients with HIV infection accepting кларитромицин in a dose of 1 g 2 g / in 2 receptions, Cssmax usually made 2-4 mkg/ml and 5-10 mkg/ml respectively. At use of drug in higher doses lengthening of T1/2 in comparison with that at the healthy people receiving кларитромицин in usual doses was noted. Increase in concentration in plasma and duration of T1/2 at purpose of a klaritromitsin in higher doses will be coordinated with the known nonlinearity of pharmacokinetics of drug.

At purpose of a klaritromitsin on 500 mg 3 in a combination with omeprazoly in a dose of 40 mg / there is an increase in T1/2 and AUC0-24 of an omeprazol. At all patients receiving a combination therapy in comparison with receiving one омепразол, increase in AUC0-24 of an omeprazol by 89% and T1/2 of an omeprazol by 34% was observed. At a klaritromitsin of Cmax, Cmin and AUC increased respectively by 10%, 27% and 15% in comparison with data when it was applied only кларитромицин without omeprazol. In an equilibrium condition of concentration of a klaritromitsin in a mucous membrane of a stomach in 6 h after inclusion in the group receiving a combination of drugs by 25 times surpassed those, in comparison with receiving one кларитромицин. Concentration of a klaritromitsin in stomach tissues in 6 h after reception of two drugs exceeded the data obtained in group of the patients receiving one кларитромицин twice.

Indications to use:

Treatment of the infectious and inflammatory diseases caused by activators, sensitive to a klaritromitsin:

— infections of lower parts of respiratory tracts (bronchitis, community-acquired pneumonia);

— infections of upper parts of respiratory tracts (pharyngitises, tonsillitis, sinusitis);

— infections of skin and soft tissues (folliculites, erysipelatous inflammation);

— dontogenous infections;

— for an eradikation of Helicobacter pylori and decrease in frequency of a recurrence of an ulcer of a duodenum;

— the widespread mikobakterialny infections caused by Mycobacterium avium and Mycobacterium intracellulare;

— prevention of spread of the infection caused by Mycobacterium avium complex (MAC).

Route of administration and doses:

Drug is accepted inside irrespective of meal.

To adults and children 12 years are more senior and/or with body weight more than 33 kg are appointed on 250 mg by each 12 h. The course of treatment makes 7-14 days.

At pharyngitis and tonsillitis, caused by Streptococcus pyogenes - on 250 mg each 12 h within 10 days.

At acute antritis - on 500 mg each 12 h within 14 days.

At an exacerbation of the chronic bronchitis caused by Haemophilus influenzae - on 500 mg each 12 h within 7-14 days; the caused Haemophilus parainfluenzae - on 500 mg each 12 h within 7 days; the caused Moraxella catarrhalis, Streptococcus pneumoniae - on 250 mg each 12 h within 7-14 days.

At the community-acquired pneumonia caused by Haemophilus influenzae - on 250 mg each 12 h within 7 days; the caused Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila (Chlamydia) pneumoniae - on 250 mg each 12 h within 7-14 days.

At the uncomplicated infections of skin and hypodermic cellulose caused by Staphylococcus aureus, Streptococcus pyogenes - on 250 mg each 12 h within 7-14 days.

For prevention and treatment of the infections caused by MAC, the recommended dose of a klaritromitsin - on 500 mg 2 Duration of treatment make 6 months and more. The maximum daily dose - 1 g.

At dontogenous infections the dose of a klaritromitsin makes 250 mg 2 within 5 days.

For Helicobacter pylori eradikation

The combined treatment by three drugs

— кларитромицин on 500 mg 2 + лансопразол on 30 mg 2sut + amoxicillin on 1000 mg 2 within 10 days;

— кларитромицин on 500 mg 2 + омепразол on 20 mg / 2sut + amoxicillin on 1000 mg 2 within 10 days.

The combined treatment by two drugs

— кларитромицин on 500 mg 3 + омепразол 40 mg/days within 14 days with appointment during the next 14 days of an omeprazol in a dose of 20 mg/days.

To children from 3 to 12 years кларитромицин appoint in the daily dose 15 mg/kg divided into 2 receptions within 10 days. The maximum daily dose - 1 g (1000 mg).

Patients with a chronic renal failure at clearance of creatinine have less than 30 ml/min. or with the content of serumal creatinine more than 290 µmol/l (3.3 mg / 100 the ml) a dose should be reduced twice or to double an interval between receptions. The maximum duration of treatment at patients of this group - 14 days.

Features of use:

At chronic diseases of a liver it is necessary to carry out regular control of activity of enzymes in blood serum.

With care appoint Klaritrosin® along with drugs, the metabolized liver enzymes (it is recommended to control concentration of drugs in blood).

In case of joint appointment with warfarin or other indirect anticoagulants it is necessary to control a prothrombin time.

At development of consecutive infection adequate therapy has to be appointed.

At emergence in time or after treatment of heavy and long diarrhea it is necessary to exclude the diagnosis of pseudomembranous colitis which demands immediate drug withdrawal and purpose of the corresponding treatment.

Influence on ability to driving of motor transport and to control of mechanisms

It is necessary to be careful at control of vehicles, mechanisms and when working, the psychomotor reactions demanding speed.

Side effects:

From the alimentary system: dyspepsia, nausea, vomiting, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of a mucous membrane of an oral cavity, discoloration of language and teeth, acute pancreatitis, increase in activity of hepatic transaminases, hepatocellular and cholestatic hepatitis, cholestatic jaundice; pseudomembranous colitis; a liver failure with a lethal outcome, generally against the background of serious associated diseases and/or the accompanying medicinal therapy.

From a nervous system: headache, dizziness, concern, sleeplessness, confusion of consciousness, disorientation, hallucinations, depersonalization, sensation of fear, psychosis, "dreadful" dreams, depression, spasms.

From an urinary system: intersticial nephrite, giperkreatininemiya.

From sense bodys: noise, a ring in ears, taste change, the hearing loss passing after drug withdrawal, disturbance of sense of smell.

From system of a hemopoiesis: thrombocytopenia (unusual bleedings, hemorrhages), leukopenia.

From cardiovascular system: ventricular tachycardia, including the pirouette type, trembling and ventricular fibrillation, lengthening of an interval of QT on an ECG.

Allergic reactions: skin rash, itch, small tortoiseshell, anaphylactic reactions, dermahemia, Stephens-Johnson's syndrome, toxic epidermal necrolysis.

From endocrine system: a hypoglycemia (including at a concomitant use of hypoglycemic means).

Others: mialgiya, consecutive infections (development of stability of microorganisms).

Interaction with other medicines:

At joint reception of a klaritromitsin and medicines, initially метаболизирущихся CYP3A isoenzyme, perhaps mutual increase in their concentration that can strengthen or prolong both therapeutic, and side effects. Joint reception with astemizoly, tsizapridy, Pimozidum, terfenadiny, ergotamine and other alkaloids of an ergot, alprazolamy, midazolam, triazolamy is contraindicated.

With care appoint with carbamazepine, tsilostazoly, cyclosporine, Disopyramidum, lovastatiny, Methylprednisolonum, omeprazoly, indirect anticoagulants (including warfarin), quinidine, rifabutiny, sildenafily, simvastatiny, takrolimusy, vinblastine, Phenytoinum, theophylline and valproic acid (are metabolized through other isoenzymes of P450 cytochrome). Dose adjustment of drug and control of concentration in blood is necessary.

At joint reception with tsizapridy, Pimozidum, terfenadiny and astemizoly increase in concentration of the last in blood, lengthening of an interval of QT, emergence of arrhythmia, including ventricular tachycardia, including the pirouette type and fibrillation of ventricles is possible.

At joint reception with ergotamine and dihydroergotamine perhaps acute poisoning with drugs of group of ergotamine (a vascular spasm, ischemia of extremities and other fabrics, TsNS).

Efavirenz, not Virapinum, rifampicin, рифабутин and rifapentine (P450 cytochrome inductors) reduce concentration of a klaritromitsin in plasma and weaken its therapeutic effect, and, at the same time, increase concentration of a 14-gidroksiklaritromitsin.

At joint reception of a flukonazol in a dose of 200 mg/days and a klaritromitsina in a dose of 1 g/days increase in Css and AUC of a klaritromitsin by 33% and 18% respectively is possible. Dose adjustment of a klaritromitsin is not required.

At joint reception of a ritonavir of 600 mg/days and a klaritromitsina of 1 g/days decrease in metabolism of a klaritromitsin (increase in Cmax by 31%, Css by 182% and AUC by 77%), full suppression of formation of a 14-gidroksiklaritromitsin is possible. At patients with a chronic renal failure dose adjustment is necessary: at KK of 30-60 ml/min. the dose of a klaritromitsin has to be reduced by 50%, at KK less than 30 ml/min. for 75%. Ritonavir it is not necessary to accept together with klaritromitsiny in the dose exceeding 1 g/days.

At joint reception with hnnidiny and Disopyramidum developing of ventricular tachycardia like "pirouette" is possible. Control of an ECG (increase in an interval of QT), serumal concentration of these medicines is necessary.

Klaritromitsin increases concentration of inhibitors of GMG-KOA-reduktazy (ловастатин, симвастатин) therefore the risk of development of a rabdomioliz increases.

At use of a klaritromitsin and omeprazol increase in Cmax, AUC and T1/2 of an omeprazol by 30%, 89% and 34% respectively is possible. Average value рН in a stomach during 24 h made 5.2 at reception only an omeprazol and 5.7 at reception of an omeprazol together with klaritromitsiny.

At use of a klaritromitsin and indirect anticoagulants strengthening of action of the last is possible.

At use of a klaritromitsin with sildenafily, tadalafily or vardenafily (FDE5 inhibitors), increase in the inhibiting impact on FDE is possible. The dose decline of FDE5 inhibitors can be required.

At joint purpose of a klaritromitsin with theophylline and carbamazepine increase in concentration of the last in a system blood-groove is possible.

At use of a klaritromitsin with tolterodiny at patients with slow metabolism through an isoenzyme of CYP2D6 the dose decline of a tolterodin can be required.

At joint reception of a klaritromitsin (1 g/days) with midazolam increase in AUC of a milazolam by 7 times is (orally) possible. It is necessary to avoid joint oral administration of a klaritromitsin and midazolam and other benzodiazepines which are metabolized by CYP3A isoenzyme (triazoles and alprazola). At use of midazolam (in/in) and the klaritromitsina can be required dose adjustment. The same precautionary measures should be applied also to other benzodiazepines which metabilizirutsya by CYP3A isoenzymes. For benzodiazepines which removal does not depend on CYP3A isoenzymes (temazepam, nitrazepam, lorazepam) clinically significant interaction with klaritromitsiny is improbable.

At reception of a klaritromitsin with colchicine strengthening of effect of colchicine is possible. Control of possible development of clinical symptoms of intoxication by colchicine, especially at elderly patients and patients with HPN is necessary (it was reported about cases with a lethal outcome).

At joint reception of a klaritromitsin and digoxin it is necessary to control carefully concentration of digoxin in serum (possibly increase in its concentration and development of potentially lethal arrhythmias).

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 at the same time orally, this interaction substantially manages to be avoided at reception of a klaritromitsin and zidovudine with an interval not less than 4 h.

At joint reception of a klaritromitsin (1 g/days) and an atazanavira (40 mg/days) increase in AUC of an atazanavir by 28%, a klaritromitsina twice, reduction of AUC of a 14-gidroksiklaritromitsin by 70% is possible. At patients with clearance of creatinine from 30 to 60 ml/min. the dose of a klaritromitsin should be lowered by 50%. Klaritromitsin in the doses exceeding 1 g/days it is impossible to appoint together with inhibitors of proteases.

At joint reception of a klaritromitsin and itrakonazol perhaps mutual increase in concentration of drugs in plasma. For the patients who are at the same time accepting итраконазол and кларитромицин careful observation because of possible strengthening or lengthening of pharmacological effects of these drugs is necessary.

At a concomitant use of a klaritromitsin (1 g/days) and a sakvinavira (in soft gelatin capsules, 1200 mg 3) increase in AUC and Css of a sakvinavir by 177% and 187% respectively, and a klaritromitsina for 40% is possible. At joint purpose of these drugs during limited time in the doses stated above dose adjustment is not required.

At joint reception with verapamil decrease in the ABP, a bradyarrhythmia and лактацидоз is possible.

Contraindications:

— porphyria;

— a concomitant use of an astemizol, a tsizaprid, Pimozidum, a terfenadin, ergotamine and other alkaloids of an ergot, midazolam for intake, an alprazolama, a triazolama;

— heavy chronic renal failure (KK less than 30 ml/min.);

— deficit of invertase/isomaltase, intolerance of fructose, glyukozo-galaktozny malabsorption;

— lactation period;

— children's age up to 3 years;

— hypersensitivity to a klaritromitsin (including to other macroleads) and to other components of drug.

With care: a renal or liver failure, gravis myasthenia, a concomitant use of the medicines which are metabolized a liver, a concomitant use of colchicine, pregnancy.

 

Use of the drug KLARITROSIN® at pregnancy and feeding by a breast
Use of drug at pregnancy and in the period of a lactation perhaps only in that case when the estimated advantage for mother exceeds potential risk for a fruit.

Klaritromitsin is allocated with breast milk therefore in need of purpose of drug in the period of a lactation it is necessary to stop breastfeeding.

 

Use at abnormal liver functions
It is contraindicated at heavy abnormal liver functions.

 

Use at renal failures
Patients with a chronic renal failure at clearance of creatinine have less than 30 ml/min. or with the content of serumal creatinine more than 290 µmol/l (3.3 mg / 100 the ml) a dose should be reduced twice or to double an interval between receptions. The maximum duration of treatment at patients of this group - 14 days.

It is contraindicated at heavy renal failures.

 

Use for children
To children from 3 to 12 years кларитромицин appoint in the daily dose 15 mg/kg divided into 2 receptions within 10 days. The maximum daily dose - 1 g.

Overdose:

Symptoms: nausea, vomiting, diarrhea, abdominal pain, confusion of consciousness.

Treatment: it is necessary to wash out immediately a stomach and to appoint symptomatic therapy. Is not removed at a hemodialysis and peritoneal dialysis.

Storage conditions:

Drug should be stored in dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

5 - planimetric strip packagings (1) - packs cardboard.
5 - planimetric strip packagings (2) - packs cardboard.
10 - planimetric strip packagings (1) - packs cardboard.
10 - planimetric strip packagings (2) - packs cardboard.